Patel Jayvadan K, Sutariya Vijaykumar B
Department of Pharmceutics, Nootan Pharmacy College , Visnagar , India and.
J Microencapsul. 2015;32(2):193-200. doi: 10.3109/02652048.2014.995726. Epub 2014 Dec 23.
Micronisation of simvastatin dissolved in acetone, dimethyl sulfoxide and ethanol with supercritical carbon dioxide as antisolvent was successfully performed using a supercritical antisolvent technique. The effect of a few process parameters such as precipitation temperature, the pressure and solute concentration in the liquid solution has been studied to evaluate their influence on morphology and size of particles. The micronised simvastatin were evaluated for drug content, particle size analysis and in vitro dissolution profiles. Fourier transform infrared spectroscopy, differential scanning calorimetry and PXRD patterns was used to study the possible changes after micronisation of simvastatin. The dissolution rate was increased after micronised compared with pure simvastatin in distilled water, pH 1.2 buffer and pH 7.0 buffer. In vivo performance of the optimised formulation was evaluated in rats using pharmacodynamic marker parameters like serum total cholesterol (CH) and triglycerides (TG) for 21 days. Pharmacodynamic studies of micronised simvastatin revealed improved reduction in CH and TG values as compared with pure simvastatin indicating improved bioavailability. In vivo pharmacokinetics in rats showed an increase in bioavailability of micronised simvastatin (3.14 times) compared with plain simvastatin.
采用超临界抗溶剂技术，成功地以超临界二氧化碳作为抗溶剂，对溶解在丙酮、二甲基亚砜和乙醇中的辛伐他汀进行了微粉化处理。研究了一些工艺参数（如沉淀温度、压力和液相中的溶质浓度）对颗粒形态和尺寸的影响。对微粉化的辛伐他汀进行了药物含量、粒度分析和体外溶出度曲线评估。采用傅里叶变换红外光谱、差示扫描量热法和粉末X射线衍射图谱研究辛伐他汀微粉化后可能发生的变化。与纯辛伐他汀相比，微粉化后的辛伐他汀在蒸馏水、pH 1.2缓冲液和pH 7.0缓冲液中的溶出速率有所提高。使用血清总胆固醇（CH）和甘油三酯（TG）等药效学标记参数，在大鼠体内对优化后的制剂进行了21天的药效学性能评估。微粉化辛伐他汀的药效学研究表明，与纯辛伐他汀相比，CH和TG值的降低更为显著，表明生物利用度有所提高。大鼠体内药代动力学研究表明，微粉化辛伐他汀的生物利用度比普通辛伐他汀提高了3.14倍。
