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The objective of this study is to address the unanswered question whether sustained supersaturation generated from amorphous solid dispersions (ASDs) formulated in insoluble hydrogel carriers will result in better bioavailability over that of spring-and-parachute type of dissolution profiles of ASDs formulated in water-soluble carriers. This was achieved by investigating the effects of supersaturation generation rates and doses on the extent of absorption (i.e., AUC) of Fenofibrate (FNB), a poorly-soluble model drug, from ASDs based on crosslinked poly(2-hydroxyethyl methacrylate) (PHEMA), physically crosslinked poly(vinyl alcohol) (PVA), and polyvinylpyrrolidone (PVP) in a rat model. Absorption modeling was conducted using GastroPlus® 9.7 to evaluate in vivo dissolution and absorption characteristics of FNB from these ASDs. The results show that the extent of FNB absorption from the rapid dissolution-controlled supersaturation build-up of PVP ASD was comparable to that of the gradual diffusion-controlled supersaturation generation from more hydrophilic PVA ASD; but both were higher than that of the less hydrophilic PHEMA ASD. The results also show that a moderate decrease in supersaturation rate is beneficial to the absorption of FNB. Moreover, this study confirms it is indeed possible to obtain similar exposure with lower doses of FNB when ASD formulations are employed as strategies for bioavailability enhancement., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ping I. Lee reports financial support was provided by Natural Sciences and Engineering Research Council of Canada. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Lipid nanoparticles (LNPs) have demonstrated their therapeutic potential as safe and effective drug delivery systems for nucleic acids during the COVID-19 pandemic. However, one of the main challenges during technical CMC (Chemistry, Manufacturing, and Controls) development is their long-term stability at temperatures of 2-8 °C or higher, which may be improved by the removal of water by lyophilization. In this study, we identified lyo-/cryo-protectants for freeze-dried mRNA-LNP formulations beyond conventional excipients such as sucrose and trehalose as T g -modifiers using polyA as a surrogate. Hydroxypropyl-beta-cyclodextrin, Kollidon® 12 PF (PVP), and dextran 40 kDa were tested in combinations to best stabilize the mRNA-LNPs during the lyophilization process as well as during storage for up to 6 months at 2-8 °C, 25 °C/60 % r.h., and 40 °C/75 % r.h.. We also tested the formulation principle including protectants in- and outside of the LNPs. Formulations were assessed for size, PDI, encapsulation efficiency, and properties related to the lyophilized dosage form. While 10 % (w/V) sucrose formulations successfully stabilized LNPs during the lyophilization process, they were not suitable for storage at temperatures beyond 2-8 °C. The most promising formulations for storage at higher temperatures were identified as 9 % (w/V) trehalose + 1 % (w/V) PVP with only a small increase in size over 6 months at 25 °C maintaining PDI and encapsulation efficiency. Results were verified with eGFP-mRNA-LNPs and tested in cell culture experiments. This study may serve as guidance for formulation scientists to further optimize freeze-dried mRNA-LNP formulations and eventually eliminate the cold chain for mRNA-LNP products., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved.)

Salt formation has been extensively used to modulate and improve the properties of active pharmaceutical ingredients (API), such as solubility, stability and mechanical properties. Tablets of the anti-angina drug, trimetazidine (TMZ) are currently manufactured using the wet granulation process, rather than the more cost-effective direct compression method. In an effort to address the two main challenges associated with the commercial dihydrochloride salt (TMZ-2HCl), i.e., poor flowability and high hygroscopicity, we have screened and prepared three new oxalate (Oxa) salts of TMZ, i.e., TMZ:Oxa 2:1 (hemi-salt), 1:1 (mono-salt), and 1:2 (di-salt). All of the three salts exhibited improved solid-state properties over TMZ-2HCl, including flow, tabletability, and stability against high humidity. Among the three salts, the TMZ-Oxa (1:2) di-salt demonstrates overall superior properties, establishing it as the most promising alternative crystal form. Consequently, using the di-salt, we developed a direct compression tablet formulation that shows potential for commercial manufacturing., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier B.V.)

Synchronising both cocrystal dissolution and drug precipitation processes is the key for the development of cocrystal systems with desired dissolution-supersaturation-precipitation (DSP) behaviours. Our findings with ketoconazole (KTZ) - p-aminobenzoic acid (PABA) 1:1 cocrystal show that this can be achieved by generating non-stoichiometric coformer concentrations that allow us to modulate the maximum theoretical cocrystal supersaturation SA (thermodynamic limit) below the drug critical supersaturation σ crit (kinetic limit). The application of our conceptual graphical approach combined with the two metrics SA and the DSP index answer the question of how much additional coformer is needed to target optimal sustained drug supersaturation levels. Modulating SA < σ crit and DSP index  > 1 allowed for a stable and sustained KTZ release system with supersaturation levels of 6 by 24 h. Findings provide a direct approach for better early decisions regarding cocrystal dose design and/or coformer concentration to be added to formulations to ultimately fine-tune drug supersaturation by coupling dissolution and precipitation processes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2025. Published by Elsevier B.V. All rights reserved.)

The pharmaceutical industry is striving to develop innovative and promising tools, increasingly embracing new data-driven approaches, to understand, improve and accelerate the drug product development process. While extended release (ER) oral formulations offer a number of advantages, including maintenance of therapeutic drug levels, a reduction in dosing frequency, and minimization of side effects, achieving consistent drug release profiles remains a significant challenge. As a critical attribute for drug absorption into systemic circulation, in vitro dissolution testing represents a time-consuming and complex method for the evaluation of such formulations. The main objective of this study was to develop a model for predicting drug dissolution in the quality by design (QbD)-based development of ER oral hydrophilic matrix tablets comprising polyethylene oxide (PEO). Two main modeling approaches are conducted and compared: (i) model screening to fit and compare multiple predictive machine learning (ML) models and then deploy the best model, in this case, artificial neural networks (ANN), and (ii) functional data analysis (FDA) combined with the design of experiments (DoE) that fit a smoothing model to each dissolution curve as a continuous function. A dataset comprising 91 ER matrix tablet formulations was analyzed, with the dissolution data split into training, validation, and test sets (70%, 20%, and 10%, respectively). The results demonstrated that both ANN and functional DoE (FDOE) models achieved high similarity with the experimental dissolution profiles, as indicated by f2 values ranging from 48 to 88 for the FDOE and 52 to 88 for ANN. This work highlights the potential of integrating advanced data-driven modeling techniques into ER drug development to enhance dissolution prediction accuracy and streamline the formulation process, thus reducing time and costs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved.)

In recent years, deep eutectic solvents (DESs) with their outstanding solubilization properties have emerged as strong candidates for oral enabling formulations of poorly soluble drugs. This study explores the use of drug-based therapeutic DESs (THEDESs) to solubilize a poorly soluble compound with the aim of providing a fixed-dose combination of two complementary therapeutic agents. Specifically, potential anticancer effects of ibuprofen (IBU) are harnessed in a novel type of THEDES to dissolve higher amounts of abiraterone acetate (AbAc), an antitumor agent. Four IBU-based combinations were studied: 1:4 M ratio with octanoic acid (OctA), 1:5 with nonanoic acid (NonA), 1:3 with decanoic acid (DeA) or 1:2 with dodecanoic acid (DoA). Fatty acids of different chain lengths were analyzed and discussed considering surface charge densities obtained via quantum chemistry. The THEDESs listed could apparently dissolve AbAc amounts up to 1311.0 ± 125.4 mg/g in IBU:OctA THEDES, 1151.7 ± 22.2 mg/g in IBU:NonA, 1160.4 ± 33.5 mg/g in IBU:DeA, and 231.3 ± 10.7 mg/g in IBU:DoA. In vitro dissolution of the simultaneously released drugs reached 37.8 ± 9.0 % to 64.2 ± 1.0 % for IBU and 5.0 ± 3.3 % to 19.4 ± 0.1 % for AbAc. This increased to between 60.4 ± 2.8 % and 79.4 ± 5.0 % of released IBU, and 23.6 ± 1.0 % to 57.3 ± 5.8 % of released AbAc, with 20 % (w/w) Tween 80 added to the formulations. This showed the significant potential of drug-containing THEDESs as solubilizing agents for poorly soluble drugs, in the form of fixed-dose combinations of synergistic APIs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved.)

In recent years, CM has become increasingly popular in the pharmaceutical industry for the production of OSD forms. Most of the newly developed APIs nowadays are extremely cohesive and sticky with a mean particle size particle of <100 μm, a wide PSD and a high tendency to agglomerate, making them difficult to accurately dose using loss-in-weight equipment during CM. In this research paper, the effect of various glidants on the volumetric and gravimetric feeding of several APIs was assessed. Three challenging API (APAPμ, MPT and SD) and four different glidants (Aerosil® 200, Aerosil® R972, Syloid® 244FP and TRI-CAFOS® 200-7) were selected. For all feeding trials, a GEA CF equipped with 20 mm concave screws was used, in combination with an external catch scale. The volumetric feeding trials showed the ability of each glidant to increase the FF max and reduce the FF movRSD40 and the FF decay for the cohesive APIs (APAPμ and MPT). Although the fumed silica grades showed the highest impact on the previously mentioned feeding parameters, low AE10 values were obtained, negatively affecting the feeding performance at higher glidant concentration. Both Syloid 244FP and TCP were good alternatives. However, to obtain a similar feeding performance a higher concentration of these glidants is required. The volumetric trials showed that glidant addition has no additional benefits for APIs with good flow properties such as SD. The second part of this paper discussed the impact of glidant addition on the gravimetric feeding behavior of the cohesive powders. Both the fumed silica grades (Aerosil® 200 and Aerosil® R972) and Syloid 244FP lowered the deviation on all LC% profiles of the cohesive APIs. In contrast to the volumetric trails, blends with excess fumed silica resulted in low AE10 values which are efficiently dosed by the CF during the gravimetric feeding., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Several contributors of Johnson & Johnson contributed to the paper and can be found in the affiliation. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Micronization is frequently employed to increase the dissolution of poorly soluble drugs, but it easily led to powder aggregation and difficult to mix well on the micro level with poor content uniformity and erratic dissolution behavior. Mannitol is the most commonly used pharmaceutical excipient, and its β form (β-mannitol) is commercially available and extensively investigated, whereas form α (α-mannitol) remain poorly understood. Here, this study demonstrated that α-mannitol could significantly eliminate aggregation phenomena of micronized drugs (i.e., lurasidone hydrochloride, indomethacin and ibuprofen) after general mixing, while β-mannitol could not. In addition, the drug dissolutions after mixing with α-mannitol were also significantly higher than that with β one. This stemmed from the different molecular orientation on their dominant crystal facets, resulting in greater number of unsaturated hydrogen bonds site (0.050 Å -2 vs 0.042 Å -2 ) on α-mannitol's crystal facet {013}, leading to more positive charge and negative charge site and higher surface energy (64.42 mJ/m 2 vs 50.26mJ/m 2 ). Subsequently, this increased the interaction between drug and α-mannitol, which is higher than interaction between drug itself, also higher than interaction between drug and β-mannitol, resulting in adhesion of drug powder on α-mannitol rather than cohesion into aggregates. Moreover, after 30 days of storage at 60 °C or 92.5 % relative humidity, the polymorphic purity of α-mannitol remained above 99 %, indicating good polymorphic stability during transportation and storage. This work illustrates that α-mannitol exhibited great potential to serve as a new pharmaceutical excipient in solid dosage forms. We believe that utilizing the benefits of polymorphism and mitigating their limitations will exert great potential for the development of functional pharmaceutical excipients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier B.V. All rights reserved.)

For monoclonal antibody drug products as for other biologics, while the innovator drug products first becomes commercially available, they are often followed by one or more biosimilar products. These biosimilars often differ from the innovator product, as well as from each other, in their formulation composition. However, the impact of the formulation composition on the stability of the active pharmaceutical ingredient subjected to different 'stresses' is still not understood. We have evaluated the effect of different formulations on structural stability and aggregation behavior of a monoclonal antibody, trastuzumab (both the drug substance and the final drug product), against three most common stresses encountered during production, storage, and formulation into a lyophilized product - freeze-thaw, freeze-drying, and agitation. Irrespective of the stabilizer used, the formulations exhibited good conformational stability against all three stresses. However, the freeze-drying process caused a significant increase in the number of soluble aggregates, but only in sucrose containing formulations. On the other hand, agitation in sorbitol containing formulation led to a significant increase in insoluble aggregates. This effect could also be attributed to the absence of surfactant in this formulation composition. The stabilizing effect of trehalose appeared to be independent of its concentration. Therefore, the effect of formulation composition is more pronounced for aggregation of trastuzumab than for its conformational stability. Our findings suggest that formulation design warrants consideration of both conformational stability and aggregation behavior of the active ingredient., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Raj Suryanarayanan reports financial support was provided by US Food and Drug Administration. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.]., (Copyright © 2025. Published by Elsevier B.V.)

Amorphous solid dispersions (ASDs) are widely recognized for their potential to enhance the solubility of poorly water-soluble drugs, with factors such as molecular mobility, intermolecular interactions, and storage conditions playing critical roles in their performance. However, the influence of preparation methods on their performance remains underexplored, especially regarding their supersaturation . To address this gap, the present study systematically investigates ASDs of ibuprofen (IBU, used as a model drug) prepared using two widely utilized techniques (solvent evaporation, SE, and melt-quench cooling, M-QC). Three different matrices/carriers (Soluplus®, SOL, povidone, PVP, and copovidone, PVPVA) were employed to evaluate the combined influence of preparation method, matrix/carrier type, and drug loading on ASD performance. Supersaturation behavior during dissolution, particularly its dependence on the Sink Index (SI), was a key focus. All ASDs showed successful amorphization, but molecular near-order structures differed based on the preparation method. ATR-FTIR spectroscopy revealed stronger molecular interactions in M-QC ASDs (compared to SE). Dissolution studies under supersaturation conditions (SI = 0.1 and SI = 0.2) highlighted significant performance differences. M-QC ASDs consistently exhibited higher in vitro AUC (0→t) values under non-sink conditions compared to crystalline IBU. Conversely, SE ASDs showed improved supersaturation primarily under low SI conditions, especially with SOL at low drug loadings. The findings underscore the need for a systematic approach in developing ASDs, considering preparation method, matrix/carrier type, drug loading and dissolution study conditions collectively. These factors significantly influence dissolution behavior and supersaturation, emphasizing that they should not be independently studied but evaluated comprehensively to optimize ASD performance., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Up-scaling on a rotary tablet press by increasing turret speed can have a negative effect on die filling performance, as the dies have less time to be filled, leading to high tablet weight variability. For this reason, double-tip tooling is investigated, where a punch contains 2 tips instead of 1, doubling the throughput without the need to increase turret speed. However, when using multi-tip punches, one has to bear in mind that punch responses, e.g. pre- and main compression force, are the sum of each tip. When using these responses to assess tablet properties during compression, it is assumed that they can be divided over the total number of punch tips, i.e. an equal contribution of each tip to the response. This assumption can only hold when die filling is uniform across all tips. In this work, the impact of formulation material properties and process settings (X) upon die filling performance for double-tip tooling (Y) was studied, by developing and analyzing a PLS model regressing X versus Y. Additionally, this model enables the estimation of die filling variability based on material characterization data, eliminating the need for extensive tableting experiments and reducing material consumption in R&D., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Nowadays, most of the newly developed active pharmaceutical ingredients (APIs) consist of cohesive particles with a mean particle size of <100μm, a wide particle size distribution (PSD) and a tendency to agglomerate, therefore they are difficult to handle in continuous manufacturing (CM) lines. The current paper focuses on the impact of various glidants on the bulk properties of difficult-to-handle APIs. Three challenging powders were included: two extremely cohesive APIs (acetaminophen micronized (APAPμ) and metoprolol tartrate (MPT)) which previously have shown processing issues during different stages of the continuous direct compression (CDC)-line and a spray dried placebo (SD) powder containing hydroxypropylmethyl cellulose (HPMC), known for its sub-optimal flow with a high specific surface area (SSA) and low density. Four flow-enhancing excipients were used: a hydrophilic (Aerosil® 200) and hydrophobic (Aerosil® R972) fumed silica grade, a mesoporous silica grade (Syloid® 244FP), and a calcium phosphate excipient (TRI-CAFOS® 200-7). The APIs and binary API/glidant blends (varied between 0.5-2.75 w/w%) were characterized for their bulk properties relevant for CDC. The results indicated that optimizing different bulk parameters (e.g., density, flow, compressibility..) of an API required varying weight percentages of the glidant (e.g., different surface area coverage (SAC)) depending on the APIs. Moreover, even at similar SAC, the impact of the glidant on the bulk characteristic of the APIs depended on the glidant type properties. While nano-sized silicon dioxide were effective for improving the flowability of a powder, other glidants (mesoporous silica and tricalcium phosphate (TCP)) showed also promise as alternatives. Additionally, an excess of glidant, referred to as oversilication, negatively impacted some bulk parameters, but other characteristics were unaffected. Finally, to determine the appropriate concentration of the different classes of glidants, SAC calculations, an understanding of the glidant's working mechanism, and knowledge about the API's characteristics (i.e., morphology, compressibility, flowability, aeration, density, and wall friction) are required. This study confirmed the necessity of including various material characterization techniques to assess the impact of glidants on the bulk characteristics of APIs., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Several contributors of Johnson & Johnson contributed to the paper and can be found in the affiliation. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Oral drug delivery remains the preferred method of drug administration but due to poor solubility many active pharmaceutical ingredients (APIs) are ill suited to this. A number of methods to improve solubility of poorly soluble Biopharmaceutical Classification System (BCS) Class II drugs already exist but there is a lack of scalable, flexible methods. As such the current study applies the innovative technique of aerosol jet printing to increase the dissolution capabilities of a Class II drug in a manner which permits flexibility to allow dosage form tailoring. Aerosol jet printing provided a high degree of control allowing effective scaling, by size and layering, and control over drug distribution. Aerosol jet printing of pure active pharmaceutical ingredient (fenofibrate) resulted in crystalline material but as polymer excipient content was increased, morphological changes occurred and a fully amorphous product was generated on inclusion of 75 % (w/w solute) polymer content or above. This amorphous product has been found to exhibit a 10-fold increase in drug dissolution relative to comparable physical mixtures. In conclusion, aerosol jet printing is a novel and effective, scalable method providing improved dissolution coupled with high spatial precision and warrants further investigation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Author(s). Published by Elsevier B.V. All rights reserved.)

Solid forms transformations and new crystal structures of an active pharmaceutical ingredient (API) can occur due to various manufacturing process conditions, especially if the drug substance is formulated as a hydrate. The conversion between hydrate and anhydrate forms caused by changes in temperature and humidity must be evaluated because of the risk of dehydration and phase transitions during the manufacturing process. Differences in physicochemical, mechanical, and rheological properties have been observed between solid forms of the same API that can cause manufacturing and product-related issues. Atorvastatin calcium trihydrate (ACT) is a synthetic lipid-lowering agent that was discovered during Lipitor® (its anhydrous form) Phase 3 clinical trials after passing Phase I and II. This case highlights the importance of routinely performing solid form screenings because of the probability of finding new solid forms during the development and scale-up process. Therefore, in this contribution, ACT tablet formulation was performed and evaluated starting from the compatibility of 1:1 proportions of drug and the excipients microcrystalline cellulose 101 (MCC 101), calcium carbonate, lactose monohydrate, croscarmellose sodium, hydroxypropyl cellulose, magnesium stearate, and polysorbate 80. Then, 40 mg ACT tablets were prepared on a small pilot scale, and manufacturing process assessment was conducted by sampling process stages selected as critically prone to solid forms formation or phase transition. Final product quality was evaluated regarding weight variation, hardness, disintegration, dissolution, and assay tests. Powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA) were applied to solid state evaluation. The starting raw material was confirmed to be ACT Form I. From the preformulation studies, PXRD, FT-IR and TGA analyses showed no interactions between ACT and excipients, while DSC results revealed a physical interaction with MCC 101, not considered an incompatibility. The effect of the tablet manufacturing process was achieved by amorphization, while some ACT long-range crystalline structure remained, as confirmed by PXRD, FT-IR and DSC. However, the tablets' quality parameters were found to be within the acceptable range of both the pharmacopeia guidelines and manufacturer parameters regarding weight variation, hardness, disintegration, dissolution, and assay tests., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Salazar-Barrantes et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Retrosynthesis is a strategy to analyze the synthetic routes for target molecules in medicinal chemistry. However, traditional retrosynthesis predictions performed by chemists and rule-based expert systems struggle to adapt to the vast chemical space of real-world scenarios. Artificial intelligence (AI) has revolutionized retrosynthesis prediction in recent decades, significantly increasing the accuracy and diversity of predictions for target compounds. Single-step AI-driven retrosynthesis models can be generalized into three types based on their dependence on predefined reaction templates (template-based, semitemplate-based methods, template-free models), with respective advantages and limitations, and common challenges that limit their medicinal chemistry applications. Moreover, there are relatively inadequate multi-step retrosynthesis methods, which lack strong links with single-step methods. Herein, we review the recent advancements in AI applications for retrosynthesis prediction by summarizing related techniques and the landscape of current representative retrosynthesis models and propose feasible solutions to tackle existing problems and outline future directions in this field.

Purpose: This work reports the development and characterisation of polymeric films composed of gelatin or its chemically modified derivatives (crotonoylated, itaconoylated, and methacryloylated gelatins) blended with polyvinyl alcohol (PVA). Metronidazole served as an antimicrobial drug in these formulations., Methods: The films were produced by casting aqueous solutions of polymers, followed by solvent evaporation. Their structure and physicochemical characteristics were studied using Fourier transform infrared spectroscopy, scanning electron microscopy, and mechanical testing. The thickness of the films, their folding endurance, the surface pH, and transparency were also evaluated. The mucoadhesive performance of the films was evaluated through an ex vivo detachment technique involving freshly excised sheep vaginal tissues. In vitro cumulative drug release studies were conducted using Franz diffusion cells., Results: The results demonstrate that incorporating unsaturated functional groups into gelatin improves its mucoadhesive properties compared to native gelatin. The drug release experiments conducted in vitro showed that the cumulative release from pure gelatin/PVA films was found to be 49 ± 2%, whereas modified gelatins/PVA (70:30) films released ~ 64-71%., Conclusion: These findings suggest that modified gelatins could serve as effective excipients in designing mucoadhesive formulations for vaginal administration, with potential applications extending to other transmucosal drug delivery systems., Competing Interests: Declarations. AI technology was used to refine language. Conflict of Interest: The authors declare no conflicts of interest in relation to the work presented in this paper., (© 2025. The Author(s).)

Capecitabine, an oral prodrug of 5-fluorouracil, is increasingly being loaded into various drug delivery system to enhance its bioavailability and cytotoxicity. This study aimed to prepare and evaluate capecitabine-loaded niosomes as a drug delivery system for breast cancer treatment. The niosomes were prepared by thin film hydration method using Span 60 and cholesterol. Optimization was done using 3 2 factorial design with the responses of particle size and entrapment efficiency. Scanning electron microscopy (SEM) was used to observe the morphology. Fourier transform infrared spectroscopy (FTIR) and ultraviolet (UV) spectrophotometry were used to confirm the nature of the interactions. The optimized batch was further assessed for percent cumulative drug release, nature of crystallinity using the X-ray diffraction method, and drug excipient compatibility using FTIR and Differential Scanning Calorimetry (DSC). The optimized batch (F8) exhibited a particle size of 118 nm, a zeta potential of 24.1 mV, an entrapment efficiency of 93%, and a polydispersibility index (PDI) of 0.25. The cumulative drug release in a pH of 6.8 indicated that 86.46 ± 0.45% of the drug was released in 24 h. Cytotoxicity testing using MTT assay on MCF-7 breast cancer cell lines showed that the capecitabine niosomes were 2.6 times more cytotoxic than the pure drug. The study demonstrates that capecitabine-niosomes significantly enhanced the anticancer activity of capecitabine, suggesting a promising approach for breast cancer treatment., Competing Interests: Declarations. Conflict of Interest: The authors declare that they have no conflict of interest., (© 2025. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Study explored the synergistic anti-tumor effects of a combination of compounds from Traditional Chinese Medicine, including rosmarinic acid (RA), chlorogenic acid (CA), and scoparone (SCO), in the formulation of multivesicular liposomes (MVLs). Optimization of formulations and process parameters was essential to achieve effective liposomal encapsulation and optimal release profiles for these three compounds with diverse properties. Traditional trial-and-error approaches are inefficient for the optimization of complex multi-compound MVLs. We developed a new formulation optimization model, which could address this issue by predicting the optimal multi-compound MVLs formulation. Our machine learning model integrated support vector machine regression (SVR) algorithm and cuckoo search (CS) algorithm, resulting in three CS-SVR models to predict single-compound MVLs. The CS algorithm, with various weighting rules, was then applied to search the best formulation parameters across three CS-SVR models and to maximize the encapsulation efficiency for all three compounds. The multi-compound MLVs were subsequently prepared under the predicted conditions, achieving an optimized particle size of 15.12 µm, with encapsulation efficiencies of 82.93 ± 2.43% for CA, 82.22 ± 1.25% for RA, and 95.60 ± 0.18% for SCO. The predicted optimal multi-compound MVLs were further validated through in vitro characterization and in vivo anti-tumor experiments, showing a promising synergistic anti-tumor effect consistent with in vitro results. This model accurately predicted optimal encapsulation conditions, which were validated experimentally, demonstrating improved encapsulation efficiencies and reduced trial-and-error iterations. Collectively, our model provides a predictive pathway for multi-compound MVLs formulation, indicating the ability of this model to significantly reduce experimental burden and accelerate formulation development., Competing Interests: Declarations. Conflict of Interest: The authors state no conflict of interest., (© 2025. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Gefitinib (GB), an oral tyrosine kinase inhibitor suffers major setbacks in clinical application due to limited aqueous solubility leading to poor oral bioavailability. Nanosuspension serves as a promising formulation strategy to overcome the above-mentioned drawbacks. Hence, the present study involves the development of gefitinib nanosuspension (GB-NS) using High-pressure homogenization (HPH) to increase its aqueous solubility and maximize oral bioavailability. GB-NS was optimized by utilizing the quality-by-design strategy to optimize independent variables such as homogenization pressure, drug-to-stabilizer ratio, and number of cycles. Lecithin was found to stabilize the nanosuspension with optimal particle size, PDI, and zeta potential of 157 ± 18.77 nm, 0.296 ± 0.040, and -33.25 respectively. Intriguingly, a drug-to-stabilizer ratio significantly influenced (p < 0.005) particle size and PDI, establishing its crucial role in optimization. The morphological characterization by SEM of GB-NS revealed a rod-shaped structure. Thereafter, the thermal and powder X-ray analysis depicted the crystalline nature of gefitinib in GB-NS. Additionally, GB-NS exhibited enhanced saturation solubility (~ 2.4- and ~ 3.4-fold) and dissolution rate (~ 2.5- and ~ 3.5-fold) compared to pure GB in 0.1 N HCl and PBS 6.8 respectively. GB-NS remained stable under both storage conditions ( 25°C and 4°C). Finally, the pharmacokinetic study depicted a considerable increase in C max (~ 2.84-fold) and AUC (0-t) (~ 3.87-fold) of GB-NS when compared to free GB. Therefore, developed formulations showed a competent solution for enhancing the oral bioavailability of poor water-soluble drugs., Competing Interests: Declarations. Conflict of Interest: The authors declare no financial competing interest., (© 2025. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Interest in oral delivery of biological drug products, commonly prepared through lyophilization, is surging. Typically, low solid content solutions are employed for lyophilization to enhance mass transfer and minimize drying time. Yet, this approach often results in lyophilized powders with low bulk density and poor flowability, challenging downstream processing steps that are required for oral product development. Increasing solid content in a starting solution can, in theory, increase the density of lyophilized cakes and powders post-milling. However, the effectiveness of improving powder density and flowability using a higher solid content has not been experimentally verified. In addition, the impact of using a higher solid content on other physicochemical properties of lyophilized materials remains uncertain. To address the knowledge gaps, we lyophilized three common bulk cryoprotectants at two different solid contents (5% and 10%) and systematically evaluated their solid-state properties, bulk density, flowability, compaction characteristics, and physical stability. We found that powders prepared at a higher solid content (10%) exhibited higher bulk density, but they still failed to meet the requirements for easy oral product development. A change in solid content also leads todistinct solid-state properties, compaction behaviors, and stability, highlighting the importance of thorough characterization of lyophilized materials when solid content is changed in the course of oral solid dosage formulation development., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ketorolac, a nonsteroidal anti-inflammatory drug, exhibits moderate antipyretic and anti-inflammatory properties, as well as potent analgesic effects. It is widely used in clinical practice for pain relief in cases of mild and severe pain such as postoperative pain, fractures, sprains, toothaches and cancer pain. Due to its relatively short half-life, patients experiencing pain often need frequent injections or oral medications, leading to poor patient compliance. Thus, it is crucial to create long-acting sustained-release formulations of ketorolac. This paper provides an overview of the research, applications, and challenges associated with ketorolac sustained-release formulations over the past decade, based on a comprehensive review of the literature. The aim is to provide fresh insights for the research and development of long-acting, sustained-release, and controlled-release formulations of ketorolac., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier B.V. All rights reserved.)

This study investigates the effect of silanol density on the surface of glass containers on the stability of monoclonal antibody (mAb) formulations subjected to mechanical stress. By calcining Type I glass containers at different temperatures, we altered the concentration of silanols on the glass surface and examined its impact on the stability of protein formulations under mechanical stress. Contact angle measurements and Fourier Transform Infrared (FTIR) spectroscopy indicated that silanol formation influences the hydrophilicity of the surface. Additionally, mAb solutions filled in Type I glass containers with varying silanol densities were repeatedly dropped from a height of 0.5 m to simulate mechanical stress during transport. The results demonstrated that increasing surface silanol density reduces protein monomer loss and the formation of protein aggregates and subvisible particles. Furthermore, protein aggregates and subvisible particles formed by dropping did not activate the complement in human serum in vitro. Adjusting the silanol density on the glass container surface offers an economical and environmentally friendly approach to improving the stability of mAb formulations during transportation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Conventional drug formulations release active pharmaceutical ingredients (APIs) immediately after administration, while long-acting (LA) drug products are designed for prolonged therapeutic effects, thereby reducing administration frequency and improving patient compliance. The development of LA therapeutics for chronic disease treatment has significantly helped patients adhere to their regimens, reducing the need for daily doses and easing the burden on healthcare systems. Advances in treatment have transformed Human Immunodeficiency Virus (HIV) into a manageable chronic disease, and efforts are underway to eliminate HIV in the future. Nowadays, antiretroviral therapies (ARTs) are widely available and accessible, daily oral pre-exposure prophylaxis (PrEP) has been highly effective and the new LA ARTs and LA PrEP are being actively pursued. The development of LA antiretrovirals for HIV has revolutionized the landscape of global implementation of HIV prevention and treatment. This article provides an overview of LA medicines (pills, injections, solid implants, and in situ forming depots) for the prevention and treatment of HIV from a pharmaceutics perspective, describing approved medicines, recognizing promising technologies, and discussing the pros and cons of poly (lactic-co-glycolic acid) (PLGA) particles, liposomes, hydrogels, and organogel formulations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Enhancing the aqueous solubility via amorphization of crystalline poor glass-forming drugs represents a challenge, particularly when drug dosing is high. In such scenarios, there is often a need for high polymer loadings, leading to an increase in the dosage form mass and less patient acceptability. This work investigated the role that polymer type and after-melt cooling rate had upon the amorphicity of solid dispersions (SDs) containing high levels of naproxen and three commonly used polymeric excipients: Eudragit® EPO, Kollidon® VA64, and Soluplus®. Using a combination of thermogravimetry, conventional and fast-scan DSC, oscillatory rheology, in silico Hansen solubility parameter computation, FTIR, and PXRD, we have shown that amorphicity could be affected by the cooling rate with the specific polymer type and amount playing a significant role in the degree of this impact. The amorphous drug content, evident at higher cooling rates, was found to be dependent on drug-polymer interaction and polymer melt viscosity. Higher polymer concentration and faster cooling produced less melt crystallization upon cooling, which was attributed to a shift in nucleation to lower temperatures where it could be inhibited by polymer matrix viscosity. Amorphous drug content, which contained drug nuclei, was evidenced by cold crystallization upon reheating. After 4 weeks of 'gentle' storage, cold crystallization increased if nucleation was the dominant process, whereas cold crystallization decreased if crystal growth prevailed. Storage at elevated temperature and humidity resulted in the absence of cold crystallization, and increased melt crystallisation. Thus, faster cooling could serve as an additional tool to improve amorphous yield and stability of high drug-loaded SDs, however, intermolecular polymer-drug interaction, melt viscosity of the drug-polymer matrix, and storage conditions are of critical importance to achieve this goal., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

In the realm of therapeutic antibodies, co-formulations comprising two or more monoclonal antibodies (mAbs) have emerged as a promising strategy, offering enhanced treatment efficacy, improved efficiency, and prolonged intellectual property protection. These advantages have sparked significant interest among both patients and pharmaceutical companies. However, the quantification and analysis of individual mAbs within such co-formulations pose a substantial challenge due to their similar physicochemical properties. To address this challenge, we introduce a pH gradient cation exchange chromatography (CEX) method designed to effectively separate three mAbs that share significant similarities in molecular weight, structure, and isoelectric points (pIs) etc. This versatile approach not only facilitates the accurate quantification of each mAb's concentration and their respective ratios within the co-formulation, but also allows for the comprehensive characterization of all charge variants present. In the case of a co-formulation containing three antibodies, the developed CEX method demonstrated superior performance compared to other techniques. The method's robustness was further underscored by its qualification parameters, including acceptable precision (RSD ≤ 3 %), accuracy (95 %-115 % recovery), and linearity (R 2  > 0.99) across a range of 10 to 30 μg load for each mAb. Moreover, the method has been successfully applied in stability studies to quantitatively analyze individual mAb concentrations within co-formulations, marking a significant advancement in the field. Through this work, we contribute a crucial analytical insight into mAb co-formulations, especially those comprising three or more molecules, underscoring its considerable potential to propel the field of biotherapeutic co-formulations forward., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Pharmaceutical tablets are routinely film-coated to improve appearance, reduce medication errors and enhance storage stability. Terahertz pulsed imaging (TPI) can be utilised to study the liquid penetration into the porous tablet matrix in real time. Using polymer-coated flat-faced tablets with anhydrous lactose or mannitol, we show that when the tablet matrix contains anhydrous material, the anhydrous form transforms to the solid-state hydrate form in the tablet core while the immediate release coating dissolves. The process starts at the interface between the coating and the core. It commences inward for more than 7min, resulting in a shell of hydrate form on the order of a few hundred microns thicknesses immediately underneath the dissolving coating. TPI is sensitive enough to detect and spatially resolve this process based on the subtle change in the refractive index of the two materials. TPI can further resolve tablets with different components using the time-domain waveforms in reflection and provide insights into the presence of hydrate material (lactose monohydrate) in altering the water mass transport mechanism. The kinetics data obtained from TPI fit the power law model (y=kt m ), whose constants enable us to infer the different mass transport mechanisms., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Mingrui Ma reports financial support was provided by Cambridge Commonwealth European and International Trust. Mingrui Ma reports financial support was provided by CSC Chinese Scholarship Council. Member of the editorial board at IJParm - JAZ If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved.)

Favipiravir, a high dose antiviral drug effective for oral treatment for COVID-19, with poor water solubility is formulated using a simple, low-cost melt coating and granulation methodology. High-dose (82.5 % w/w API) tablets (600 mg and 800 mg) with desired release profiles are developed while minimizing excipient burden. First, twin-screw melt coating and granulation (MCG) of Favipiravir, using Poloxamer P188 as a binder as well as a surfactant, was utilized to create Favipiravir granules with high solubility and tabletability. These granules were then blended with a small amount of extra-granular ingredients (high molecular weight Hydroxypropylmethyl Cellulose and Magnesium Stearate) and compacted into tablets with desired controlled-release tablets. Results demonstrate that the application of MCG to coat and granulate a poorly soluble drug, using a low melting point surfactant as a binder and wetting agent, can be an effective approach to manufacture high-dose modified release formulations for low solubility drugs that are common in the treatment of infectious diseases, cancer, autoimmune diseases, and many other conditions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier B.V. All rights reserved.)

In this study, lyophilizates with the second-class antipsychotic agent lurasidone hydrochloride were developed as orodispersible platforms to improve patients' adherence. The primary aim was to evaluate the effect of the amino acid additive (L-arginine, L-lysine, L-histidine) and the freeze-drying stage on the pharmaceutical performance of the designed formulations. The composition was initially optimized using an experimental design approach. The amino acids (in particular L-histidine) acted as dispersing agents, prevented drug aggregation and assured high drug content uniformity within the lyophilizate matrix. The freeze-drying stage reduced the particles dimensions which significantly increased solubility of lurasidone hydrochloride, and consequently, it's dissolution rate. The presence of L-arginine in lyophilizate composition balanced out sufficient compression strength with a rapid drug release. Despite the fact that L-lysine enhanced the mechanical strength, it also caused delayed drug release. Notably, L-histidine and L-arginine accelerated transport of lurasidone hydrochloride through the porcine buccal epithelium with approximately 100% and 50% increase in absorption, respectively, when compared to commercial reference drug. Overall, the designed lyophilizates containing L-histidine and L-arginine, hold promise as orodispersible platforms for improved performance of lurasidone hydrochloride., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Buffer exchange is a critical step in biologics development, playing a pivotal role in removing contaminants, adjusting sample conditions, and facilitating compatibility studies. The efficiency of centrifugal concentrators for polysorbate removal was compared to a two-step approach involving a surfactant removal column followed by buffer exchange. Trastuzumab-pkrb from Herzuma® was used. While a 30 kDa centrifugal concentrator was ineffective in polysorbate removal, a 50 kDa concentrator caused partial removal. Surfactant removal column proved more effective in removing polysorbates. Buffer exchange using polysorbate-containing formulation buffer, even with a 50 kDa concentrator, accumulated polysorbate, revealing the need for a different approach in small-scale formulation. Adding polysorbate in a separate step after buffer exchange appeared to be a good strategy to prevent this problem. The two approaches did not reveal any differences in the protein aggregation behavior., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The coamorphous formulations have attracted increasing interest due to enhanced solubility and bioavailability, together with synergistic pharmacological effects. In this study, a ternary coamorphous system of polyphenols was successfully prepared, wherein baicalein (Bai) and resveratrol (Res) were constructed into a single-phase coamorphous system mediated by piperine (Pip). FTIR and ss 13 C NMR spectra together with quantum chemical calculation and molecular dynamics simulation suggested Pip as a molecular bridge connected Bai and Res molecules through π-π stacking and hydrogen bonding interactions. The configuration of coamorphous Bai-Pip-Res could minimize the system energy to facilitate its formation and enhance the stability. The ternary system showed 3.2, 4.3 and 5.3-fold increase in apparent solubilities of Bai, Res and Pip, and maintained the peak concentrations for at least 24 h. Compared to binary coamorphous systems, the ternary system exhibited superior physical stability under temperature and humidity conditions. Furthermore, coamorphous Bai-Pip-Res exhibited enhanced antibacterial activity, significant antioxidant ability and synergistic anti-inflammatory effect. This work offers a promising strategy to construct a ternary coamorphous delivery system with enhanced pharmaceutical properties by incorporating a molecular bridge, especially for components with the lack of intermolecular interactions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Numerous commercially available biopharmaceuticals are frozen or freeze-dried in vials. The temperature at which ice nucleates and its distribution across vials in a batch is critical to the design of freezing and freeze-drying processes. Here we study experimentally how the level of particulate impurities - a key parameter in pharmaceutical manufacturing - affects the ice nucleation behavior. Samples prepared under particulate-free conditions were found to nucleate at significantly lower temperatures and with more variability than samples of the same composition that were prepared under standard laboratory conditions, i.e., without using any means of lowering particulate counts. In contrast, spiking solutions with silver iodide particles resulted in significantly higher and less variable nucleation temperatures. These findings confirm that the level of particulates has a relevant effect on the rate of ice nucleation under conditions of industrial relevance. We further assessed the nucleation behavior of two biopharmaceuticals, a vaccine based on a viral vector and a mAb, and observed major differences in their nucleation behavior. This emphasizes the importance of measuring the ice nucleation behavior of biopharmaceuticals during process design., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Marco Mazzotti reports financial support was provided by The Janssen Pharmaceutical Companies of Johnson & Johnson. The other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved.)

Cosmetic inspection of freeze-dried products is an important part of the post-manufacturing quality control process. Traditionally done by human visual inspection, this method poses typical challenges and shortcomings that can be addressed with innovative techniques. While many cosmetic defects can occur, some are considered more critical than others as they can be harmful to the patient or affect the drug's efficacy. With the rise of artificial intelligence and computer vision technology, faster and more reproducible quality control is possible, allowing real-time monitoring on a continuous manufacturing line. In this study, several continuously freeze-dried samples were prepared using formulations and process settings that lead deliberately to specific defects faced in freeze-drying as well as defect-free samples. Two approaches (i.e. patch-based approach and multi-label classification) capable of handling high-resolution images based on Convolutional Neural Networks were developed and compared to select the optimal one. Additional visualization techniques were used to enhance model understanding further. The best approach achieved perfect precision and recall on critical defects, with a prediction time of less than 50 ms to make a decision on the acceptance or rejection of vials generated., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier B.V. All rights reserved.)

This study used Raman and near-infrared (NIR) spectroscopy to monitor small real-time changes in powder blends and tablets in low-dose pharmaceutical formulations. The research aims to enhance process analytical technology (PAT) in pharmaceutical manufacturing, ensuring high-quality and uniform products with applications to produce drugs with narrow therapeutic indices (NTI). The study utilizes Raman and NIR spatially resolved spectroscopy (SRS) techniques to monitor a moderate cohesive material's active pharmaceutical ingredient (API) concentrations during manufacturing. The sampling locations were a bin blender for the batch blending procedure where the powder heterogeneity plays a significant role in product homogeneity, a feed frame of a tablet press where powder blend dynamics is critical to final product quality, and the outlet port of the tablet press where tablets immediately after ejection can be monitored in real-time. The study used semifine acetaminophen (APAP) as the API. Results indicated that Raman and NIR SRS could detect small API concentration changes as low as 0.50 %w/w, demonstrating their sensitivity and utility in real-time monitoring. The findings support the feasibility of these techniques in ensuring tight process control and highlight the performance of reducing waste and optimizing manufacturing processes in line with quality by design principles. The results highlight the importance of residence time distribution (RTD) in understanding the flow of the materials and powder behavior within the tablet press feed frame. RTD analyses showed that both Raman and NIR SRS techniques could effectively track concentration changes and ensure uniformity in the powder blends and tablets with signal-to-noise ratios higher than 3, demonstrating the sensitivity of the methods to small API changes. The %RSD during a steady state of 250 s (corresponding to 1.04 kg of material at 15 kg/h) for the step changes presented values of 6.74 % at 0.50 %w/w, 5.39 % at 1.00 %w/w, and 2.99 % at 1.50 %w/w for Raman predictions in powder blends within the feed frame and 15.46 % at 0.50 %w/w, 9.64 % at 1.00 %w/w, and 5.68 % at 1.50 %w/w for NIR SRS predictions of tablets ejected at the outlet port of the tablet press. In conclusion, this research demonstrates the potential of advanced spectroscopic techniques and data analysis in pharmaceutical manufacturing. By enabling precise real-time monitoring and control, these techniques contribute to higher-quality drug products, particularly NTI drugs, aligning with modern regulatory expectations and advancing pharmaceutical production technology., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Poly(DL-lactide-co-glycolide) (PLGA) and N-methyl-2-pyrrolidone (NMP)-based in situ forming implants are liquid formulations that solidify through phase separation following injection into the body. Drug is dissolved or suspended in the final formulation liquid prior to injection. Depending on the polymers used, the depots formed can deliver drug over different periods of time. Accordingly, it is important to understand the impact of PLGA properties on implant drug release. However, currently available publications only investigate such impacts based on a single drug, which is insufficient to determine the potential interplay between drug and PLGA properties affecting drug release, or to draw any solid conclusions concerning the general impact of PLGA on drug release. The current work explores in situ forming implants with different active pharmaceutical ingredients (APIs) to determine whether any interplay between the APIs and the polymer attributes might affect drug release. In particular, the drug state (solution or suspension form) may impact polymer interaction and drug release. Naproxen and meloxicam were chosen as model drugs and were loaded into in situ forming implants. The final implants of naproxen and meloxicam were solutions and suspensions, respectively. The impact of PLGA properties (slight changes in molecular weight (MW), slight/major changes in lactic/glycolic acid (L/G) ratio, as well as changes in polymer blockiness in end-cap (acid vs ester)) on drug release was investigated. The slight changes in PLGA MW (18-31 KDa), L/G ratio (75/15-85/15) and blockiness had similar impacts on the release of naproxen and meloxicam from the formulations. These impacts were consistent with a previous report on risperidone implants. However, the impact of end-cap and significant change in the L/G ratio (from 75/15-85/15 to 50/50) was determined to be drug dependent. For meloxicam and for risperidone (previous report), the ester end-cap (compared to the acid end-cap) and much higher L/G ratio (75/15-85/15 versus 50/50) resulted in significantly longer overall drug release durations. In contrast, the naproxen implants had shorter release durations when prepared with the ester end-caped polymer (compared to acid end-cap), and when prepared with significantly higher L/G ratio polymers (75/15-85/15 versus 50/50). In addition, using the same PLGA polymer, implants loading different APIs demonstrated different release durations. This work highlights the complexity of PLGA attributes in determining the performance of implant drug formulations and the critical role of the interplay with the API properties. This study provides valuable knowledge for the future development of in situ forming implant drug products., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Over the next decade, Precision Medicine (PM) is poised to become the standard of care in pharmaceutical therapy, necessitating a fundamental transformation in the design and development of innovative custom-made drug products. To date, a comprehensive review linking PM with practical personalized drug formulations is missing. This review attempts to provide an overview of state-of-the-art formulation approaches capable of translating PM evaluation and resulting recommendations (clinical research) into tailored drug products (non-clinical research) for real-world patients. Comprehensive literature searches in four scientific databases (Scopus, SciFinder, Web of Science, and PubMed) were performed. Current approaches to point-of-care PM formulations and needs-based locally distributed manufacturing presently under research & development (R&D) as alternatives to conventional large-scale manufacturing of one-size-fits-all drug products are discussed. The following methods were identified as the most promising PM formulation strategies: tablet splitting, liquid dispensing, compounding pharmacies, additive manufacturing, drug impregnation, drug extrusion, and orodispersible films (ODFs). The challenges and opportunities of current state-of-the-art formulation technologies that can enable making PM routinely accessible in practice settings will be discussed. Additionally, light will be shed on point-of-use manufacturing (Pharmacy on Demand) as an uncharted territory for PM and its pathway towards practical implementation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Rational drug development would be impossible without selecting the appropriate formulation route. However, pharmaceutical scientists often rely on limited personal experiences to perform trial-and-error tests on diverse formulation strategies. Such an inefficient screening manner not only wastes research investments but also threatens the safety of clinical volunteers and patients. A design-oriented paradigm for formulation strategy determination is urgently needed to initiate rational drug development. Herein, we introduce FormulationDT, the first data-driven and knowledge-guided artificial intelligence (AI) platform for rational formulation strategy design. Learning from approved drug formulations, FormulationDT devised a comprehensive formulation strategy design system containing 12 decisions for both oral and injectable administration. Utilizing PU-Decide, our specialized partially supervised learning framework designed for positive-unlabeled (PU) scenarios, FormulationDT developed precise and interpretable classification models for each decision, achieving area under the receiver operating characteristic curve (ROC&#95;AUC) scores ranging from 0.78 to 0.98, with an average above 0.90. Incorporating extensive domain knowledge, FormulationDT is now accessible through a user-friendly web platform (http://formulationdt.computpharm.org/). Moreover, FormulationDT demonstrates its value by showcasing its application in proteolysis targeting chimeras (PROTACs) and recent drug approvals. Overall, this study created the first approved drug formulation dataset and tailored the PU-Decide framework to develop a high-performance, interpretable, and user-friendly AI formulation strategy design platform, which holds promise for driving risk reduction and efficiency gains across the life cycle of drug discovery and development., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Atomization-based techniques are widely used in pharmaceutical industry for production of fine drug particles due to their versatility and adaptability. Key performance measure of such techniques is their ability to provide control over critical quality attributes (CQAs) of produced drug particles. CQAs of drug particles produced via atomization critically depend on fluid dynamics of sprays; resulting mixing, heat and mass transfer; distribution of supersaturation and subsequent nucleation and growth of particles. It is essential to develop and use computational fluid dynamics (CFD) models for adequate understanding of multi-scale transport processes ranging from molecular scale mixing and particle scale processes, and from atomizer nozzle to overall spray chamber scale establishing relationships between CQAs and design and operating parameters of spray nozzle and chamber. In this work, we critically review past and current research efforts on CFD modelling of pharmaceutical atomization-based processes with an objective to provide clear assessment of the state of the art and to provide recommendations. An overview of the key atomization-based methods for producing drug particles with desired CQAs is presented. Key underlying physical processes and relevant concepts are then outlined. This discussion is related to the demands on CFD models; and state of the art is then discussed with respect to the process needs. Recommendations are provided towards higher fidelity and more efficient models of atomized multiphase flow dynamics and turbulence, drying modelling for the produced particles, and validation approaches. We conclude by highlighting a perceived need for numerical atomization studies with a pharmaceutical context; then, we deliver an outlook on current promising active control and machine learning strategies to augment the shift towards quality-by-design approaches in pharmaceutical manufacturing., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved.)

The pharmaceutical industry has expressed a lot of interest in site specific drug delivery & oral controlled release to increase treatment efficiency. The idea of a unique drug delivery system was developed to address several concerns with the physicochemical characteristics of drug molecules and the associated formulations. The use of gastro retentive systems for drug delivery, which focus on site-specific drug release for either systemic or local effects in the stomach, is one of these cutting-edge strategies for lengthening gastric residency time. This approach is especially useful for drugs that have a small window of upper gastro intestinal tract absorption. This review has discussed various gastro-retentive techniques, including floating & non-floating systems. With a focus on the numerous gastro retentive approaches that have lately emerged as the most efficient methods for site specific oral controlled release drug administration, the aim of this study on gastro retentive drug delivery systems was to synthesise the most current findings. We have highlighted the major reasons affecting gastric retention so that you may comprehend the many physiological challenges involved. Next, we discussed the different gastro retentive strategies that have been developed and improved to date, including floating, high density, mucoadhesive, unfoldable, expandable, super porous hydrogel, & magnetic systems. The benefits of gastro retentive medication administration techniques were then thoroughly discussed., Competing Interests: Declarations. Conflict of Interest: The authors declare that they have no conflict of interest., (© 2025. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

This study examines the influence of crospovidone (CP) manufacturer variability on the dissolution profiles of hydrochlorothiazide (HCTZ) tablets. Four CP batches from different manufacturers were characterized using pharmacopeial and physicochemical tests, including infrared absorption, loss on drying, and scanning electron microscopy (SEM). Significant differences were observed in the particle size distribution, wetting time, and water absorption capacities of the CP batches. Tablets were formulated using both direct compression and wet granulation methods. For the latter, the superdisintegrant was either added to the binder solution or incorporated intra- or extra-granularly. Disintegration and dissolution tests revealed that both CP concentration and the method of incorporation significantly affected tablet performance. Poly Kovidone and Max-Povidon exhibited superior performance at lower concentrations, while differences between brands became less pronounced at higher concentrations. The extra-granular method notably enhanced drug release profiles. Statistical analyses, including f 2 similarity factors and MANOVA with Principal Component Analysis (PCA), highlighted significant differences in dissolution behavior among the formulations. These findings emphasize the importance of controlling excipient variability to ensure consistent product performance. The study concludes that a 2% CP concentration is optimal for mitigating source variability and that the extra-granular addition of CP in wet granulation is recommended for enhancing its functional properties., Competing Interests: Declarations. Conflict of Interest: The authors declare that they have no competing interests., (© 2025. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

In vitro methods for quality and equivalence assessment of semi-solid products applied to the skin have increasingly garnered attention because in vivo bioequivalence studies is high cost, complexity, and time-consuming. Regulatory authorities established draft guidelines that outline a modular framework demanding qualitative, quantitative, microstructure and product performance equivalence to support generic products. In line with these guidelines, our study aimed to evaluate the relationship between microstructure and performance attributes in both originator and generic semi-solid products applied to the skin. In this context, reference and three generics of ketoprofen gel were selected as models for semi-solid formulations. Microstructure of all products was assessed regarding pH, specific gravity, drying rate, formulation rheology and potential drug polymorphism. Additionally, performance attributes of products were evaluated using in vitro release testing and in vitro permeation testing. Polymorphism and drying rate data showed no significant difference in microstructure of ketoprofen gels. All tested products exhibited pseudo-plastic flow behavior with thixotropic characteristic. However, differences in pH, specific gravity and viscosity values at low shear stress were observed between reference product and generic products, according to EMA guidance. Although IVRT outcomes did not entirely align with Q3 attributes, IVRT results for reference product versus Generic Product-I and Generic Product-II met the acceptance limits according to FDA guidance, which differs from EMA's assessment. Furthermore, in vitro release rate results were consistent with IVPT data. Consequently, it can be concluded that microstructure of semi-solid products applied to the skin may not consistently correlate with performance attributes due to various alternations influenced by manufacturing process parameters and/or formulation components., Competing Interests: Declarations. Conflict of Interest: There is no conflict of interest with any commercial or other associations in this study., (© 2025. The Author(s).)

Agricultural waste, such as rice straw, has become increasingly valuable as biocomposites in various industries. For cosmetic and pharmaceutical sectors, these biocomposites have improved active substance incorporation and waste reduction, which is pivotal for mitigating environmental impact. This study reports the encapsulation of a protein derivative derived from rice straw within a nanoemulsion for skin care applications, emphasizing stability and efficacy. Protein hydrolysates were produced by extracting proteins in an alkaline medium, followed by precipitation at the isoelectric point. The hydrolysates were enzymatically treated with Alcalase® at 80 °C and pH 10 for 45 min to generate antioxidant-rich formulations. Utilizing Hydrophilic-Lipophilic Deviation (HLD) theory, oil-in-water (O/W) emulsions were formulated by adjusting variables to achieve an HLD near zero. Sunflower oil and surfactants were combined, stirred at 70 °C, and homogenized using a rotor-stator. The final formulation's stability and permeability were evaluated through fluorescence microscopy, particle size analysis, zeta potential measurements, and accelerated stability assays. Nanoemulsion ENE37 showed high stability with 47.25 nm size, PDI 0.21, and excellent dispersion, maintaining integrity without phase separation. Hydrolyzed protein into ENE37 (NE37-HP) improved stability, increasing zeta potential and preventing aggregation while maintaining structure without phase inversion. NE37-HP exhibited shear-thinning behavior and good diffusion capacity, achieving 20.14 μg/cm 2 .h. The HLD theory and ternary diagrams are valuable methodological tools for formulating stable nanoscale emulsions. Additionally, this dosage form, containing protein hydrolysates derived from rice straw, demonstrated potential for adequate dermal absorption in humans., Competing Interests: Declarations. Ethics Approval and Consent to Participate: This article does not contain any studies involving animals performed by any of the authors. This article does not contain any studies involving human participants performed by any of the authors. Consent for Publication: Not applicable. Competing Interests: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article., (© 2025. The Author(s).)

Lipid-based formulations are essential for enhancing drug solubility and bioavailability, yet selecting optimal lipid excipients for specific drugs remains challenging. This study introduces Sol&#95;ME, a machine learning-based model designed to predict drug solubility in lipidic environments, thereby streamlining the formulation process. The Sol&#95;ME model uses PubChem® fingerprints, focusing on solubility correlations with lipid excipients, minimizing reliance on traditional parameters like LogP and molecular weight. The model was trained on a dataset of 1,379 drug-solvent entries and applied to the formulation of Apalutamide, a BCS Class II drug. Experimental validation was performed with 35 drug-solvent combinations to assess the accuracy of predicted solubilities. Sol&#95;ME achieved a high predictive accuracy with a correlation coefficient of 0.998. The model successfully identified Cinnamon oil as the optimal excipient for Apalutamide, further refining the formulation with Vanillin. This reduced formulation volume by 75%, enabling the development of a single-unit 240 mg soft gelatin capsule. Experimental validation showed 80% alignment between predicted and actual solubilities. The Sol&#95;ME model demonstrates significant potential to optimize lipid-based drug formulation, offering a data-driven approach that enhances efficiency. The success of Apalutamide formulation highlights its practical utility. Future work will expand the dataset and extend the model to solid lipid systems, broadening its application in drug delivery technologies., Competing Interests: Declarations. Ethics Approval and Consent to Participate: Not Applicable. Consent for Publication: All authors are agreed to publish the manuscript. Conflicts of Interest: There is no conflict of interest or objection from the side of the authors., (© 2025. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Amorphous solid dispersions (ASDs) are a prevalent method for increasing the bioavailability and apparent solubility of poorly soluble drugs. Consequently, extensive research, encompassing both experimental and computational approaches, has been dedicated to developing methods for assessing the key factors influencing their stability, notably drug-polymer interactions. A common computational approach to rank the compatibility of a drug with a set of solvents or polymers is to compare thermodynamic observables, such as solvation free energies at infinite dilution. However, the impact of the molecular weight of the polymer excipient on these interactions remains underexplored. This study delves into this impact through atomistic simulations of Indomethacin in PVP(-VA) and HPMC, and through simulations using a coarse-grained model, emphasizing its critical importance. First, we demonstrate that the molecular weight of the polymer plays a pivotal role in determining the solvation free energy of the drug, at times exerting a more significant influence than the specific chemical identity of the polymer. Additionally, our simulations suggest that higher molecular weight polymers lead to lower solvation free energies and, thus, suggest better compatibility with the drug. Yet, the lower free energy of solvation of the drug in longer polymers does not translate into a higher solubility. This work highlights the subtle role polymer molecular weight plays when measuring thermodynamic observables in amorphous solid dispersions, a role which must be considered when optimizing pharmaceutical formulations.

Lyophilization remains a key method for preserving sensitive biopharmaceuticals such as monoclonal antibodies. Traditionally, stabilization mechanisms have been explained by vitrification, which minimizes molecular mobility in the lyophilized cake, and water replacement, which restores molecular interactions disrupted by water removal. This study proposes a novel design strategy that combines water activity and glass-transition temperature as the main indicators to predict long-term stability in lyophilized formulations. The water activity, calculated as the product of water activity coefficient and (residual) water content, serves as a mutual indicator of molecular interactions and influence of residual water content in the lyophilizate. By predicting beneficial excipient combinations through activity coefficient calculations using the perturbed-chain statistical association fluid theory model and calculating T g using the Gordon-Taylor equation, the study identifies favorable excipient systems, such as sucrose/ectoine mixtures, providing formulation windows that offer broad stability ranges. The approach was validated with stability studies, confirming that formulations within a water activity range of 0.025-0.25 exhibit high (long-term) stability. This work advances formulation development by integrating water-excipient interactions and residual moisture content into a predictive model, moving beyond traditional empirical methods and offering a robust pathway to the design of stable biopharmaceutical formulations. This makes it possible to achieve high/favorable water activities despite low residual moisture (thus, high glass-transition temperatures) with plausible excipient concentrations and combinations.

A new 3.2 mm 1 H- 19 F-X magic angle spinning dynamic nuclear polarization NMR (MAS DNP-NMR) probe was developed with a unique coil design with separate radiofrequency channels for 1 H excitation and 13 C or 19 F detection to enable acquisition of 1 H- 19 F cross-polarization (CP) MAS experiments, direct-detected 19 F spectra with proton decoupling, and acquisition on 13 C with simultaneous double decoupling on the 1 H and 19F channels as well as 1 H- 19 F- 13 C double-CP experiments under low temperature MAS DNP conditions. We use these sequences to study AZD2811, which is an active pharmaceutical ingredient (API), in its pure dry state as well as in its corresponding drug delivery formulation consisting of drug-loaded polymeric nanoparticles (PNPs). Included in this study are also small interfering RNAs (siRNAs) for therapeutic targeting of peptidyl-prolyl cis-trans isomerase B (Ppib) mRNA. We demonstrate that 1 H- 19 F CP MAS experiments performed on the new HFX probe represent a notable advantage over usually acquired direct-detected 19 F experiments. The indirect 19 F DNP enhancement ε on/off ( 19 F) = 26 was obtained via 1 H- 19 F CP for the pure API impregnated with DNP solution, with an overall 30-fold sensitivity gain compared to the direct-detected 19 F experiment under similar conditions. DNP enhancement value of ε on/off ( 19 F) = 42 was obtained via 1 H- 19 F CP for the polymeric nanoparticle suspension and ε on/off ( 19 F) ≈ 150 were obtained for two different siRNAs in frozen DNP solution., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

(20 S)-Ginsenoside Rh2 is a natural saponin derived from Panax ginseng Meyer (P. ginseng), which showed significantly potent anticancer properties. However, its low water solubility and bioavailability strongly restrict its pharmaceutical applications. The aim of current research is to develop a modified (20 S)-Ginsenoside Rh2 formulation with high solubility, dissolution rate and bioavailability by combined computational and experimental methodology. The "PharmSD" model was employed to predict the optimal polymer for (20 S)-Ginsenoside Rh2 solid dispersion formulations. The solubility of (20 S)-Ginsenoside Rh2 in various polymers was assessed, and the optimal ternary solid dispersion was evaluated across different dissolution mediums. Characterization techniques included the Powder X-ray diffraction (PXRD) and Fourier transform infrared spectroscopy (FTIR). Molecular dynamics simulations were employed to elucidate the formation mechanism of the solid dispersion and the interactions among active pharmaceutical ingredient (API) and excipient molecules. Cell and animal experiments were conducted to evaluate the in vivo performance of the modified formulation. The "PharmSD" solid dispersion model identified Gelucire 44/14 as the most effective polymer for enhancing the dissolution rate of Rh2. Subsequent experiment also confirmed that Gelucire 44/14 outperformed the other selected polymers. Moreover, the addition of the third component, sodium dodecyl sulfate (SDS), in the ternary solid dispersion formulation significantly amplified dissolution rates than the binary systems. Characterization experiments revealed that the API existed in an amorphous state and interacted via hydrogen bonding with SDS and Gelucire. Moreover, molecular modeling results provided additional evidence of hydrogen bonding interactions between the API and excipient molecules within the optimal ternary solid dispersion. Cell experiments demonstrated efflux ratio (EfR) of Rh2 ternary solid dispersion was lower than that of pure Rh2. In vivo experiments revealed that the modified formulation substantially improved the absorption of Rh2 in rats. Our research successfully developed an optimal ternary solid dispersion for Rh2 with high solubility, dissolution rate and bioavailability by integrated computational and experimental tools. The combination of Artificial Intelligence (AI) technology and molecular dynamics simulation is a wise way to support the future formulation development., Competing Interests: Declarations. Ethics approval and consent to participate: No ethical approval is required for this study. Consent to publish: All the authors read and approved the final version of the manuscript. Competing interests: The authors report no conflicts of interest., (© 2024. Controlled Release Society.)

Poloxamer 338 is used as versatile thermo-responsive gelling agent in topical and sub-cutaneous applications. Due to application specific needs a gel point below body or even below room temperature is required. The influence of inorganic salts and active pharmaceutical ingredients (APIs) on the gel point was investigated using oscillatory rheology to identify the driving forces and predictors for gel point alteration. While most inorganic salts decreased the gel point, API salts exhibited an increase. Consistent with previous findings, the extent of gel point alteration caused by inorganic salts could be empirically described by the Hofmeister series, primarily influenced by the anion. Notably, this study revealed a concentration-dependent increase in the gel point in the presence of API salts. Moreover, this increase could be accurately predicted in a linear manner by considering the respective logP value. By utilizing the proposed prediction model, the effect of API addition on the gel point can be estimated, facilitating formulation development to achieve the desired gelling behavior for specific applications., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: All authors are employees of BASF SE, 67,056 Ludwigshafen am Rhein, Germany., (Copyright © 2025. Published by Elsevier B.V.)

Objective: The present study aims to develop and evaluate the voriconazole-loaded thermoresponsive hydrogel using in silico tools., Methods: Poloxamer 407 and PEG 400 were selected as the components from in silico studies for thermoresponsive hydrogel of voriconazole. The cohesive energy density (CED) and solubility parameters (SP) were calculated using Biovia Material Studio 2022 software to predict the polymer-polymer miscibility and drug-polymer miscibility. Different evaluation techniques used to select the optimized formulation. The in vitro antimicrobial activity against Candida albicans was determined for the optimized formulation to illustrate the efficacy of the developed formulation., Results: Hydrogel containing 15% poloxamer exhibited gelation time of 92.67 ± 3.51 s, and gelation temperature of 36.67 °C with good spreadability of 13.00 ± 0.02 cm 2 . CED values for poloxamer 407, PEG 400, and Voriconazole individually were found to be 3.23 × 10 -8 , 3.21 × 10 -8 , 4.84 × 10 -8 , respectively, whereas in the combination of poloxamer 407 and PEG 400 was found to 3.85 × 10 -8 and in ratio 9:1 was found to be 3.81 × 10 -8 indicated the best miscibility between poloxamer 407 and PEG 400 in 9:1 ratio. Based on solvation-free energy of voriconazole (-48.343 kJ/mol) ethanol was selected as the solvent system. Optimized formulation showed the sustained release over the 36 h and good antimicrobial effect., Conclusion: A thermoresponsive hydrogel of voriconazole was developed using Biovia Material Studio 2022, integrating computational predictions and molecular dynamics simulations to streamline polymer and solvent selection. This approach minimized trial-and-error experiments, enabling efficient formulation while enhancing understanding of polymer-polymer and drug-polymer interactions.

Many attempts have been made to integrate medicinal chemistry knowledge into therapeutic decision-making in pharmacy programs across North America. Examples include the use of Structure-Based Therapeutic Evaluations, alignment of medicinal chemistry content with courses in pharmacology, pharmaceutics and pharmacotherapeutics, and team-based or problem-based learning methods. The majority of these approaches indicate that students have greater confidence or comfort with medicinal chemistry, but there remain few cases where an improvement in performance has been measured. This is especially challenging for assessing a student's ability to implement medicinal chemistry learning in pharmacotherapeutic decision-making. Building upon our national special interest group's recent environmental scan of medicinal chemistry instruction in Canadian Pharmacy programs, we are investigating strategies for integration of medicinal chemistry learning in therapeutic decision-making. This commentary will discuss methods and evidence to support medicinal chemistry integration, relevant assessment strategies, and potential paths forward., Competing Interests: Declaration of competing interest The authors listed above have no conflict of interest to declare and no affiliations with or involvement in any organization or entity with any financial interest in this submission., (Copyright © 2024. Published by Elsevier Inc.)

Albendazole, an anthelmintic recognized by the World Health Organization as an essential medicine, is known to have limitations in solubility and bioavailability. To improve these properties, binary and ternary multicomponent systems were designed employing different combinations of albendazole desmotropes with maltodextrin and aspartic acid. The impact of these systems in solution was evaluated through phase solubility analysis. Moreover, solid systems were produced using the kneading method and evaluated with a combination of techniques, including dissolution tests, Fourier-Transform infrared spectroscopy, X-ray powder diffraction, and scanning electron microscopy. These studies demonstrated that multicomponent systems had higher solubility than free desmotropes, with the system formulated using solid form II of albendazole exhibiting the most significant improvement. Additionally, the dissolution percentage of each solid system in simulated gastric fluid was significantly increased. It can therefore be concluded that these innovative systems offer promising alternatives for improving the oral bioavailability of albendazole, generating significant interest in the pharmaceutical field., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)