罗红霉素在胃肠道介质中溶解度、油水分配系数、稳定性及原研片溶出行为研究

目的: 测定罗红霉素在胃肠道介质中溶解度、油水分配系数及稳定性,并研究原研药片在4种溶出介质中的溶出规律,为罗红霉素固体制剂的剂型、处方和溶出度检查方法的设计和改进提供科学依据。 方法: 采用HPLC法测定,油水分配系数以正辛醇-水为模拟系统,溶出度检查采用转篮法、转速为100 r·min^-1。 结果: 罗红霉素在酸性介质中极不稳定,在胃肠道近中性pH范围,罗红霉素的溶解度较低、油水分配系数较大,属于BCS分类系统 Ⅱ 类。 原研片在酸性介质中溶出较少,15 min溶出量仅为14%,而在pH 5.5醋酸钠缓冲液介质中快速溶出,15 min溶出量在85%以上。 结论: 通过对罗红霉素理化性质和原研药片溶出规律的研究,认为其制剂设计为类似于肠溶制剂更为合理,应当在酸性介质中溶出少、在近中性介质中快速溶出。

Objective: To determine the solubility,oil/water partition coefficient and stability of roxithromycin in gastrointestinal medium and to study the dissolution behavior of original tablet in four dissolution media,so as to provide a scientific basis for the designing and improvement of roxithromycin solid preparations,prescriptions and dissolution test methods. Methods: A high performance liquid chromatography method was used to determine roxithromycin contents.The oil/water partition coefficient simulation system was noctanol-water.The dissolution Apparatus 1 was used with 100 r·min^-1. Results: Roxithromycin was extremely unstable in acidic medium and had a low solubility and a high partition coefficient in the gastrointestinal tract in the neutral pH range,so it belonged to BCS II.The original tablet showed low dissolution in acidic medium,and the dissolution was only 14% in 15 minutes,while the dissolution was fast in sodium acetate buffer medium at pH 5.5,where the dissolution in 15 minutes was above 85%. Conclusion: Based on the study of physical and chemical properties and dissolution behavior of original tablet,the dosage design is more reasonable if the formulation design is similar to the enteric preparation,which has low dissolution in acidic medium and rapid dissolution in a neutral medium.