The object of this study was to prepare binary and ternary solid dispersions of atorvastatin (ATR) by the melting method using PEGs and poloxamer 188 (P188) as the carriers, singly and in combination with each other. Dissolution behavior, solubility studies, X-ray diffractometry, differential scanning calorimetry, and Fourier transform infrared spectroscopy were studied. Furthermore, antihyperlipidemic activities of formulations were compared to each other by serum lipid analyses in hyperlipidemic rats. Based on the results, the highest dissolution efficiency () was obtained by binary systems consisted of ATR and P188. Also, no additional improvement was observed in dissolution properties of ternary solid dispersion formulations. Solubility studies showed enhancement of ATR phase solubility in water and a buffer solution containing P188 or PEG 10000. Furthermore, saturated solubility of ATR in the buffer solution improved more than twofold in the optimized ternary dispersion system. No crystalline changes occurred in PEG-based formulations; meanwhile, partial amorphization happened in the ATR-P188 combination. Finally, the in vivo study in hyperlipidemic rats exhibited a rapid decrease in the lipid profile of all formulations compared to ATR (after 7 days). Moreover, reduction of serum triglycerides and total cholesterol on the 14th day in the ATR group ( value < 0.01) was less than solid dispersion or physical mixing preparations ( value < 0.001). These findings proved the appropriate influence of using PEG and P188 in solid dispersion systems for the improvement of the therapeutic efficiency of ATR.

中文翻译：

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二元和三元阿托伐他汀固体分散体的开发：体外和体内研究


本研究的目的是以聚乙二醇和泊洛沙姆188（P188）为载体，单独或联合熔融法制备阿托伐他汀（ATR）二元和三元固体分散体。研究了溶解行为、溶解度研究、X 射线衍射法、差示扫描量热法和傅里叶变换红外光谱法。此外，通过高脂血症大鼠的血清脂质分析比较了制剂的抗高脂血症活性。根据结果​​，最高的溶出效率（ ）是通过ATR和P188组成的二元系统获得的。此外，三元固体分散体制剂的溶出性能没有观察到额外的改善。溶解度研究表明，ATR 相在水和含有 P188 或 PEG 10000 的缓冲溶液中的溶解度有所增强。此外，在优化的三元分散体系中，ATR 在缓冲溶液中的饱和溶解度提高了两倍以上。基于 PEG 的配方没有发生结晶变化；同时，ATR-P188组合发生部分非晶化。最后，高脂血症大鼠的体内研究显示，与 ATR 相比（7 天后），所有制剂的脂质谱均迅速下降。此外，ATR组第14天血清甘油三酯和总胆固醇的降低（值<0.01）小于固体分散体或物理混合制剂（值<0.001）。 这些结果证明了在固体分散体系中使用PEG和P188对于提高ATR的治疗效率具有适当的影响。