基于醋酸琥珀酸羟丙甲纤维素的无定形固体分散体的热熔挤出：药物物理化学性质的影响。
Hypromellose acetate succinate based amorphous solid dispersions via hot melt extrusion: Effect of drug physicochemical properties.
机构信息
Department of Pharmaceutics and Drug Delivery, The University of Mississippi University, 38677, USA.
Ashland Specialty Ingredients, Wilmington, DE 19808, USA.
出版信息
Carbohydr Polym. 2020 Apr 1;233:115828. doi: 10.1016/j.carbpol.2020.115828. Epub 2020 Jan 10.
Abstract
In this study, the impact of drug and hydroxypropyl methylcellulose acetate succinate (HPMCAS) grades physicochemical properties on extrusion process, dissolution and stability of the hot melt extruded amorphous solid dispersions (ASDs) of nifedipine and efavirenz was investigated. Incorporation of drugs affected the extrusion temperature required for solid dispersion preparation. Differential scanning calorimetry and powder X-ray diffraction studies confirmed the amorphous conversion of the drugs in the prepared formulations. The amorphous nature of ASDs was unchanged after 3 months of stability testing at 40 °C and 75% relative humidity. The dissolution efficiency of the ASDs was dependent on the log P of the drug. The inhibitory effect of HPMCAS on drug precipitation was dependent on the hydrophobic interactions between drug and polymer, polymer grade, and dose of the drug. The dissolution efficiency and dissolution rate of the ASDs were dependent on the log P of the drug and solubility and hydrophilicity of the polymer grade respectively. The inhibitory effect of HPMCAS on drug precipitation was dependent on the hydrophobic interactions between drug and polymer, polymer grade, and the dissolution dose of the drug.
摘要
在这项研究中，考察了药物和羟丙甲纤维素醋酸琥珀酸酯（HPMCAS）等级的物理化学性质对硝苯地平和依非韦伦热熔挤出无定形固体分散体（ASD）挤出过程、溶解和稳定性的影响。药物的掺入影响了用于制备固体分散体所需的挤出温度。差示扫描量热法和粉末 X 射线衍射研究证实了药物在制备配方中的无定形转化。在 40°C 和 75%相对湿度下进行 3 个月的稳定性测试后，ASD 的无定形性质没有变化。ASD 的溶解效率取决于药物的 log P。HPMCAS 对药物沉淀的抑制作用取决于药物和聚合物之间的疏水相互作用、聚合物等级和药物剂量。ASD 的溶解效率和溶解速率取决于药物的 log P 以及聚合物等级的溶解度和亲水性。HPMCAS 对药物沉淀的抑制作用取决于药物和聚合物之间的疏水相互作用、聚合物等级和药物的溶解剂量。
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