Nandi Uttom, Ajiboye Adejumoke Lara, Patel Preksha, Douroumis Dennis, Trivedi Vivek
Medway School of Pharmacy, University of Kent, Central Avenue, Chatham Maritime, Chatham, Kent ME4 4TB, UK.
School of Science, University of Greenwich, Central Avenue, Chatham Maritime, Kent ME4 4TB, UK.
Pharmaceuticals (Basel). 2021 Aug 25;14(9):846. doi: 10.3390/ph14090846.
The study was designed to investigate the feasibility of supercritical carbon dioxide (scCO) 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 scCO 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.
本研究旨在探究在低于聚合物玻璃化转变温度的条件下，采用超临界二氧化碳（scCO）处理法制备辛伐他汀（SIM）在固体分散体（SDs）中的可行性。在SDs实验设计中，SIM含量保持在10%、20%和30%，以研究药物-聚合物比例对成功制备SDs的影响。使用X射线衍射（XRD）、差示扫描量热法（DSC）、衰减全反射-傅里叶变换红外光谱（ATR-FTIR）、扫描电子显微镜（SEM）和溶出度研究对SIM-SOL制剂、物理混合物（PMs）和SDs进行了评估。发现scCO处理条件和药物-聚合物比例会影响制剂中药物的物理化学性质。SIM是一种高度结晶的药物；然而，通过SEM、DSC和XRD进行的物理化学表征表明，SDs中存在无定形的SIM。SIM-SOL SDs显示出提高的药物溶出速率，在45分钟内释放率达100%。此外，与PMs相比，SDs的药物溶出更快且更高。总之，本研究表明，使用无溶剂超临界流体工艺可成功制备SIM-SOL分散体，以提高药物的溶出速率。
