Search

The amorphization and crystallization of citric acid in the presence of a variety of polymers were investigated. Polymers were chosen for their different physicochemical features, including hygroscopicity, glass transition temperature (Tg), and functional groups capable of forming intermolecular non-covalent interactions with citric acid. Citric acid solutions with varying amounts of pectin (PEC), guar gum (GG), κ-carrageenan (KG), gelatin (GEL), (hydroxypropyl)methylcellulose (HPMC), and carboxymethylcellulose sodium (CMC-Na) were lyophilized. Dispersions were stored for up to 6 months in controlled temperature and relative humidity environments and periodically monitored using powder X-ray diffraction, differential scanning calorimetry, and Fourier transform infrared spectroscopy. Moisture sorption isotherms and moisture contents were determined. Amorphous solid dispersions of citric acid were successfully formed in the presence of ≥20% w/w CMC-Na and PEC or ≥30% w/w of the other polymers except KG which required a minimum of 40% polymer. All samples remained amorphous even in their rubbery state at 0% RH (25 °C and 40 °C), but increasing the RH to 32% RH resulted in citric acid crystallization in the KG dispersions, and further increasing to 54% RH resulted in crystallization in all samples. Polymer effectiveness for inhibiting citric acid crystallization was CMC-Na > PEC ≥ GEL > HPMC > GG > KG. To create and maintain amorphous citric acid, polymer traits in order of effectiveness were as follows: greater propensity for intermolecular non-covalent interactions (both ionic and hydrogen bonding) with the citric acid, carbonyl groups, higher Tg, and then lower hygroscopicity. [ABSTRACT FROM AUTHOR]

Pretomanid (PTM), an oral antibiotic used in the treatment of adults with pulmonary extensively drug-resistant, nonresponsive multidrug-resistant tuberculosis (MDR-TB). It is a poor glass former, that shows high recrystallization tendency from the amorphous and supersaturated state, resulting in low aqueous solubility and suboptimal absorption through the gastrointestinal tract. The present investigation aimed to develop high drug loaded ternary amorphous solid dispersions (ASDs) of PTM with improved stability and enhanced biopharmaceutical performance by utilizing a combination of polymers. The polymers were comprehensively screened based on drug-polymer miscibility and saturation solubility analysis. A combination of Hydroxypropyl Methylcellulose Acetate Succinate (HPMCAS-HF) and Polyvinylpyrrolidone K-30 (PVP K-30) showed synergism in drug-polymer miscibility as evidenced through pronounced depression in the melting endotherm of PTM. The Powder X-ray Diffraction (P-XRD) diffractograms of 30% w/w PTM loaded ternary ASDs displayed the halo pattern, contrary to the binary ASDs. Drug-polymer interactions (hydrophobic forces) involved between PTM and polymers were detected through Fourier Transform Infrared Spectroscopy (FT-IR) and Nuclear Magnetic Resonance Spectroscopy (13C-NMR) which contributed to the synergistic enhancement in solubility and dissolution of ternary ASDs with sustained release over 12 h. Ternary ASDs demonstrated better in-vivo performance compared to the binary ASDs, showing a 4.63-fold increase in maximum plasma concentration. All ASDs remained stable and resisted phase separation during short-term stability studies for 3 months at ambient conditions. It was concluded that the hydrophobic and hydrophilic polymeric combination (HPMCAS-HF and PVP K-30, respectively) effectively prevented the crystallization and ensured sustained drug release with improved in-vivo absorption of PTM. [ABSTRACT FROM AUTHOR]

Background: Curcumin and hesperetin are plant polyphenols known for their poor solubility. To address this limitation, we prepared amorphous PVP K30–phosphatidylcholine dispersions via hot-melt extrusion. Methods: This study aimed to evaluate the effects of the amounts of active ingredients and phosphatidylcholine, as well as the process temperature, on the performance of the dispersions. A Box–Behnken design was employed to assess these factors. Solid-state characterization and biopharmaceutical studies were then conducted. X-ray powder diffraction (XRPD) was used to confirm the amorphous nature of the dispersions, while differential scanning calorimetry (DSC) provided insight into the miscibility of the systems. Fourier-transform infrared spectroscopy (FTIR) was employed to assess the intermolecular interactions. The apparent solubility and dissolution profiles of the systems were studied in phosphate buffer at pH 6.8. In vitro permeability across the gastrointestinal tract and blood–brain barrier was evaluated using the parallel artificial membrane permeability assay. Results: The quantities of polyphenols and phospholipids were identified as significant factors influencing the biopharmaceutical performance of the systems. Solid-state analysis confirmed the formation of amorphous dispersions and the development of interactions among components. Notably, a significant improvement in solubility was observed, with formulations exhibiting distinct release patterns for the active compounds. Furthermore, the in vitro permeability through the gastrointestinal tract and blood–brain barrier was enhanced. Conclusions: The findings suggest that amorphous PVP K30–phosphatidylcholine dispersions have the potential to improve the biopharmaceutical properties of curcumin and hesperetin. [ABSTRACT FROM AUTHOR]

Amorphous solid dispersion (ASD) technology is often used as a promising strategy to improve the solubility of active pharmaceutical ingredients (APIs). ASDs allow APIs to be dispersed at the molecular level in a polymer carrier, destroying the crystalline structure of the APIs and, thanks to the polymer, providing long-term supersaturation in solution. However, stability issues are an obstacle to the development of new medications with ASD. In addition to the molecular mobility at elevated temperatures leading to the crystallization of APIs, moisture affects the physical stability of ASD, leading to fractional separation and recrystallization. N-butyl-N-methyl-1-phenylpyrrolo[1,2-a]pyrazine-3-carboxamide (GML-3) is an original API with both anxiolytic and antidepressant activity, but its insolubility in water can negatively affect (influence) bioavailability. Our study aims to create ASD GML-3 with moisture-resistant polymers (Soluplus®, HPC) and assess the stability of the amorphous state of ASD after storage in high humidity conditions. As a result, HPC KlucelTM FX was revealed to be more stable than the brand, providing a high level of API release into the purified water environment and stability after 21 days (3 weeks) of storage in high humidity conditions. [ABSTRACT FROM AUTHOR]

Amorphous solid dispersions (ASDs) represent a promising strategy for enhancing the solubility of poorly soluble drugs. However, the mechanisms underlying the physical stability of ASDs remain insufficiently understood. This study aims to investigate these mechanisms and propose quantitative thresholds to predict the maximum stable drug loading using molecular dynamics simulations. Poly(vinylpyrrolidone) (PVP) and poly (vinylpyrrolidone-co-vinyl acetate) (PVPVA64) are selected as polymeric carriers, while naproxen and acetaminophen serve as model drugs, resulting in the formulation of 18 distinct ASDs across four types for comparison with experimental results. Our findings indicate that the molecular mobility of active pharmaceutical ingredients (APIs) is the primary determinant of solid dispersion stability. High polymer concentrations limit drug molecular mobility through spatial structural constraints and ASD viscosity. As drug loading increases, the polymer concentration reaches a critical threshold (C*), beyond which drug-rich regions form, leading to potential aggregation, rearrangement, and recrystallization of drug molecules into more energetically stable forms. Notably, both the interaction energy and diffusion coefficient show sharp fluctuations at the maximum stable drug loading, which can serve as predictive indicators for ASD stability. Additionally, a search strategy is used to identify potential pre-crystalline sites. By integrating kinetic, thermodynamic, and pre-crystalline analyses through molecular dynamics simulations, this study provides a foundation for more accurate predictions of ASD stability, significantly aiding future formulation development. [ABSTRACT FROM AUTHOR]

Developing orally administered pediatric formulations presents significant challenges due to the unique characteristics of pediatric patients. Terbinafine hydrochloride (TER), a powerful antifungal agent, is effective against various fungal infections, including Tinea capitis, which is common in children. However, its low aqueous solubility necessitates innovative pharmaceutical strategies to enhance its effectiveness. This study describes a rational approach to selecting suitable carriers, approved for use in children, to increase the apparent solubility of TER and to guide the development of amorphous solid dispersions containing this drug. Assessments of solubility parameters, equilibrium solubility measurements, and calculations of pediatric dose numbers guided formulation development using theoretical and experimental methodologies. Carriers like Plasdone S-360 ULTRA®, HPMCAS L, and Soluplus® demonstrated favorable solubility parameter values with TER, indicating potential for drug solubilization. The solubility of TER was strongly dependent on pH. In buffer pH 6.5 containing 10% (w/v) of Soluplus®, TER presented the highest solubility value. The solid-state characterization techniques employed to assess the precipitate formed after equilibrium solubility studies during preformulation demonstrated that there were no phase transitions and no significant interactions between the drug and the evaluated carriers. Furthermore, the results demonstrate that Soluplus® achieved the lowest dose number (0.23) for pediatric patients over 6 years old. So, it was selected for preparing the amorphous solid dispersion via spray drying, which significantly enhanced the apparent solubility of TER while maintaining prolonged supersaturation, offering a promising alternative for developing solid formulations of this drug, particularly for pediatric patients, as it aims to improve oral bioavailability. [ABSTRACT FROM AUTHOR]

Plant extracts demonstrate significant potential as a rich source of active pharmaceutical ingredients, exhibiting diverse biological activities and minimal toxicity. However, the low aqueous solubility of extracts and their gastrointestinal permeability, as well as their poor oral bioavailability, limit clinical advancements due to drug delivery problems. An amorphous solid dispersion (ASD) delivers drugs by changing an active pharmaceutical ingredient (API) into an amorphous state to increase the solubility and availability of the API to the body. This research aimed to analyze and summarize the successful advancements of ASD systems derived from plant extracts, emphasizing characterization and the effects on dissolution and pharmacological activity. The results show that ASD systems improve phytoconstituent dissolution, bioavailability, and stability, in addition to reducing dose and toxicity. This research demonstrates the significance of ASD in therapeutic formulations to augment the pharmacological activities and efficacy of medicinal plant extracts. The prospects indicate promising potential for therapeutic applications utilizing ASD systems, alongside medicinal plant extracts for clinical therapy. [ABSTRACT FROM AUTHOR]

Itraconazole (ITZ), a broad-spectrum triazole antifungal agent, exhibits remarkable pharmacodynamic and pharmacokinetic properties. However, the low solubility of ITZ significantly reduces its oral bioavailability. Furthermore, it has been reported that this medication can result in dose-related adverse effects. Therefore, the objective of this study was to enhance the solubility of ITZ through the utilization of various polymers and to manufacture personalized and programmable release ITZ tablets. Five different polymers were selected as water-soluble carriers. Thirty percent w/w ITZ was mixed with seventy percent w/w of the polymers, which were then extruded. A series of physical and chemical characterization studies were conducted, including DSC, PXRD, PLM, and in vitro drug release studies. The results demonstrated that ITZ was dispersed within the polymers, forming ASDs that markedly enhanced its solubility and dissolution rate. Consequently, soluplus® was employed as the polymer for the extrusion of ITZ-loaded filaments, which were subsequently designed and printed. The in vitro drug release studies indicated that the release of ITZ could be regulated by modifying the 3D structure design. Overall, this study found that the combination of HME and 3D printing technologies could represent an optimal approach for the development of personalized and precise drug delivery dosages. [ABSTRACT FROM AUTHOR]

Background/Objectives: This study evaluates the efficacy of twin screw melt granulation (TSMG), and hot-melt extrusion (HME) techniques in enhancing the solubility and dissolution of simvastatin (SIM), a poorly water-soluble drug with low bioavailability. Additionally, the study explores the impact of binary polymer blends on the drug's miscibility, solubility, and in vitro release profile. Methods: SIM was processed with various polymeric combinations at a 30% w/w drug load, and a 1:1 ratio of binary polymer blends, including Soluplus® (SOP), Kollidon® K12 (K12), Kollidon® VA64 (KVA), and Kollicoat® IR (KIR). The solid dispersions were characterized using modulated differential scanning calorimetry (M-DSC), powder X-ray diffraction (PXRD), and Fourier-transform infrared spectroscopy (FTIR). Dissolution studies compared the developed formulations against a marketed product. Results: The SIM-SOP/KIR blend showed the highest solubility (34 µg/mL), achieving an approximately 5.5-fold enhancement over the pure drug. Dissolution studies showed that SIM-SOP/KIR formulations had significantly higher release profiles than the physical mixture (PM) and pure drug (p < 0.01). Additionally, their release was similar to a marketed formulation, with 100% drug release within 30 min. In contrast, the SIM-K12/KIR formulation exhibited strong miscibility, but limited solubility and slower release rates, suggesting that high miscibility does not necessarily correlate with improved solubility. Conclusions: This study demonstrates the effectiveness of TSMG, and HME as effective continuous manufacturing technologies for improving the therapeutic efficacy of poorly water-soluble drugs. It also emphasizes the complexity of polymer–drug interactions and the necessity of carefully selecting compatible polymers to optimize the quality and performance of pharmaceutical formulations. [ABSTRACT FROM AUTHOR]

Background: Active pharmaceutical ingredient (API) content is a critical quality attribute (CQA) of amorphous solid dispersions (ASDs) prepared by spraying a solution of APIs and polymers onto the excipients in fluid bed granulator. This study presents four methods for quantifying API content during ASD preparation. Methods: Raman and three near-infrared (NIR) process analysers were utilized to develop methods for API quantification. Four partial least squares (PLS) models were developed using measurements from three granulation batches, with an additional batch used to evaluate model predictability. Models performance was assessed using metrics such as root mean square error of prediction (RMSEP), root mean square error of cross-validation (RMSECV), residual prediction deviation (RPD), and others. Results: Off-line and at-line NIR models were identified as suitable for process control applications. Additionally, at-line Raman measurements effectively predicted the endpoint of the spraying phase. Conclusions: To the best of authors' knowledge, this is the first study focused on monitoring API content during fluidized bed granulation (FBG) used for ASD preparation. The findings provide novel insights into the application of Raman and NIR process analysers with PLS modelling for monitoring and controlling ASD preparation processes. [ABSTRACT FROM AUTHOR]

Formulation of amorphous solid dispersion (ASD) of any poorly water-soluble drug is among the most promising techniques to increase the dissolution profile of drug and hence its bioavailability. Various literatures give evidences of the role of drug-polymer interactions in the ASD systems, very little information is available about the surface properties of the drug molecule and their ASDs which contributes to a higher dissolution profile. Current work focuses on exploring the surface behavior of a poorly water-soluble drug Riluzole (RLZ) and its ASDs prepared with two highly hydrophilic polymers, polyacrylic acid (PAA), and polyvinylpyrrolidone vinyl acetate (PVP VA). Initial characterization using X-ray diffraction (XRD) revealed about the weight fraction of drug required to prepare a single-phase homogenous system with both the polymers. The saturation solubility and the dissolution studies showed an increase in RLZ solubility as well as the dissolution profile due to the presence of polymers. The role of polymers in changing the surface properties in terms of wettability and polarity were explored using contact angle method and X-ray photon spectroscopy (XPS). Additionally, the neuroprotective efficacy and dose dependent hepatotoxicity were also evaluated in male wistar rats. These studies confirmed the increase in the surface polarity and hence the enhanced ability of ASD formulations to interact with water. The in vivo studies indicated that at the current recommended dose the efficacy as well as toxicity is increased for the ASD formulation. Hence, this formulation can be given at a lower dose to achieve same therapeutic effect with lower toxicity. [ABSTRACT FROM AUTHOR]

Objectives The objective of this research was to enhance the bioavailability of ursolic acid (UA) by preparing multielement amorphous solid dispersion (ASD) systems comprising excipients. Methods The ASDs were prepared via the solvent evaporation method, characterized by a range of techniques, and investigated with respect to permeability of human colorectal adenocarcinoma cell line (Caco-2) cells monolayers and pharmacokinetics, with comparisons made to the physical mixture and the pure drug. Key findings The (UA-choline)-Polyethylcaprolactam—polyvinyl acetate—polyethylene glycol grafted copolymer (Soluplus)-Vitamin E polyethylene glycol succinate (TPGS) ASD demonstrated superior dissolution properties compared to the corresponding binary solid dispersions and ternary solid dispersions (P <.05). The permeability studies of Caco-2 cell monolayers revealed that the ASD exhibited moderate permeability, with an efflux rate that was significantly lower than that of the UA raw material (P <.05). Pharmacokinetic studies in rats demonstrated that the oral bioavailability of the ASD was 19.0 times higher than that of UA (P <.01). Conclusions The research indicated that the multielement ASD could be employed as an efficacious drug delivery system for UA. Furthermore, the Soluplus/TPGS/choline combination represents a promising candidate for the fabrication of ASDs that can load weakly acidic and poorly soluble drugs. [ABSTRACT FROM AUTHOR]

A pioneering approach in the domain of transdermal drug delivery systems (TDDS) is introduced by using microneedles (MNs) fabricated from an amorphous solid dispersion comprising only a model drug and an amphiphilic block copolymer to form a drug nanoformulation upon MN dissolution. To maximize drug loading and ensure consistent release, a minimalist formulation that achieves 40 wt% drug loading, which is a significant improvement over existing methods, is developed. Using scanning electron microscopy, the morphology of MNs is examined across a spectrum of drug loading ratios, demonstrating the consistency in structure and integrity. Mechanical testing confirms the MNs' proficiency in effective skin penetration. A comparative study on the formation of polymeric micelles underscores the innovative concept of a "nano‐in‐micro drug delivery system". The results demonstrate that MNs manufactured from an amorphous solid dispersion of drug and amphiphilic block copolymer with ultra‐high loading enhance the availability and release dynamics of hydrophobic drugs, positioning them as a tool for enhancing TDDS. This study sets a new benchmark in the utilization of polymer‐drug nanoformulations for transdermal applications and underscores the capacity for high drug loading and the creation of adaptable drug delivery mechanisms for the studied amphiphilic block copolymer. [ABSTRACT FROM AUTHOR]

Dasatinib (DAS) is a drug used in the treatment of chronic myeloid and acute lymphoblastic leukemia. While DAS exhibits good intestinal permeability, its poor solubility in aqueous medium limits its bioavailability. To enhance DAS’s release profile, solid dispersions of DAS and polyvinylpyrrolidone (PVP), with a DAS mass fraction of 25 %, were prepared mechanochemically in a planetary ball mill under four different process conditions. These solid dispersions were produced without a solvent, following the principles of green chemistry. The solid dispersions were characterized using differential scanning calorimetry, X-ray powder diffraction, and Fourier transform infrared spectroscopy to determine the thermal properties and phase composition of the solid dispersions, as well as possible interactions between DAS and PVP. Four types of tablets were prepared, containing: original DAS, mechanochemically treated DAS, a physical mixture of DAS and PVP, and a solid dispersion of DAS and PVP prepared under optimised process conditions. Granules of excipients used in the tablet formulations included mannitol, croscarmellose sodium, and polyethylene glycol. The tablets were tested for uniformity of mass and drug content, hardness, and disintegration properties. DAS release profiles were determined through in vitro dissolution testing. The mechanochemical preparation of amorphous solid dispersions was found to modify the release profile of DAS. [ABSTRACT FROM AUTHOR]

Background: Alpha mangostin (AM) has demonstrated significant potential as an anticancer agent, owing to its potent bioactivity. However, its clinical application is limited by poor solubility, which hampers its bioavailability and effectiveness. Amorphous solid dispersion (ASD) presents a promising technique to enhance the solubility and stability of AM. Molecular dynamics simulation offers a rapid, efficient, and precise method to evaluate and optimize ASD formulations before production. Aim of Study: In this study, we conducted molecular dynamics simulations to explore the ASD development of AM with poloxamer and pullulan. Result: Our results revealed that AM–poloxamer complexes exhibit superior interaction characteristics compared to AM–pullulan, with a 1:5 ratio of AM to poloxamer and a cooling rate of 1 °C/ns demonstrating the most favorable outcomes. This combination showed enhanced hydrogen bonding, a more compact molecular structure, and higher stability, making it the optimal choice for ASD formulation. Conclusion: The integration of molecular dynamics simulation into ASD development significantly accelerates the formulation process and provides critical insights into achieving a stable and effective AM dispersion. The AM–poloxamer complex, particularly at a 1:5 ratio with a 1 °C/ns cooling rate, offers the best potential for improving AM solubility and therapeutic efficacy. [ABSTRACT FROM AUTHOR]

Background/Objectives: Drug–polymer interactions and miscibility promote the formation and performance of amorphous solid dispersions (ASDs) of poorly soluble drugs for improved oral bioavailability. The objective of this study was to employ drug–polymer interaction calculations and small-scale experimental characterization to screen polymers for potential ASDs of ritonavir. Methods: Seven polymers across four polymer types were screened as follows: an enteric one (EudragitS100), amphiphilic ones (HPMCAS-L, HPMCAS-H, and their 1:1 combination), hydrophilic ones (PEG-6000, PVP-VA), and a surfactant (Soluplus), including PVP-VA as a positive control, as the commercial ASD employs PVP-VA. Drug–polymer interaction calculations were performed for Hansen solubility parameter, Flory–Huggins parameter, and glass transition temperature. ASDs were prepared via film casting. Experimental characterizations included drug solubility in polymer solutions, polymer inhibition of drug precipitation, polarized light microscopy, differential scanning calorimetry, solubilization capacity, and dissolution studies. Results: HPMCAS-L, HPMCAS L:H, and Soluplus, along with the positive control PVP-VA, were identified as polymers for potential ASDs of ritonavir, with HPMCAS-L and PVP-VA being preferable. HPMCAS-L and the positive control PVP-VA were always viable for both 20% and 40% drug loads across all tests. Films with each of these four polymers showed improved dissolution compared to amorphous ritonavir without polymer. Drug–polymer interaction calculations anticipated the unfavorable small-scale experimental results for PEG-6000 and EudragitS100. Conclusion: Overall, the results contribute towards a resource-sparing approach to identify polymers for ASDs. [ABSTRACT FROM AUTHOR]

Background: During the dissolution of amorphous solid dispersion (ASD) formulations, the drug load (DL) often impacts the release mechanism and the occurrence of loss of release (LoR). The ASD/water interfacial gel layer and its specific phase behavior in connection with DL strongly dictate the release mechanism and LoR of ASDs, as reported in the literature. Thermodynamically driven liquid-liquid phase separation (LLPS) and/or drug crystallization at the interface are the key phase transformations that drive LoR. Methods: In this study, a combination of Perturbed-Chain Statistical Associating Fluid Theory (PC-SAFT) thermodynamic modeling and in silico molecular simulation was applied to investigate the release mechanism and the occurrence LoR of an ASD formulation consisting of ritonavir as the active pharmaceutical ingredient (API) and the polymer, polyvinylpyrrolidone-co-vinyl acetate (PVPVA64). A thermodynamically modeled ternary phase diagram of ritonavir (PVPVA64) and water was applied to predict DL-dependent LLPS in the ASD/water interfacial gel layer. Microscopic Erosion Time Testing (METT) was used to experimentally validate the phase diagram predictions. Additionally, in silico molecular simulation was applied to provide further insights into the phase separation, the release mechanism, and aggregation behavior on a molecular level. Results: Thermodynamic modeling, molecular simulation, and experimental results were consistent and complementary, providing evidence that ASD/water interactions and phase separation are essential factors driving the dissolution behavior and LoR at 40 wt% DL of the investigated ritonavir/PVPVA64 ASD system, consistent with previous studies. Conclusions: This study provides insights into the potential of blending thermodynamic modeling, molecular simulation, and experimental research to comprehensively understand ASD formulations. Such a combined approach can be leveraged as a computational framework to gain insights into the ASD dissolution mechanism, thereby facilitating in silico screening, designing, and optimization of formulations with the benefit of significantly reducing the number of experimental tests. [ABSTRACT FROM AUTHOR]

The study examined the efficacy of additives in preventing the crystallization of functional ingredients during the spray-drying process. Spray-drying of a hydrophobic drug from alcohol in the presence of a hydrophilic carrier-forming agent was utilized as a representative scenario, which frequently leads to the crystallization of the main drug component induced by the drying process. Ibuprofen (IBP) and its four congeners were employed as representatives of readily crystallizable hydrophobic pharmaceutical compounds. Disaccharides were intentionally employed as components of the drug carrier to create conditions conducive to crystallization. Ten materials, including the IBP congeners, were investigated for their anti-crystallization properties. The findings indicated that additives with a hydrophobic moiety similar to that of IBP and a carboxylic acid salt moiety effectively prevented IBP and its congeners from crystallizing when the additive content was ≥0.2 g/g-drug during spray-drying and storage at 30 °C over silica gel. [ABSTRACT FROM AUTHOR]

Lopinavir (LPV) and ritonavir (RTV) are two of the essential antiretroviral active pharmaceutical ingredients (APIs) characterized by poor solubility. Hence, attempts have been made to improve both their solubility and dissolution rate. One of the most effective approaches used for this purpose is to prepare amorphous solid dispersions (ASDs). To our best knowledge, this is the first attempt aimed at developing ASDs via the electrospinning technique in the form of fibers containing LPV and RTV. In particular, the impact of the various polymeric carriers, i.e., Kollidon K30 (PVP), Kollidon VA64 (KVA), and Eudragit® E100 (E100), as well as the drug content as a result of the LPV and RTV amorphization were investigated. The characterization of the electrospun fibers included microscopic, DSC, and XRD analyses, the assessment of their wettability, and equilibrium solubility and dissolution studies. The application of the electrospinning process led to the full amorphization of both the APIs, regardless of the drug content and the type of polymer matrix used. The utilization of E100 as a polymeric carrier for LPV and KVA for RTV, despite the beads-on-string morphology, had a favorable impact on the equilibrium solubility and dissolution rate. The results showed that the electrospinning method can be successfully used to manufacture ASDs with poorly soluble APIs. [ABSTRACT FROM AUTHOR]

The focus of the present work was to develop amorphous solid dispersion (ASD) formulation of aprepitant (APT) using sucrose acetate isobutyrate (SAIB) excipient, evaluate for physicochemical attributes, stability, and bioavailability, and compared with hydroxypropyl methylcellulose (HPMC) based formulation. Various formulations of APT were prepared by solvent evaporation method and characterized for physiochemical and in-vivo performance attributes such as dissolution, drug phase, stability, and bioavailability. X-ray powder diffraction indicated crystalline drug conversion into amorphous phase. Dissolution varied as a function of drug:SAIB:excipient proportion. The dissolution was more than 80% in the optimized formulation (F10) and comparable to HPMC based formulation (F13). Stability of F10 and F13 formulations stored at 25 C/60% and 40°C/75% RH for three months were comparable. Both ASD formulations (F10 and F13) were bioequivalent as indicated by the pharmacokinetic parameters Cmax and AUC0-∞. Cmax and AUC0-∞ of F10 and F13 formulations were 2.52 ± 0.39, and 2.74 ± 0.32 μg/ml, and 26.59 ± 0.39, and 24.79 ± 6.02 μg/ml.h, respectively. Furthermore, the bioavailability of ASD formulation was more than twofold of the formulation containing crystalline phase of the drug. In conclusion, stability and oral bioavailability of SAIB based ASD formulation is comparable to HPMC-based formulation of poorly soluble drugs. [ABSTRACT FROM AUTHOR]