Preparation of Solid Dispersions of Simvastatin and Soluplus Using a Single-Step Organic Solvent-Free Supercritical Fluid Process for the Drug Solubility and Dissolution Rate Enhancement

• Main Authors: Uttom Nandi (Author), Adejumoke Lara Ajiboye (Author), Preksha Patel (Author), Dennis Douroumis (Author), Vivek Trivedi (Author)
• Format: Book
• Published: MDPI AG, 2021-08-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.3390/ph14090846; 1424-8247
• Keywords: simvastatin; supercritical carbon dioxide; soluplus; drug dissolution; Medicine; R; Pharmacy and materia medica; RS1-441
• Source: Pharmaceuticals, Vol 14, Iss 9, p 846 (2021)

The study was designed to investigate the feasibility of supercritical carbon dioxide (scCO₂) processing for the preparation of simvastatin (SIM) solid dispersions (SDs) in Soluplus^® (SOL) at temperatures below polymer's glass transition. The SIM content in the SDs experimental design was kept at 10, 20 and 30% to study the effect of the drug-polymer ratio on the successful preparation of SDs. The SIM-SOL formulations, physical mixtures (PMs) and SDs were evaluated using X-ray diffraction (XRD), differential scanning calorimetry (DSC), attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), scanning electron microscopy (SEM), and dissolution studies. The scCO₂ processing conditions and drug-polymer ratio were found to influence the physicochemical properties of the drug in formulated SDs. SIM is a highly crystalline drug; however, physicochemical characterisation carried out by SEM, DSC, and XRD demonstrated the presence of SIM in amorphous nature within the SDs. The SIM-SOL SDs showed enhanced drug dissolution rates, with 100% being released within 45 min. Moreover, the drug dissolution from SDs was faster and higher in comparison to PMs. In conclusion, this study shows that SIM-SOL dispersions can be successfully prepared using a solvent-free supercritical fluid process to enhance dissolution rate of the drug.