Department of Pharmaceutics, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
Targeted Drug Delivery Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
AAPS PharmSciTech. 2024 Jul 3;25(6):154. doi: 10.1208/s12249-024-02863-1.
Berberine is used in the treatment of metabolic syndrome and its low solubility and very poor oral bioavailability of berberine was one of the primary hurdles for its market approval. This study aimed to improve the solubility and bioavailability of berberine by preparing pellet formulations containing drug-excipient complex (obtained by solid dispersion). Berberine-excipient solid dispersion complexes were obtained with different ratios by the solvent evaporation method. The maximum saturation solubility test was performed as a key factor for choosing the optimal complex for the drug-excipient. The properties of these complexes were investigated by FTIR, DSC, XRD and dissolution tests. The obtained pellets were evaluated and compared in terms of pelletization efficiency, particle size, mechanical strength, sphericity and drug release profile in simulated media of gastric and intestine. Solid-state analysis showed complex formation between the drug and excipients used in solid dispersion. The optimal berberine-phospholipid complex showed a 2-fold increase and the optimal berberine-gelucire and berberine-citric acid complexes showed more than a 3-fold increase in the solubility of berberine compared to pure berberine powder. The evaluation of pellets from each of the optimal complexes showed that the rate and amount of drug released from all pellet formulations in the simulated gastric medium were significantly lower than in the intestine medium. The results of this study showed that the use of berberine-citric acid or berberine-gelucire complex could be considered a promising technique to increase the saturation solubility and improve the release characteristics of berberine from the pellet formulation.
小檗碱用于治疗代谢综合征，其低溶解度和极差的口服生物利用度是其获得市场批准的主要障碍之一。本研究旨在通过制备含有药物-赋形剂复合物（通过固体分散体获得）的颗粒制剂来提高小檗碱的溶解度和生物利用度。通过溶剂蒸发法以不同比例获得小檗碱-赋形剂固体分散体复合物。最大饱和溶解度测试是选择药物-赋形剂最佳复合物的关键因素。通过傅里叶变换红外光谱（FTIR）、差示扫描量热法（DSC）、X 射线衍射（XRD）和溶解试验研究了这些复合物的性质。对获得的颗粒进行了评估，并在模拟胃和肠介质中的颗粒化效率、粒径、机械强度、球形度和药物释放特性方面进行了比较。固态分析表明药物与固体分散体中使用的赋形剂之间存在复合物形成。与纯小檗碱粉末相比，最佳小檗碱-磷脂复合物使小檗碱的溶解度增加了 2 倍，最佳小檗碱-吉拉西醇和小檗碱-柠檬酸复合物使小檗碱的溶解度增加了 3 倍以上。对每个最佳复合物的颗粒进行评估的结果表明，所有颗粒制剂在模拟胃介质中的药物释放速率和释放量均明显低于在肠介质中的释放速率和释放量。本研究结果表明，使用小檗碱-柠檬酸或小檗碱-吉拉西醇复合物可以被认为是一种提高小檗碱饱和溶解度和改善其从颗粒制剂中释放特性的有前途的技术。
