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AbstractThe aim of research is to enhance the solubility of crystalline gefitinib (GF), a poorly water-soluble drug, by developing drug delivery systems using chitosan oligosaccharide (COS) particle engineering. Fabrication utilizes ionic gelation followed by spray drying. The preliminary evaluations such as Uv-Vis, FTIR, DSC followed by advanced techniques like SEM and invitro drug release characteristics was performed along with solubility study. The spray-dried particles measured a mean diameter of 3.18 ± 0.5 microns, %EE as well as load w/w improved from 63.25 ± 2.1% and 37.98 ± 1.5% w/w (COS nanoparticles) to 78.15 ± 2.6% and 45.34 ± 1.6% w/w (engineered microparticles), respectively. The zeta potential and in vitro studies demonstrated 41 ± 3.5 mV and 92 ± 2.1% (w/w) release suggest long-term stability and prolonged release. This novel engineering approach effectively enhances GF solubility and surface characteristics, offering promising potential for improving delivery characteristics. [ABSTRACT FROM AUTHOR]

In this study, Felodipine-loaded nanoparticles were prepared using the nanoprecipitation method, with quince seed mucilage serving as the polymer matrix and Tween 80 utilized as a stabilizing agent. The nanoparticles were thoroughly characterized using a range of analytical techniques, including dynamic light scattering (DLS), zeta potential measurement, Fourier-transform infrared spectroscopy (FTIR), thermal analysis, X-ray diffraction (XRD), and scanning electron microscopy (SEM). The Felodipine nanoparticles displayed an amorphous structure, with formulation FEL 4 achieving the highest entrapment efficiency of 67.68%. This formulation also had an average particle size of 675 ± 2.04 nm and a zeta potential of − 31.7 ± 1.34 mV. Saturation solubility tests revealed a significant enhancement in water solubility for the nanoparticles compared to pure Felodipine. Additionally, in vitro drug release studies demonstrated a sustained release profile over 24 h in phosphate buffer. Acute oral toxicity evaluations confirmed that the Felodipine nanoparticles did not exhibit any signs of toxicity. Overall, this study showed the successful fabrication of quince seed mucilage-based Felodipine-loaded nanoparticles as a promising approach to enhance solubility and achieve sustained drug release, with no evident toxicity. [ABSTRACT FROM AUTHOR]

Oils and lipids help make water-insoluble drugs soluble by dispersing them in an aqueous medium with the help of a surfactant and enabling their absorption across the gut barrier. The emergence of microemulsions (thermodynamically stable), nanoemulsions (kinetically stable), and self-emulsifying drug delivery systems added unique characteristics that make them suitable for prolonged storage and controlled release. In the 1990s, solid-phase lipids were introduced to reduce drug leakage from nanoparticles and prolong drug release. Manipulating the structure of emulsions and solid lipid nanoparticles has enabled multifunctional nanoparticles and the loading of therapeutic macromolecules such as proteins, nucleic acid, vaccines, etc. Phospholipids and surfactants with a well-defined polar head and carbon chain have been used to prepare bilayer vesicles known as liposomes and niosomes, respectively. The increasing knowledge of targeting ligands and external factors to gain control over pharmacokinetics and the ever-increasing number of synthetic lipids are expected to make lipid nanoparticles and vesicular systems a preferred choice for the encapsulation and targeted delivery of therapeutic agents. This review discusses different lipids and oil-based nanoparticulate systems for the delivery of water-insoluble drugs. The salient features of each system are highlighted, and special emphasis is given to studies that compare them. [ABSTRACT FROM AUTHOR]

Background/Objectives: Amorphization of an active pharmaceutical ingredient (API) can improve its dissolution and enhance bioavailability. Avoiding solvents for drug amorphization is beneficial due to environmental issues and potential solvent residues in the final product. Methods: Dry amorphization using a twin-screw extruder is presented in this paper. A blend of mesoporous silica particles and crystalline itraconazole was processed using a pharma-grade laboratory scale twin-screw extruder. The influence of different screw configurations and process parameters was tested. Particle size and shape are compared in scanning electron microscopy (SEM) images. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) are used to determine the residual amount of crystalline itraconazole in the final product. Results: An optimized screw configuration for the process was found which leads to more than 90% amorphous API when processed at room temperature. Full amorphization was reached at 70 °C. The specific mechanic energy (SME) introduced into the material during twin-screw processing is crucial for the dry amorphization. The higher the SME, the lower the residual amount of crystalline API. Two months after processing, however, recrystallization was observed by XRD. Conclusions: Dry processing using a twin-screw extruder is continuous, free of solvents and can be performed at low temperatures. This study proves the concept of twin-screw processing with mesoporous silica for dry amorphization of itraconazole. [ABSTRACT FROM AUTHOR]

Limited solubility is the main cause of the low local availability of anti-candidiasis drug, miconazole nitrate (MN). The study's objective was to develop and characterize microemulsion (ME) based temperature-triggered in situ gel of MN for intravaginal administration to enhance local availability and antifungal activity. The solubility of MN was initially studied in different oils, surfactants, and co-surfactants. Then, pseudo-ternary phase diagrams were constructed to select the best ratio of various components. The ME formulations were characterized by thermodynamic study, droplet size, polydispersity index (PDI), viscosity, and in-vitro antifungal mean inhibition zone (MIZ). Selected MEs were incorporated into different in situ gel bases using a combination of two thermosensitive polymers (poloxamer (PLX) 407 and 188), with 0.6% of hydroxypropyl methylcellulose (HPMC K4M) and gellan gum (GG) as mucoadhesive polymer. ME-based gels (MG) were investigated for gelation temperature, gelation time, viscosity, spreadability, mucoadhesive strength, in vitro release profile, and MIZ test. Furthermore, the optimum MG was assessed for in vivo animal irritation test and FESEM investigation. Tea tree oil, lavender oil, tween 80, and propylene glycol (PG) were chosen for ME preparation for the optimal formulation; formulation ME7 and ME10 were chosen. After incorporation of the selected formulation into a mixture of P407 and P188 (18:2% w/w) with 0.6% mucoadhesive polymer, the resultant MG formulation (MG1) revealed optimum gelation temperature (33 ± 0.01℃) and appropriate viscosity with enhanced sustained release (98%) and retention through sheep vaginal mucosa, MG1 exhibited a better MIZ compared to the 2% MN gel formulation and the marketed MN product, and no rabbit vagina irritation. In conclusion, the miconazole nitrate-loaded MG-based formula sustained the duration of action and better antifungal activity than the marketed miconazole nitrate formulation. [ABSTRACT FROM AUTHOR]

Objectives: The study explores the potential of various deep eutectic solvents (DESs) to serve as drug delivery systems and pharmaceutical excipients. The research focuses on two primary objectives: evaluating the ability of the selected DES systems to enhance the solubility of two poorly water-soluble model drugs (IBU and MFA), and evaluating their physicochemical properties, including density, viscosity, flow behavior, surface tension, thermal stability, and water dilution effects, to determine their suitability for pharmaceutical applications. Methods: A range of DES systems containing pharmaceutically acceptable constituents was explored, encompassing organic acid-based, sugar- and sugar alcohol-based, and hydrophobic systems, as well as menthol (MNT)-based DES systems with common pharmaceutical excipients. MNT-based DESs exhibited the most significant solubility enhancements. Results: IBU solubility reached 379.69 mg/g in MNT: PEG 400 (1:1) and 356.3 mg/g in MNT:oleic acid (1:1), while MFA solubility peaked at 17.07 mg/g in MNT:Miglyol 812®N (1:1). In contrast, solubility in hydrophilic DES systems was significantly lower, with choline chloride: glycerol (1:2) and arginine: glycolic acid (1:8) showing the best results. While demonstrating lower solubility compared to the MNT-based systems, sugar-based DESs exhibited increased tunability via water and glycerol addition both in terms of solubility and physicochemical properties, such as viscosity and surface tension. Conclusions: Our study introduces novel DES systems, expanding the repertoire of pharmaceutically acceptable DES formulations and opening new avenues for the rational design of tailored solvent systems to overcome solubility challenges and enhance drug delivery. [ABSTRACT FROM AUTHOR]

This study focuses on the formulation and evaluation of azilsartan medoxomil solid dispersions utilizing polyvinylpyrrolidone to enhance water solubility and dissolution rates. The research involved two preparation methods: solvent evaporation and kneading techniques. Findings reveal that solid dispersions created through the solvent evaporation technique significantly outperform those made by kneading in terms of solubility improvements. Among the various formulations tested, B3, which utilized a drug-to-carrier ratio of 1:0.5 via solvent evaporation, exhibited an impressive four-fold increase in solubility in aqueous environments. The application of solid dispersion technology is anticipated to enhance the bioavailability and therapeutic efficacy of azilsartan medoxomil formulations. Further optimization of the formulation parameters may lead to improved drug delivery systems, ultimately benefiting the management of hypertension and related disorders. [ABSTRACT FROM AUTHOR]

The main objective of this study was to improve the aqueous solubility of Paracetamol and Domperidone using hydrotropic agents and to develop a validated method for their simultaneous estimation in pharmaceutical formulations using UV spectrophotometry. Paracetamol and Domperidone were sourced from Sigma Pharmaceuticals and Akums Pharma, respectively. Urea, sodium benzoate, niacinamide, sodium acetate, and sodium citrate were used as hydrotropic agents. The solubility of the drugs was determined using hydrotropic solutions and UV-visible spectrophotometry was employed to assess drug concentrations. Calibration curves for both drugs were prepared and regression equations were derived. The method was validated through statistical analysis of precision, recovery, and repeatability. The solubility of both Paracetamol and Domperidone improved significantly in the presence of hydrotropic agents, particularly urea (8 M). The solubility enhancement ratios were calculated, confirming the improved solubility. UV-visible spectrophotometric analysis showed linearity for Paracetamol (r² = 0.997) and Domperidone (r² = 0.995) in their respective concentration ranges. The regression equations were Y = 0.030 conc. + 0.014 for Paracetamol and Y = 0.098 conc. + 0.030 for Domperidone. The method was validated according to ICH guidelines. Recovery studies showed over 99% recovery for both drugs, indicating accuracy. Intra-day and inter-day precision, as well as analyst-to-analyst variability, were within acceptable limits (RSD < 1%). The solubility of Paracetamol and Domperidone was significantly enhanced using hydrotropic agents, with urea providing the best results. The developed UV spectrophotometric method allowed for the simultaneous estimation of both drugs, showing high precision and accuracy. The method was robust, with consistent results across different conditions and analysts. In conclusion, the study successfully enhanced the solubility of Paracetamol and Domperidone using hydrotropic agents. The developed UV spectrophotometric method for their simultaneous estimation was found to be simple, accurate and precise, making it suitable for routine analysis of pharmaceutical formulation. [ABSTRACT FROM AUTHOR]

Context: Simvastatin can be modified by the formation of multicomponent crystals to increase its solubility. Aims: To compare the solubility of multicomponent simvastatin crystals to pure simvastatin. Methods: The in silico study of simvastatin and the coformers arginine and glycine revealed non-covalent interactions, so multicomponent preparations of simvastatin crystals were prepared by solvent evaporation using a mole ratio of 1:1; 1:2 and 2:1. Results: Each simvastatin-arginine and simvastatin-glycine ratio increased the solubility, with the highest increase observed for the 1:2 ratio compared to pure simvastatin. Conclusions: Simvastatin-arginine multicomponent crystals (1:2) showed the best dissolution profile in phosphate buffer medium pH 7.0 with 67.69% dissolution, while simvastatin-glycine multicomponent crystals (1:2) exhibited the best dissolution profile in buffer media pH 1.2 with 16.19% dissolution. Characterization of the multicomponent crystals revealed a shift in the peaks, a decreased melting point, and enthalpy, indicating decreased % crystallinity and the formation of a new solid phase.

Introduction: Cannabidiol (CBD) has sparked considerable interest because of its wide range of pharmacological uses and the fact that it does not induce psychoactive effects. CBD formulation development presents significant challenges due to its limited water solubility and susceptibility to first-pass metabolism, both of which restrict its overall bioavailability. The current research aimed to use hot-melt extrusion (HME) technology to develop mucoadhesive buccal films to improve CBD solubility and reduce first-pass metabolism. Methods: Five formulations containing 10% w/w CBD were extruded using a counter-rotating twin-screw extruder (Haake Minilab II, Thermo Fisher Scientific). Different characterization studies were conducted on the developed formulations. Results: Differential scanning calorimetry (DSC) revealed that the CBD endothermic peak disappeared in some of the developed films, indicating that CBD was converted from crystalline to amorphous form. A bio-adhesion study showed that the formulations containing Carbopol® (BF2, BF3, BF4, and BF5) had higher adhesiveness properties. In vitro release and solubility studies showed an increase in CBD release and water solubility in the developed formulations when compared to pure CBD. Stability studies revealed that CBD content and release in the lead formulation (BF2) was stable over 15 months. Conclusion: The current study demonstrates that HME was successfully used as an approach to develop CBD mucoadhesive buccal films and CBD solubility was enhanced.

Abstract Limited solubility is the main cause of the low local availability of anti-candidiasis drug, miconazole nitrate (MN). The study’s objective was to develop and characterize microemulsion (ME) based temperature-triggered in situ gel of MN for intravaginal administration to enhance local availability and antifungal activity. The solubility of MN was initially studied in different oils, surfactants, and co-surfactants. Then, pseudo-ternary phase diagrams were constructed to select the best ratio of various components. The ME formulations were characterized by thermodynamic study, droplet size, polydispersity index (PDI), viscosity, and in-vitro antifungal mean inhibition zone (MIZ). Selected MEs were incorporated into different in situ gel bases using a combination of two thermosensitive polymers (poloxamer (PLX) 407 and 188), with 0.6% of hydroxypropyl methylcellulose (HPMC K4M) and gellan gum (GG) as mucoadhesive polymer. ME-based gels (MG) were investigated for gelation temperature, gelation time, viscosity, spreadability, mucoadhesive strength, in vitro release profile, and MIZ test. Furthermore, the optimum MG was assessed for in vivo animal irritation test and FESEM investigation. Tea tree oil, lavender oil, tween 80, and propylene glycol (PG) were chosen for ME preparation for the optimal formulation; formulation ME7 and ME10 were chosen. After incorporation of the selected formulation into a mixture of P407 and P188 (18:2% w/w) with 0.6% mucoadhesive polymer, the resultant MG formulation (MG1) revealed optimum gelation temperature (33 ± 0.01℃) and appropriate viscosity with enhanced sustained release (98%) and retention through sheep vaginal mucosa, MG1 exhibited a better MIZ compared to the 2% MN gel formulation and the marketed MN product, and no rabbit vagina irritation. In conclusion, the miconazole nitrate-loaded MG-based formula sustained the duration of action and better antifungal activity than the marketed miconazole nitrate formulation.

Abstract Improved solubility and anti-inflammatory (AI) properties are imperative for enhancing the effectiveness of poorly water-soluble drugs, particularly non-steroidal anti-inflammatory drugs (NSAIDs). To address these critical issues, our focus is on obtaining NSAID materials in the form of inclusion complexes (IC) with methyl-beta-cyclodextrin (MCD). Ketoprofen (KTP) is selected as the NSAID for this study due to its potency in treating various types of pain, inflammation, and arthritis. Our objective is to tackle the solubility challenge followed by enhancing the AI activity. Confirmation of complexation is achieved through observing changes in the absorbance and fluorescence intensities of KTP upon the addition of MCD, indicating a 1:1 stoichiometric ratio. Phase solubility studies demonstrated improved dissolution rates after the formation of ICs. Further analysis of the optimized IC is conducted using FT-IR, NMR, FE-SEM, and TG/DTA techniques. Notable shifts in chemical shift values and morphological alterations on the surface of the ICs are observed compared to their free form. Most significantly, the IC exhibited superior AI and anti-arthritic (AA) activity compared to KTP alone. These findings highlight the potential of ICs in expanding the application of KTP, particularly in pharmaceuticals, where enhanced stability and efficacy of natural AIs and AAs are paramount.

Improved solubility and anti-inflammatory (AI) properties are imperative for enhancing the effectiveness of poorly water-soluble drugs, particularly non-steroidal anti-inflammatory drugs (NSAIDs). To address these critical issues, our focus is on obtaining NSAID materials in the form of inclusion complexes (IC) with methyl-beta-cyclodextrin (MCD). Ketoprofen (KTP) is selected as the NSAID for this study due to its potency in treating various types of pain, inflammation, and arthritis. Our objective is to tackle the solubility challenge followed by enhancing the AI activity. Confirmation of complexation is achieved through observing changes in the absorbance and fluorescence intensities of KTP upon the addition of MCD, indicating a 1:1 stoichiometric ratio. Phase solubility studies demonstrated improved dissolution rates after the formation of ICs. Further analysis of the optimized IC is conducted using FT-IR, NMR, FE-SEM, and TG/DTA techniques. Notable shifts in chemical shift values and morphological alterations on the surface of the ICs are observed compared to their free form. Most significantly, the IC exhibited superior AI and anti-arthritic (AA) activity compared to KTP alone. These findings highlight the potential of ICs in expanding the application of KTP, particularly in pharmaceuticals, where enhanced stability and efficacy of natural AIs and AAs are paramount. [ABSTRACT FROM AUTHOR]

Human interferon gamma (hIFN-γ) plays a pivotal role as a soluble cytokine with diverse functions in both innate and adaptive immunity. In a previous investigation, we pinpointed three critical amino acid residues, i.e., threonine (T) 27, phenylalanine (F) 29, and leucine (L) 30, on the IFN-γ structure, which are integral to the epitope recognized by anti-IFN-γ autoantibodies. It is crucial to impede the interaction between this epitope and autoantibodies for effective therapy in adult-onset immunodeficiency (AOID). However, the challenge arises from the diminished solubility of the T27AF29L30A mutant in Escherichia coli BL21(DE3). This study delves into a targeted strategy aimed at improving the soluble expression of IFN-γ T27AF29AL30A. This is achieved through the utilization of five chaperone plasmids: pG-KJE8, pKJE7, pGro7, pG-Tf2, and pTf16. These plasmids, encoding cytoplasmic chaperones, are co-expressed with the IFN-γ mutant in E. coli BL21(DE3), and we meticulously analyze the proteins in cell lysate and inclusion bodies using SDS-PAGE and Western blotting. Our findings reveal the remarkable efficacy of pG-KJE8, which houses cytoplasmic chaperones DnaK-DnaJ-GrpE and GroEL-GroES, in significantly enhancing the solubility of IFN-γ T27AF29AL30A. Importantly, this co-expression not only addresses solubility concerns but also preserves the functional dimerized structure, as confirmed by sandwich ELISA. This promising outcome signifies a significant step forward in developing biologic strategies for AOID. [ABSTRACT FROM AUTHOR]

Nanosponges are versatile carriers due to their exceptional capability to improve the solubility of poorly water-soluble drugs, taste masking and enhancement of stability. This study investigates potential of nanosponges, prepared by crosslinking β-cyclodextrin with diphenyl carbonate in 1:4 ratio for enhancing solubility of Efonidipine. Nanosponges were characterized in terms of particle size. Phase solubility studies and solution state interaction studies were employed to understand the nature and strength of drug: nanosponge complexation. Complexes were prepared by kneading method and spray drying. Saturation solubility, in vitro dissolution studies and molecular modeling studies were performed. Complexes were characterized by differential scanning calorimetry (DSC), infrared spectroscopy, X ray powder diffraction (XRPD) and scanning electron microscopy. Phase solubility studies revealed 1:2 complexation between drug and carriers. Saturation solubility studies showed significant solubility increase with both beta CD and nanosponges. The increase was higher in case of spray dried complexes in all media. An 18 fold increase was observed in case of spray dried complexes in distilled water. DSC and PXRD confirmed amorphization of drug in the complexes. Thus solubility enhancement of EFD could be attributed to complexation and amorphization. Molecular modeling studies revealed the mode of entrapment of efonidipine in the carriers. In conclusion the versatility of nanosponges in encapsulating both hydrophilic and hydrophobic drug molecules holds immense promise for personalized medicine and targeted therapy, ultimately leading to improved patient outcomes. Moreover, the study introduces the efficacy of spray drying as a scalable and practical approach to maximize the solubility-enhancing benefits of nanosponges. This research highlights the potential of nanosponges to overcome a fundamental challenge in pharmaceuticals, opening new avenues for drug delivery and therapeutic advancement. [ABSTRACT FROM AUTHOR]

Major depression is a prevalent disorder characterized by sadness, lack of interest or pleasure, interrupted sleep or food, and impaired concentration. Mirtazapine (MTZ), a tetracyclic antidepressant drug, is commonly used to treat moderate to severe depression. MTZ is classified as a BCS class II drug that has shown bioavailability of 50% due to extensive first-pass metabolism. The aim of this research is to develop a delivery platform with enhanced solubility and oral bioavailability of MTZ through formulating polymeric micelles modeled in a rapid release tablet. Mirtazapine loaded polymeric micelles (MTZ-PMs) were formulated to enhance the solubility. Solutol® HS 15 and Brij 58 were used as combined surfactants in a ratio of (20:1) to MTZ in addition to Transcutol® P as a penetration enhancer. The following in vitro tests were performed: particle size, PDI, zeta potential, solubility factor, stability index, and transmission electron microscopes. Afterward, MTZ-PMs were converted to dry free flowable powder through loading on the adsorptive surface of Aerosil 200; then, the powder mixture was directly compressed (MTZ-PMs-RRT) into 13 mm tablets. MTZ-PMs-RRT was further investigated using in vitro evaluation tests of the tablets, namely, weight variation, thickness, diameter, hardness, friability, disintegration time, drug content, and in vitro dissolution test, which complied with the pharmacopeial limits. The pharmacokinetic parameters of MTZ-PMs-RRT compared to Remeron® tablet were further investigated in rabbits. The results showed enhanced solubility of MTZ with improved percentage relative bioavailability to 153%. The formulation of MTZ in the form of MTZ-PMs-RRT successfully improved the solubility, stability, and bioavailability of MTZ using a simple and scalable manufacturing process. [ABSTRACT FROM AUTHOR]

In the conducted research study, solubility investigation was performed to elucidate the dissolution rate and behaviour of a drug incorporated within a solid dispersion matrix. The foremost objective was to appraise the impact of formulation parameters on the improvement of drug's solubility, the list of factors influencing the bioavailability. To this end, a systematic series of experiments were undertaken, wherein the drug was co-precipitated with a hydrophilic polymer carrier using various solvent systems and ratios. The resulting solid dispersions were meticulously characterized, employing state-ofthe-art analytical techniques. Subsequently, solubility profiles were generated through equilibrium solubility studies, encompassing a range of pH conditions and temperatures, to comprehensively evaluate the dissolution behaviour of the drug. Based on study, it was concluded that the solubility of Pazopanib Hydrochloride (Pazopanib base) is significantly increased from 0.001 mg/ml to ~8.000 mg/ml. the same was confirmed from the analytical tools. Analytical tools also confirm the conversion of crystalline form to amorphous form. The outcomes of these investigations provide essential insights into the potential utility of solid dispersion systems as a viable strategy for enhancing the solubility and, consequently, the therapeutic efficacy of the drug in question. [ABSTRACT FROM AUTHOR]

AbstractIntermolecular hydrogen bonding plays a pivotal role in the stability and efficacy of drug-polymer mixtures, which are essential components in modern drug delivery systems. The knowledge of prominent interactions might provide a means to optimize the physiochemical stability of the developed targeted system. Hence, this review explores the fundamental principles of hydrogen bonding in drug-polymer interactions which can significantly influence the solubility, stability and release profiles of pharmaceutical formulations. The review provides an in-depth examination of the types of functional groups that participate in hydrogen bonding, the characterization techniques employed to study these interactions and the implications of hydrogen bonding on drug delivery. Case studies of successful drug-polymer systems stabilized by hydrogen bonding are presented, highlighting the practical applications and challenges associated with these formulations. Furthermore, the review discusses the future perspectives in this field, including the design of novel polymers and the integration of computational modeling to predict hydrogen bonding behavior. By understanding and leveraging hydrogen bonding, researchers can optimize drug delivery systems, ensuring enhanced bioavailability, controlled release and improved patient outcomes. This review aims to serve as a comprehensive resource for pharmaceutical scientists and formulators, offering insights into the strategic use of hydrogen bonding to develop more effective and stable drug delivery systems. [ABSTRACT FROM AUTHOR]

In this study, a novel oral formulation of berberine hydrochloride (BBH) hydrogel was successfully synthesized through physical cross-linking using chitosan (CS) and carboxymethyl-β-cyclodextrin (CMCD). The characterization results confirmed the successful synthesis of the CS/CMCD hydrogel and the subsequent loading of BBH into this composite (CS/CMCD/BBH) was effectively accomplished. The BBH was used as a model drug and the resulting hydrogel demonstrated a sustained drug release profile. In addition to its improved solubility and sustained release characteristics, the hydrogel exhibited excellent antibacterial activity against common pathogens such as Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), and Candida albicans (C. albicans). Additionally, in vitro studies indicated that the hydrogel was not cytotoxic to NIH3T3 and HaCaT cells, suggesting its safety for biomedical applications. This lack of cytotoxic effects, combined with the mechanical strength, solubility improvements, and antibacterial properties of the hydrogel, positions the CS/CMCD/BBH hydrogel as a promising candidate for the effective oral delivery of BBH. By addressing the solubility and delivery challenges of BBH, this hydrogel offers a viable solution for the oral administration of BBH, with potential applications in various biomedical fields. [ABSTRACT FROM AUTHOR]

[Display omitted] • Presenting a universal carrier designed to address issues like inadequate solubility, limited targeting, and complex preparation processes for a variety of anticancer drugs. • The as-prepared SN38-GY-CCYRGD nanoparticles exhibit greatly improved solubility, targeting efficacy and enhanced anticancer effectiveness. • Pioneering an innovative delivery method, seamlessly integrating efficient and secure techniques into a unified carrier system, custom-designed for hydrophobic anticancer drugs. The current state of drug delivery systems allows for the resolution of specific issues like inadequate solubility, limited targeting capabilities, and complex preparation processes, requiring tailored designs for different drugs. Yet, the major challenge in clinical application lies in surmounting these obstacles with a universal carrier that is effective for a variety of anticancer drugs. Herein, with the help of computer simulation, we rationally design ultrashort peptides GY and CCYRGD, which can co-assemble with hydrophobic anticancer drugs into nanoparticles with enhanced solubility, targeting ability and anticancer efficacy. Taking 7-ethyl-10-hydroxy camptothecin (SN38) as a model anticancer drug, the co-assembled SN38-GY-CCYRGD nanoparticles significantly enhance the water solubility of SN38 by more than three orders of magnitude. The as-prepared nanoparticles can effectively kill cancer cells, e.g., human small cell lung cancer (A549) cells with a notable cell mortality rate of 71%. Mice experimental results demonstrate the nanoparticles' efficient targeting capability, marked reducing the toxicity to normal tissues while improving antitumor efficacy. This work presents a novel drug delivery method, integrating effective, targeted, and safe strategies into a comprehensive carrier system, designed for the administration of hydrophobic anticancer drugs. [ABSTRACT FROM AUTHOR]

Purpose: Twin-screw wet granulation (TSWG) is a manufacturing process that offers several advantages for the processing of water-insoluble active pharmaceutical ingredients (APIs) and has been used for increasing the solubility and dissolution rates. Here we introduce a novel TSWG approach with reduced downstream processing steps by using non-volatile solvents as granulating binders. Methods: Herein, TSWG was carried out using Transcutol a non-volatile protic solvent as a granulating binder and dissolution enhancer of ibuprofen (IBU) blends with cellulose polymer grades (Pharmacoat® 603, Affinisol™, and AQOAT®). Results: The physicochemical characterisation of the produced granules showed excellent powder flow and the complete transformation of IBU into the amorphous state. Dissolution studies presented immediate release rates for all IBU formulations due to the high drug-polymer miscibility and the Transcutol solubilising capacity. Conclusions: Overall, the study demonstrated an innovative approach for the development of extruded granules by processing water-insoluble APIs with non-volatile solvents for enhanced dissolution rates at high drug loadings. [ABSTRACT FROM AUTHOR]

PROTACs, proteolysis targeting chimeras, are bifunctional molecules inducing protein degradation through a unique proximity-based mode of action. While offering several advantages unachievable by classical drugs, PROTACs have unfavorable physicochemical properties that pose challenges in application and formulation. In this study, we show the solubility enhancement of two PROTACs, ARV-110 and SelDeg51, using Poly(vinyl alcohol). Hereby, we apply a three-fluid nozzle spray drying set-up to generate an amorphous solid dispersion with a 30% w/w drug loading with the respective PROTACs and the hydrophilic polymer. Dissolution enhancement was achieved and demonstrated for t = 0 and t = 4 weeks at 5 °C using a phosphate buffer with a pH of 6.8. A pH shift study on ARV-110-PVA is shown, covering transfer from simulated gastric fluid (SGF) at pH 2.0 to fasted-state simulated intestinal fluid (FaSSIF) at pH 6.5. Additionally, activity studies and binding assays of the pure SelDeg51 versus the spray-dried SelDeg51-PVA indicate no difference between both samples. Our results show how modern enabling formulation technologies can partially alleviate challenging physicochemical properties, such as the poor solubility of increasingly large 'small' molecules. [ABSTRACT FROM AUTHOR]

The aim of the research was to investigate and compare the interaction between flavanones (flavanone, 4-chloro-flavanone) with potential anticancer activity and selected cyclodextrins. Measurements were made using calorimetric (ITC, DSC) and spectrophotometric (UV-Vis spectroscopy, FT-IR, 1H NMR) methods. The increase in the solubility in aqueous medium caused by the complexation process was determined by the Higuchi-Connors method. As a result of the study, the stoichiometry and thermodynamics of the complexation reaction were determined. The formation of stable inclusion complexes at a 1:1 M ratio between flavanone and 4-chloroflavanone and the cyclodextrins selected for research was also confirmed. [ABSTRACT FROM AUTHOR]

Lutein is an oxygenated fat-soluble carotenoid and a functional compound with proven health benefits for the human body. Nevertheless, the poor water solubility and low oral bioavailability of lutein greatly limit its application. To address this, we developed an effective approach to enhance the water solubility of lutein through co-amorphous formulation. Specifically, the lutein-sucralose co-amorphous mixture was prepared at a molar ratio of 1:1 using ethanol and water as solvents by employing the solvent evaporation method, followed by solid-state characterization and dissolution testing conducted to assess the properties of the formulation. The X-ray diffraction pattern with an amorphous halo and the differential scanning calorimetry thermogram with no sharp melting peaks confirmed the formation of a binary co-amorphous system. Changes in peak shape, position, and intensity observed in the Fourier transform infrared spectroscopy spectrum revealed intermolecular interactions between lutein and sucralose molecules, while molecular dynamics simulations identified interaction sites between their hydroxyl groups. Additionally, dissolution testing demonstrated better dissolution performance of lutein in the co-amorphous form compared to pure lutein and physical mixture counterparts. Our findings present a novel strategy for improving the water solubility of lutein to make better use of it. [ABSTRACT FROM AUTHOR]

In the past, the administration of medicines for children mainly involved changes to adult dosage forms, such as crushing tablets or opening capsules. However, these methods often led to inconsistent dosing, resulting in under- or overdosing. To address this problem and promote adherence, numerous initiatives, and regulatory frameworks have been developed to develop more child-friendly dosage forms. In recent years, multiparticulate dosage forms such as mini-tablets, pellets, and granules have gained popularity. However, a major challenge that persists is effectively masking the bitter taste of drugs in such formulations. This review therefore provides a brief overview of the current state of the art in taste masking techniques, with a particular focus on taste masking by film coating. Methods for evaluating the effectiveness of taste masking are also discussed and commented on. Another important issue that arises frequently in this area is achieving sufficient dissolution of poorly water-soluble drugs. Since the simultaneous combination of sufficient dissolution and taste masking is particularly challenging, the second objective of this review is to provide a critical summary of studies dealing with multiparticulate formulations that are tackling both of these issues.

Olmesartan medoxomil (OLM) is a selective angiotensin II receptor antagonist used in the treatment of hypertension. Its therapeutic potential is limited by its poor water solubility, leading to poor bioavailability. Encapsulation of the drug substance by two methylated cyclodextrins, namely randomly methylated β-cyclodextrin (RM-β-CD) and heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin (TM-β-CD), was carried out to overcome the limitation related to OLM solubility, which, in turn, is expected to result in an improved biopharmaceutical profile. Supramolecular entities were evaluated by means of thermoanalytical techniques (TG—thermogravimetry; DTG—derivative thermogravimetry), spectroscopic methods including powder X-ray diffractometry (PXRD), universal-attenuated total reflectance Fourier-transform infrared (UATR-FTIR) and UV spectroscopy, saturation solubility studies, and by a theoretical approach using molecular modeling. The phase solubility method reveals an AL-type diagram for both inclusion complexes, indicating a stoichiometry ratio of 1:1. The values of the apparent stability constant indicate the higher stability of the host–guest system OLM/RM-β-CD. The physicochemical properties of the binary systems are different from those of the parent compounds, emphasizing the formation of inclusion complexes between the drug and CDs when the kneading method was used. The molecular encapsulation of OLM in RM-β-CD led to an increase in drug solubility, thus the supramolecular adduct can be the subject of further research to design a new pharmaceutical formulation containing OLM, with improved bioavailability. [ABSTRACT FROM AUTHOR]

The objective of this study was to design and develop an Agarose-based polymeric nanogel network system for solubility enhancement of a lipophilic drug, Dexibuprofen. Polymeric nanogels were synthesized through free radical polymerization where Agarose was cross-linked with 2-Acrylamido-2-methylpropane sulfonic acid (AMPS) in the presence of ammonium persulfate (APS) as an initiator and N, N'-Methylenebisacrylamide (MBA) as crosslinking agent. The resulting polymeric nanogels underwent a comprehensive characterization process including Fourier transform infrared (FTIR), particle size analysis, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), thermal gravimetric analysis (TGA), powder X-ray diffraction (PXRD), and swelling studies to confirm the preparation of a stable polymeric nanogel system. FTIR spectral findings revealed that Agarose was chemically cross-linked with AMPS and confirmed the successful insertion of AMPS chains on the Agarose backbone. Particle size analysis revealed a diameter of 168 nm with a zeta potential of −9.91 mV, providing assurance of a stable polymeric nanogel system. SEM images depicted a highly porous surface. DSC and TGA results showed a more thermally stable network system than individual ingredients. Swelling studies revealed an increased swelling ratio of polymeric nanogels at phosphate buffer of pH 6.8 than acidic buffer of pH 1.2. Dexibuprofen was efficiently loaded into a polymeric nanogel system with a high entrapment efficiency of up to 80%. The solubility of the drug was enhanced when introduced to a polymeric nanogel formulation when compared to pure drug. The system reproducibility was evaluated through in vitro drug release and kinetic modeling of drug release. Toxicity studies confirmed the formulation's effectiveness, showcasing the developed polymeric nanogels as a promising option for delivering lipophilic drugs, with outstanding physicochemical properties, improved solubility, and minimal oral toxicity. [ABSTRACT FROM AUTHOR]

Inadequate bioavailability of therapeutic drugs, which is often the consequence of their unacceptable solubility and dissolution rates, is an indisputable operational challenge of pharmaceutical companies due to its detrimental effect on the therapeutic efficacy. Over the recent decades, application of supercritical fluids (SCFs) (mainly SCCO2) has attracted the attentions of many scientists as promising alternative of toxic and environmentally-hazardous organic solvents due to possessing positive advantages like low flammability, availability, high performance, eco-friendliness and safety/simplicity of operation. Nowadays, application of different machine learning (ML) as a versatile, robust and accurate approach for the prediction of different momentous parameters like solubility and bioavailability has been of great attentions due to the non-affordability and time-wasting nature of experimental investigations. The prominent goal of this article is to review the role of different ML-based tools for the prediction of solubility/bioavailability of drugs using SCCO2. Moreover, the importance of solubility factor in the pharmaceutical industry and different possible techniques for increasing the amount of this parameter in poorly-soluble drugs are comprehensively discussed. At the end, the efficiency of SCCO2 for improving the manufacturing process of drug nanocrystals is aimed to be discussed.

The major aim of the current study is to develop a data-driven methodology based on green processing for estimation of drug solubility in supercritical carbon dioxide as the solvent. Several machine learning algorithms were utilized to simulate Capecitabine solubility in supercritical carbon dioxide for green pharmaceutical manufacturing applications which can enhance the solubility of drugs by this method of processing. In the models, the inputs are pressure (P) and temperature (T), and the target output (Y) is solubility. Tree-based ensemble models of RF (Random Forest), ET (Extra Tree), and GB (Gradient Boosting) were selected for modeling in this research in combination with the optimizer to model the process. The hyper-parameters of models were optimized to reduce the error in the fitting. The coefficient of determination (R2 score) values obtained more than 0.96 and RMSE (root mean square error) for ET, GB, and RF models are 2.91, 2.37, and 4.45, respectively. Based on accurate analyses of results Gradient Boosting selected for primary model in this research. The models were able to estimate the drug solubility which can be used to estimate solubility for a wide range, thereby saving time and costs of measurements.

Suryani Suryani,1,2 Anis Yohana Chaerunisaa,3,4 I Made Joni,5,6 Ruslin Ruslin,2 Vica Aspadiah,2 Anton Anton,7 Ari Sartinah,2 La Ode Ahmad Nur Ramadhan8 1Doctor of Pharmacy Study Program, Faculty of Pharmacy, Padjadjaran University, Sumedang, Indonesia; 2Department of Pharmacy, Faculty of Pharmacy, Halu Oleo University, Kendari, Indonesia; 3Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Padjadjaran University, Sumedang, Indonesia; 4Dosage Form Development Research Centre, Faculty of Pharmacy, Padjadjaran University, Sumedang, Indonesia; 5Department of Physics, Faculty of Mathematics and Natural Sciences, Padjadjaran University, Sumedang, Indonesia; 6Functional Nano Powder University Centre of Excellence, Padjadjaran University, Sumedang, Indonesia; 7Department of Biology, Faculty of Mathematics and Natural Sciences, Halu Oleo University, Kendari, Indonesia; 8Department of Chemistry, Faculty of Mathematics and Natural Sciences, Halu Oleo University, Kendari, IndonesiaCorrespondence: Anis Yohana Chaerunisaa; Suryani Suryani, Email anis.yohana.chaerunisaa@unpad.ac.id; Suryani20001@mail.unpad.ac.idAbstract: Chitosan is a functional polymer in the pharmaceutical field, including for nanoparticle drug delivery systems. Chitosan-based nanoparticles are a promising carrier for a wide range of therapeutic agents and can be administered in various routes. Solubility is the main problem for its production and utilization in large-scale industries. Chitosan modifications have been employed to enhance its solubility, including chemical modification. Many reviews have reported the chemical modification but have not focused on the specific characteristics obtained. This review focused on the modification to improve chitosan solubility. Additionally, this review also focused on the application of chitosan derivatives in nanoparticle drug delivery systems since very few similar reviews have been reported. The specific method for chitosan derivative-based nanoparticles was also reported and the latest report of chitosan, chitosan derivative, and chitosan toxicity were also described. Keywords: polymer, chitosan derivatives, solubility enhancement, drug delivery system

Dunaliella salina has been recognized as an excellent biomass source of carotenoid, which can be used as a natural orange coloring agent for food products. The most eco-friendly approach for extracting carotenoid is through supercritical carbon dioxide extraction, as it yields highly concentrated extracts while preventing pigment thermal degradation. However, there are limitations when a lipophilic extract is considered a food ingredient, in particular very difficult handling and low solubility in water-based products. The aim of this study was to develop a hydrosoluble form of a natural carotenoid-rich extract recovered from algae biomass within a biorefinery concept to be incorporated in aqueous-based food products. A two-step process was developed, starting with the emulsification of the supercritical extract into a mixture of maltodextrin and gum arabic, using soy lecithin as an emulsifier. The emulsification was followed by a spray-drying step. The impact of process variables on the encapsulation yield, efficiency, emulsion properties, and particle characteristics was studied. The resulting particles exhibited an intense orange color and good water dispersibility, facilitating uniform yellow coloring when incorporated into an aqueous-based product. Overall, spray-drying emulsions containing carotenoids derived from Dunaliella salina prove to be a promising strategy for the global market demand for natural colorants.

Background/Objectives: Amorphization of an active pharmaceutical ingredient (API) can improve its dissolution and enhance bioavailability. Avoiding solvents for drug amorphization is beneficial due to environmental issues and potential solvent residues in the final product. Methods: Dry amorphization using a twin-screw extruder is presented in this paper. A blend of mesoporous silica particles and crystalline itraconazole was processed using a pharma-grade laboratory scale twin-screw extruder. The influence of different screw configurations and process parameters was tested. Particle size and shape are compared in scanning electron microscopy (SEM) images. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) are used to determine the residual amount of crystalline itraconazole in the final product. Results: An optimized screw configuration for the process was found which leads to more than 90% amorphous API when processed at room temperature. Full amorphization was reached at 70 °C. The specific mechanic energy (SME) introduced into the material during twin-screw processing is crucial for the dry amorphization. The higher the SME, the lower the residual amount of crystalline API. Two months after processing, however, recrystallization was observed by XRD. Conclusions: Dry processing using a twin-screw extruder is continuous, free of solvents and can be performed at low temperatures. This study proves the concept of twin-screw processing with mesoporous silica for dry amorphization of itraconazole.

Oils and lipids help make water-insoluble drugs soluble by dispersing them in an aqueous medium with the help of a surfactant and enabling their absorption across the gut barrier. The emergence of microemulsions (thermodynamically stable), nanoemulsions (kinetically stable), and self-emulsifying drug delivery systems added unique characteristics that make them suitable for prolonged storage and controlled release. In the 1990s, solid-phase lipids were introduced to reduce drug leakage from nanoparticles and prolong drug release. Manipulating the structure of emulsions and solid lipid nanoparticles has enabled multifunctional nanoparticles and the loading of therapeutic macromolecules such as proteins, nucleic acid, vaccines, etc. Phospholipids and surfactants with a well-defined polar head and carbon chain have been used to prepare bilayer vesicles known as liposomes and niosomes, respectively. The increasing knowledge of targeting ligands and external factors to gain control over pharmacokinetics and the ever-increasing number of synthetic lipids are expected to make lipid nanoparticles and vesicular systems a preferred choice for the encapsulation and targeted delivery of therapeutic agents. This review discusses different lipids and oil-based nanoparticulate systems for the delivery of water-insoluble drugs. The salient features of each system are highlighted, and special emphasis is given to studies that compare them.

Objectives: The study explores the potential of various deep eutectic solvents (DESs) to serve as drug delivery systems and pharmaceutical excipients. The research focuses on two primary objectives: evaluating the ability of the selected DES systems to enhance the solubility of two poorly water-soluble model drugs (IBU and MFA), and evaluating their physicochemical properties, including density, viscosity, flow behavior, surface tension, thermal stability, and water dilution effects, to determine their suitability for pharmaceutical applications. Methods: A range of DES systems containing pharmaceutically acceptable constituents was explored, encompassing organic acid-based, sugar- and sugar alcohol-based, and hydrophobic systems, as well as menthol (MNT)-based DES systems with common pharmaceutical excipients. MNT-based DESs exhibited the most significant solubility enhancements. Results: IBU solubility reached 379.69 mg/g in MNT: PEG 400 (1:1) and 356.3 mg/g in MNT:oleic acid (1:1), while MFA solubility peaked at 17.07 mg/g in MNT:Miglyol 812®N (1:1). In contrast, solubility in hydrophilic DES systems was significantly lower, with choline chloride: glycerol (1:2) and arginine: glycolic acid (1:8) showing the best results. While demonstrating lower solubility compared to the MNT-based systems, sugar-based DESs exhibited increased tunability via water and glycerol addition both in terms of solubility and physicochemical properties, such as viscosity and surface tension. Conclusions: Our study introduces novel DES systems, expanding the repertoire of pharmaceutically acceptable DES formulations and opening new avenues for the rational design of tailored solvent systems to overcome solubility challenges and enhance drug delivery.

Dunaliella salina has been recognized as an excellent biomass source of carotenoid, which can be used as a natural orange coloring agent for food products. The most eco-friendly approach for extracting carotenoid is through supercritical carbon dioxide extraction, as it yields highly concentrated extracts while preventing pigment thermal degradation. However, there are limitations when a lipophilic extract is considered a food ingredient, in particular very difficult handling and low solubility in water-based products. The aim of this study was to develop a hydrosoluble form of a natural carotenoid-rich extract recovered from algae biomass within a biorefinery concept to be incorporated in aqueous-based food products. A two-step process was developed, starting with the emulsification of the supercritical extract into a mixture of maltodextrin and gum arabic, using soy lecithin as an emulsifier. The emulsification was followed by a spray-drying step. The impact of process variables on the encapsulation yield, efficiency, emulsion properties, and particle characteristics was studied. The resulting particles exhibited an intense orange color and good water dispersibility, facilitating uniform yellow coloring when incorporated into an aqueous-based product. Overall, spray-drying emulsions containing carotenoids derived from Dunaliella salina prove to be a promising strategy for the global market demand for natural colorants. [ABSTRACT FROM AUTHOR]

The aim of this work was to study the possibility to use SepitrapTM as a carrier for the formulation of amorphous solid dispersions by HME (hot melt extrusion) processing aiming solubility enhancement of poorly water-soluble drugs. SepitrapTM is a microencapsulated powder solubilizer designed to simplify the manufacture of drugs in oral solid forms, not yet tested for this purpose. The performance of SepitrapTM was evaluated in HME processing for amorphous solid dispersions of poorly-water soluble drugs with indomethacin as a model drug. The study was conducted using a twin-screw extruder, two compositions of SepitrapTM and different loads of indomethacin, demonstrating that SepitrapTM could represent a new range of carriers for amorphous solid dispersions for HME processing, reducing necessary downstream steps such as grinding. [ABSTRACT FROM AUTHOR]

The application of hydrogels for anti-cancer drug delivery has garnered considerable interest in the medical field. Current cancer treatment approaches, such as chemotherapy and radiation therapy, often induce severe side effects, causing significant distress and substantial health complications to patients. Hydrogels present an appealing solution as they can be precisely injected into specific sites within the body, facilitating the sustainable release of encapsulated drugs. This localized treatment approach holds great potential for reducing toxicity levels and improving drug delivery efficacy. In this study we developed a hydrogel delivery system containing polyamidoamine (PAMAM) dendrimer and polyethylene glycol (PEG) for solubility enhancement and sustained delivery of hydrophobic anti-cancer drugs. The three selected model drugs, e.g. silibinin, camptothecin, and methotrexate, possess limited aqueous solubility and thus face restricted application. In the presence of vinyl sulfone functionalized PAMAM dendrimer at 45 mg/mL concentration, drug solubility is increased by 37-fold, 4-fold, and 10-fold for silibinin, camptothecin, and methotrexate, respectively. By further crosslinking of the functionalized PAMAM dendrimer and thiolated PEG, we successfully developed a fast-crosslinking hydrogel capable of encapsulating a significant payload of solubilized cancer drugs for sustained release. In water, the drug encapsulated hydrogels release 30%–80% of their loads in 1–4 days. MTT assays of J82 and MCF7 cells with various doses of drug encapsulated hydrogels reveal that cytotoxicity is observed for all three drugs on both J82 and MCF7 cell lines after 48 h. Notably, camptothecin exhibits higher cytotoxicity to both cell lines than silibinin and methotrexate, achieving up to 95% cell death at experimental conditions, despite its lower solubility. Our experiments provide evidence that the PAMAM dendrimer-mediated hydrogel system significantly improves the solubility of hydrophobic drugs and facilitates their sustained release. These findings position the system as a promising platform for controlled delivery of hydrophobic drugs for intratumoral cancer treatment. [ABSTRACT FROM AUTHOR]

An amorphous fiber-based solid dispersion of chlorzoxazone was prepared for the first time by employing centrifugal spinning, using polyvinylpyrrolidone as the fiber-forming polymer. After optimization of the spinning parameters, the obtained fibers were characterized using a set of analytical techniques, both in a solid- and solution-state. Morphological characterization revealed a slightly aligned, defect-free fibrous structure with an average fiber diameter of d = 3.07 ± 1.32 μm. The differential scanning calorimetric results indicated a crystalline-to-amorphous transition of the active substance during the centrifugal spinning process, while gas chromatographic determinations revealed a residual ethanol content of 0.42 ± 0.04%. UV spectroscopy indicated the incorporation of chlorzoxazone in the fibrous structures, with an average active substance content of 15.91 ± 0.36 w/w%. During small-volume dissolution studies, the prepared fiber mats presented immediate disintegration upon contact with the dissolution media, followed by rapid dissolution of the active substance, with 84.8% dissolved at 1 min and 93.7% at 3 min, outperforming the micronized, pure chlorzoxazone. The obtained results indicate that centrifugal spinning is a low-cost, high-yield, viable alternative to the currently used methods to prepare fiber-based amorphous solid dispersions of poorly soluble drugs. The prepared chlorzoxazone-loaded microfibers could be used as a buccal dosage form for the systematic delivery of chlorzoxazone and could potentially lead to a rapid onset of action and longer efficacy of the muscle relaxant drug. [ABSTRACT FROM AUTHOR]

The primary objective of this study was to develop a rapidly dissolving tablet containing an antihypertensive drug, candesartan cilexetil (CAND). The research work focused on improving solubility and in vitro dissolution of drugs using spherical agglomeration technique. Spherical agglomerates of CAND were developed using PVPK-30 as polymer and dichloromethane as bridging liquid. A spherical agglomerate of CAND was used to formulate fast dissolving tablet (FDT) with different superdisintegrants like Crospovidone and Cross carmellose sodium. The prepared powder blend was evaluated for different pre-compression parameters like solubility, compressibility index, Hausner's ratio and flow property and post-compression parameters including in vitro dissolution study. The solubility of prepared agglomerates was found to be 0.15 to 0.91 mg mL-1, and it was higher than the pure drug (0.00071 mg mL-1). In vitro drug release study of optimized batch of FDT has shown 95.47 % of drug release. From the results, it was revealed that the prepared FDT using the agglomeration technique might be used to enhance the solubility and bioavailability of CAND to augment acute and chronic hypertension therapy. [ABSTRACT FROM AUTHOR]

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Transglycosylation has been used to modify the physicochemical properties of original compounds. As a result, transglycosylated compounds can form molecular aggregates in size ranges of a few nanometers in an aqueous medium when their concentrations exceed a specific level. Incorporating these hydrophobic compounds has been observed to enhance the solubility of hydrophobic compounds into aggregate structures. Thus, this review introduces four transglycosylated compounds as food additives that can enhance the solubility and oral absorption of hydrophobic compounds. Here, transglycosylated hesperidin, transglycosylated rutin, transglycosylated naringin, and transglycosylated stevia are the focus as representative substances. Significantly, we observed that amorphous formations containing hydrophobic compounds with transglycosylated compounds improved solubility and oral absorption compared to untreated hydrophobic compounds. Moreover, combining transglycosylated compounds with hydrophilic polymers or surfactants enhanced the solubilizing effects on hydrophobic compounds. Furthermore, the enhanced solubility of hydrophobic compounds improved their oral absorption. Transglycosylated compounds also influenced nanoparticle preparation of hydrophobic compounds as a dispersant. This study demonstrated the benefits of transglycosylated compounds in developing supplements and nutraceuticals of hydrophobic compounds with poor aqueous solubility. [ABSTRACT FROM AUTHOR]

Gout is characterized by the formation of monosodium urate crystals in peripheral joints. We carried out laboratory studies to investigate the effect of adding nine different methylxanthines and two different methylated uric acid derivatives on the development of these crystals over the course of 96 h in a medium whose composition was similar to that of synovial fluid. Our results showed that 7-methylxanthine reduced or totally prevented crystal formation; 1-methylxanthine, 3-methylxanthine, 7-methyluric acid, and 1,3-dimethyluric acid had weaker effects, and the other molecules had no apparent effect. The presented results indicate that a 7-methylxanthine concentration of about 6 × 10−5 M (10 mg/L) prevented the formation of crystals for an initial urate concentration of 1.78 × 10−3 M (300 mg/L) in the presence of 0.4 M of Na+ for 96 h at 25 °C and a pH of 7.4. We attribute these results to alterations in thermodynamics, not kinetics. Our results suggest that prevention of crystallization in vivo could be achieved by direct oral administration of 7-methylxanthine or other methylxanthines that are metabolized to 7-methylxanthine. For example, the hepatic metabolism of theobromine leads to significant plasma levels of 7-methylxanthine (14% of the initial theobromine concentration) and 3-methylxanthine (6% of the initial theobromine concentration); however, 7-methyluric acid is present at very low concentrations in the plasma. It is important to consider that several of the specific molecules we examined (theobromine, caffeine, theophylline, dyphylline, etophylline, and pentoxifylline) did not directly affect crystallization. [ABSTRACT FROM AUTHOR]

One challenge in the development of new drug formulations is overcoming their low solubility in relevant aqueous media. Reducing the particle size of drug powders to a few hundred nanometers is a well‐known method that leads to an increase in solubility due to an elevated total surface area. However, state‐of‐the‐art comminution techniques like cryo‐milling suffer from degradation and contamination of the drugs, particularly when sub‐micrometer diameters are aspired that require long processing times. In this work, picosecond‐pulsed laser fragmentation in liquids (LFL) of dispersed drug particles in a liquid‐jet passage reactor is used as a wear‐free comminution technique using the hydrophobic oral model drugs naproxen, prednisolone, ketoconazole, and megestrol acetate. Particle size and morphology of the drug particles are characterized using scanning electron microscopy (SEM) and changes in particle size distributions upon irradiation are quantified using an analytical centrifuge. The findings highlight the superior fragmentation efficiency of the liquid‐jet passage reactor setup, with a 100 times higher fraction of submicrometer particles (SMP) of the drugs compared to the batch control, which enhances solubility and goes along with minimal chemical degradation (<1%), determined by attenuated total reflection‐Fourier transform infrared spectroscopy (ATR‐FTIR), high‐performance liquid chromatography (HPLC), and X‐ray diffraction (XRD). Moreover, the underlying predominantly photo‐mechanically induced laser fragmentation mechanisms of organic microparticles (MP) are discussed. [ABSTRACT FROM AUTHOR]

Purpose: The study aims to explore the potential of amorphous solid dispersion (ASD) technology in improving the solubility and bioavailability of flutamide (FLT), a poorly water-soluble drug. The introduction of beta-cyclodextrin (β-CD) is investigated as a strategy to overcome FLT's solubility limitations. Methods: The study employed various methods, including a validated UV spectrophotometric technique to assess FLT solubility and the creation of supersaturation through different β-CD and FLT combinations. Two formulation approaches, physical mixtures (PMs) and solid dispersions (SDs), were developed using freeze-drying and solvent evaporation methods. Analysis involved differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR), along with loading and release tests, including statistical analysis of dissolution profiles. Results: The FTIR analysis indicated that molecular interactions and chemical bonds remained largely unchanged. DSC results demonstrated the transformation of FLT from a crystalline to an amorphous state in the SDs. In the supersaturation test, it was evident that the solution with 30% β-CD and 70% FLT achieved a remarkable 5.69-fold increase in FLT concentration compared to the pure drug. Solid dispersion formulations exhibited varying drug release profiles, with the 30% β-CD and 70% FLT combination showing the most rapid release, reaching approximately 50% within 240 min. Conclusion: The study underscores the effectiveness of β-CD in the 30:70 β-CD to FLT combination to enhance FLT solubility and bioavailability. However, higher proportions of β-CD led to reduced drug release, potentially due to cyclodextrin aggregation, which could hinder drug interactions. [ABSTRACT FROM AUTHOR]