Sustained-Release Solid Dispersions of Fenofibrate for Simultaneous Enhancement of the Extent and Duration of Drug Exposure. Pharmaceutics BACKGROUND/OBJECTIVES:A sustained-release formulation of fenofibrate while enhancing drug dissolution with minimal food effect is critical for maximizing the therapeutic benefits of fenofibrate. Therefore, this study aimed to develop an effective solid dispersion formulation of fenofibrate for simultaneous enhancement in the extent and duration of drug exposure. METHODS:Fenofibrate-loaded solid dispersions (FNSDs) were prepared using poloxamer 407 and Eudragit RSPO at varied ratios via solvent evaporation. In vitro/in vivo characteristics of FNSDs were examined in comparison with untreated drugs. RESULTS:Based on dissolution profiles of FNSDs in aqueous media, the weight ratio of fenofibrate: poloxamer 407: Eudragit RSPO at 1:1:4 (FNSD2) was selected as the optimal composition for achieving sustained drug release while maximizing the drug dissolution. The enhanced and sustained drug release of FNSD2 was also confirmed in a buffer transition system mimicking the pH change in the gastrointestinal tract. FNSD2 achieved approximately 66% drug release over 12 h, while pure drug exhibited only 12%. Furthermore, FNSD2 maintained similar release rates under fed and fasted conditions, while the entire drug dissolution slightly increased in the fed state. Structural analysis by x-ray diffraction showed that fenofibrate remained crystalline in FNSD2. Pharmacokinetic studies in rats revealed that orally administered FNSD2 significantly improved the extent and duration of systemic drug exposure. Compared to pure drugs, the FNSD2 formulation increased the oral bioavailability of fenofibrate by 22 folds with the delayed T of 4 h in rats. CONCLUSION:FNSD2 formulation is effective in improving the extent and duration of drug exposure simultaneously. 10.3390/pharmaceutics16121617

Twin Screw Melt Granulation of Simvastatin: Drug Solubility and Dissolution Rate Enhancement Using Polymer Blends. Pharmaceutics 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. SIM was processed with various polymeric combinations at a 30% / 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. 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 ( < 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. 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. 10.3390/pharmaceutics16121630