Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; School of Pharmacy, University of Chinese Academy of Sciences, Beijing 100049, China.
Novo Nordisk Research Centre China, Department of Pharmacology and Histopathology, Discovery Biology China, Beijing 102206, China.
J Pharm Sci. 2019 Jun;108(6):2128-2135. doi: 10.1016/j.xphs.2019.01.025. Epub 2019 Feb 2.
Absorption enhancers are often a major component of solid oral peptide formulations as compared to the active pharmaceutical ingredient and excipients. This commonly results in poor tabletability that is hard to mitigate in direct compaction by addition of small amounts of excipients. To improve the tabletability of bulky absorption enhancers, the model absorption enhancers, sodium cholate and deoxycholic acid, were co-spray-dried with hydroxypropyl methylcellulose E5, where the percentage of absorption enhancers was not lower than 90% (w/w). The physicochemical properties of the resulting powders were assessed by laser diffraction, scanning electron microscopy, X-ray powder diffraction, thermogravimetric analysis, and differential scanning calorimetry. The powders were compressed into tablets, and the tabletability was evaluated. Co-spray drying with 10% of hydroxypropyl methylcellulose significantly improved the tabletability of the both absorption enhancers. Moreover, it was demonstrated that small particle size and amorphous state rather than high moisture content contributed to the improved tabletability of the spray-dried powders. The study suggests that spray drying technology can be promising to overcome the poor tabletability of oral peptide formulation consisting of large amounts of absorption enhancers.
吸收促进剂通常是固体口服肽制剂的主要成分，与活性药物成分和赋形剂相比。这通常导致片剂成型性差，通过添加少量赋形剂很难缓解直接压缩。为了提高体积大的吸收促进剂的可压性，将模型吸收促进剂胆酸钠和脱氧胆酸与羟丙基甲基纤维素 E5 共喷雾干燥，其中吸收促进剂的百分比不低于 90%（w/w）。通过激光衍射、扫描电子显微镜、X 射线粉末衍射、热重分析和差示扫描量热法评估所得粉末的物理化学性质。将粉末压缩成片剂，并评估片剂成型性。用 10%的羟丙基甲基纤维素共喷雾干燥显著改善了两种吸收促进剂的可压性。此外，研究表明，小粒径和无定形状态而不是高水分含量有助于改善喷雾干燥粉末的可压性。该研究表明，喷雾干燥技术有望克服由大量吸收促进剂组成的口服肽制剂的可压性差的问题。
