School of Chinese materia medica, Bejing University of Chinese Medicine, Beijing, 100102, People's Republic of China.
AAPS PharmSciTech. 2013 Jun;14(2):629-38. doi: 10.1208/s12249-013-9948-y. Epub 2013 Apr 30.
Ensuring sufficient drug solubility is a crucial problem in pharmaceutical-related research. For water-insoluble drugs, various formulation approaches are employed to enhance the solubility and bioavailability of lead compounds. The goal of this study was to enhance the dissolution and absorption of a new antitumor lead compound, T-OA. Early-stage preparation discovery concept was employed in this study. Based on this concept, a solid dispersion system was chosen as the method of improving drug solubility and bioavailability. Solid dispersions of T-OA in polyvinylpyrrolidone (PVP) K30 were prepared by the solvent evaporation method. Dissolution testing determined that the ideal drug-to-PVP ratio was 1:5. X-ray diffraction, Fourier transform infrared spectroscopy, and differential scanning calorimetry were employed to confirm the formation of solid dispersions. Scanning electron microscopy demonstrated that T-OA was converted into an amorphous form. Both in vitro dissolution testing and the in vivo studies demonstrated that the solubility and bioavailability of T-OA were significantly improved when formulated in a solid dispersion with PVP. The dissolution rate of the T-OA/PVP solid dispersion was greatly enhanced relative to the pure drug, and the relative bioavailability of T-OA solid dispersions was found to be 392.0%, which is 4-fold higher than the pure drug.
确保药物足够的溶解度是药物研究中的一个关键问题。对于水不溶性药物，通常采用各种制剂方法来提高先导化合物的溶解度和生物利用度。本研究旨在提高新型抗肿瘤先导化合物 T-OA 的溶解和吸收。在本研究中采用了早期制剂发现概念。基于该概念，选择固体分散体系统作为提高药物溶解度和生物利用度的方法。采用溶剂蒸发法制备 T-OA 与聚乙烯吡咯烷酮（PVP）K30 的固体分散体。溶出度试验确定理想的药物与 PVP 比例为 1:5。X 射线衍射、傅里叶变换红外光谱和差示扫描量热法用于确证固体分散体的形成。扫描电子显微镜表明 T-OA 转化为无定形形式。体外溶出度试验和体内研究均表明，将 T-OA 制成 PVP 固体分散体后，其溶解度和生物利用度显著提高。T-OA/PVP 固体分散体的溶出速率相对于纯药物大大提高，并且 T-OA 固体分散体的相对生物利用度为 392.0%，是纯药物的 4 倍。
