Computational and Experimental Approaches for HPMCAS-Based Solid Dispersions of Abiraterone Acetate: Formulation, Characterization, and Biopharmaceutical Enhancement Evaluation.

Improving the biopharmaceutical performance of azole antifungals: a comparative study of solid dispersion and co-crystallization of ketoconazole and itraconazole

Background: Oral bioavailability of BCS class II azole antifungals, ketoconazole and itraconazole, is hampered by low aqueous solubility. Improving solubility and dissolution is necessary for greater therapeutic efficacy. This research compared two approaches: solid dispersion and pharmaceutical co-crystallization to improve their biopharmaceutical properties. Methodology: Solid dispersions were prepared using the organic solvent evaporation technique with PEG-10000 for ketoconazole and HPMCE50 for itraconazole. Co-crystals with benzoic and tartaric acids were studied by FT-IR, DSC, and PXRD. Optimized formulations were compressed into tablets and analyzed for pharmacopoeial parameters, dissolution, release kinetics, and ICH stability. Results and Discussion: Saturation solubility investigations revealed that, compared to amorphization, solid dispersions exhibited more efficient enhancement due to the combined effect of amorphous enrichment and polymer solubilization. Tartaric acid co-crystals could increase solubility by crystal lattice modification. cc-Tabs showed burst release profiles, while SDs gave controlled drug release. The release of drug was in accordance with the first-order and Korsmeyer–Peppas models with anomalous transport, and was sustained for six months. The low aqueous solubility of azole antifungals restricts their oral bioavailability. The solubility and dissolution of ketoconazole and itraconazole were enhanced by solid dispersion and co-crystallization. Solid dispersions provided superior amorphous stability and extended-release, while co-crystals led to faster initial dissolution and better early drug availability. Conclusion: Both approaches were successful in improving solubility, dissolution, and stability. Both SDs modulated drug release kinetics; sustained-release profiles were obtained from the solid dispersions, and fast dissolution was favored by co-crystallization, thus providing both as viable approaches for oral delivery of poorly soluble azole antifungals.

Mechanistic Insights into Supersaturation Control of Itraconazole Amorphous Solid Dispersions Under Physiological Hydrodynamics: An Experimental and Computational Study

Solid self-microemulsifying drug delivery systems in modern pharmaceutics: design, characterization, and clinical applications

Background: Approximately 40% of marketed medicines and 70% of pipeline products exhibit poor aqueous solubility, leading to inconsistent oral bioavailability and impaired efficacy. S-SMEDDS represent a revolutionary approach for converting liquids into stable solid dosage forms. Methodology: Methods employed to prepare S-SMEDDs include adsorption onto carriers, spray drying, hot-melt extrusion, and freeze-drying. Characterization includes assessing self-emulsifying behavior, dynamic light scattering, powder diffraction, and thermal analysis. Results and Discussion: Depending on the drug's characteristics, the formulation composition, and the study conditions, S-SMEDDS can increase bioavailability by two to ten times. However, for some extremely lipophilic BCS Class II and IV pharmaceuticals, significantly greater benefits (up to ~50-fold) have been documented. Several investigations have demonstrated that S-SMEDDS exhibit better physical and chemical stability than liquid systems under ICH Q1A(R2) accelerated storage conditions due to reduced lipid mobility and a lower risk of phase separation. Applications extend to the treatment of cardiovascular, oncological, and endocrine disorders with improved pharmacodynamic efficacy. The multiple absorption mechanisms in S-SMEDDS include improved solubilization, reduced precipitation, lymphotropic delivery, and inhibition of efflux pumps. They demonstrate higher chemical and physical stability, precise dosing, and better patient adherence when compared to traditional liquid counterparts. Conclusion: S-SMEDDS constitute an established pharmaceutical platform that overcomes the drawbacks associated with liquid lipid drug delivery systems. Their high effectiveness, manufacturability, and compatibility with novel technologies such as three-dimensional printing and artificial intelligence position them to be the foundation for precision oral drug delivery.

Design, Optimization and In-Vitro Characterization of Gamma Oryzanol-Loaded Self-Nanoemulsifying Drug Delivery System (SNEDDS) using Box-Behnken Design

Gamma Oryzanol is a bioactive phytoconstituent with promising antioxidant, anti-inflammatory, and therapeutic properties; however, its clinical application is limited by poor aqueous solubility, slow dissolution rate, and low oral bioavailability. The present study was undertaken to develop and optimize a Self-Nanoemulsifying Drug Delivery System (SNEDDS) for improving the solubility and dissolution behavior of Gamma Oryzanol. A Box-Behnken Design (BBD) integrated with response surface methodology was employed using Design-Expert software to optimize the formulation variables. Three formulation components, namely olive oil (X1), Tween 20 (X2), and PEG 400 (X3), were selected as independent variables, while droplet size (Y1) and turbidity (Y2) were considered as dependent responses. A total of 17 experimental runs were generated and analyzed to establish the relationship between formulation variables and response characteristics. Numerical optimization using the desirability function approach identified an optimized formulation containing olive oil, Tween 20, and PEG 400 in a ratio of 40:40:20. The optimized SNEDDS exhibited a droplet size of 60.44 ± 0.23 nm and a polydispersity index of 0.489, indicating the formation of a uniform nanoemulsion system. Thermodynamic stability studies confirmed the robustness of the formulation under various stress conditions, while dispersibility studies demonstrated rapid self-emulsification with excellent clarity. In vitro dissolution studies revealed a remarkable enhancement in drug release from the optimized SNEDDS, achieving 98.2% cumulative drug release within 60 minutes compared to only 29.1% release from pure Gamma Oryzanol. Furthermore, kinetic modeling indicated that the release profile was best described by the Korsmeyer–Peppas model (R² = 0.9912), suggesting a diffusion-controlled release mechanism. The findings of the present study demonstrate that the developed SNEDDS significantly improved the dissolution characteristics of Gamma Oryzanol and may serve as an effective lipid-based delivery platform for enhancing the oral performance of poorly water-soluble bioactive compounds.

Formulation, Characterization and Evaluation of Polymeric Nanospheres-Based Colon-Targeted Delivery of Oxiconazole Nitrate

Oxiconazole nitrate-loaded nanospheres were successfully developed using the emulsification–solvent evaporation method to enhance the solubility and dissolution of oxiconazole nitrate, a Biopharmaceutics Classification System (BCS) Class II antifungal drug characterized by low aqueous solubility and good membrane permeability. Oxiconazole exerts its antifungal activity by inhibiting lanosterol 14-α-demethylase (CYP51), thereby disrupting ergosterol biosynthesis, compromising fungal cell membrane integrity, and ultimately causing cell lysis. Eudragit RS 100 was employed as the polymeric carrier, with methanol serving as the solvent. The prepared nanospheres were evaluated for particle size, percentage yield, entrapment efficiency, solubility enhancement, Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), zeta potential, and in vitro drug-release characteristics. Among the formulations, batch F5 demonstrated optimum performance, exhibiting an entrapment efficiency and percentage yield of 83.40%, an average particle size of 11.8 nm, and enhanced aqueous solubility in phosphate buffer (pH 7.4). FTIR and DSC analyses confirmed the absence of significant drug–polymer interactions and demonstrated the thermal stability of the formulation. The optimized formulation exhibited a zeta potential of −80.9 mV, indicating excellent colloidal stability. Furthermore, the nanosphere gel (G2) achieved 98.13% drug release within 6 hours, confirming that nanosphere formulation significantly improved the solubility and dissolution behaviour of oxiconazole nitrate.

Thermoresponsive Solid Dispersion to Enhance Dissolution Profile of Atorvastatin Calcium: An Industrially Sustainable Alternative to Conventional Approaches

Background: Poor aqueous solubility of therapeutic molecules remains a limitation in the pharmaceutical development of lipophilic drugs. This requires formulation approaches that provide the desired therapeutic efficacy while being industry-friendly. This study aimed to optimize a thermoresponsive solid dispersion containing atorvastatin calcium to enhance its dissolution performance. Methods: Various nonaqueous solvents were screened to select a thermo-modulating agent. A central composite design was employed to investigate the impact of Pluronic F-68 concentration (5–15% w/w) and atorvastatin calcium concentration (5–10% w/w) on phase transition temperature and phase transition interval. Molecular interactions were assessed by Fourier-transform infrared spectroscopy. The in vitro dissolution of the optimized thermoresponsive solid dispersion was assessed using a USP Apparatus II dissolution test. Results: Propylene glycol was identified as the optimal thermo-modulating agent, forming a rigid carrier through hydrogen bonding with Pluronic F-68. The optimized thermoresponsive solid dispersion consisted of 10.07% w/w Pluronic F-68 and 9.98% w/w atorvastatin calcium. It converted to a solution state at 32 °C. At physiological temperature, the phase transition interval was 111.66 s. Dissolution studies demonstrated that the thermoresponsive solid dispersion enhanced the dissolution profile of atorvastatin calcium within 5 min, 96.6 ± 1.2% compared to 13.8 ± 4.2% for the raw drug. A comparison of process characteristics indicated fewer unit operations and no organic-solvent requirement relative to conventional techniques. Conclusions: This approach enhances dissolution performance and eliminates the need for organic solvents through simple manufacturing processes.