羟丙基甲基纤维素骨架片中难溶性药物释放模型的研究

目的:研究羟丙基甲基纤维素(HPMC)骨架片中难溶性药物释放的机理,建立数学模型,用于预测药物释放.方法:以卡马西平(CBM)为难溶性模型药物,测定药物释放量及HPMC的溶蚀量与时间的关系,通过计算处方组分的等价重均分子量(Meq),导出定量化数学模型.结果:CBM释放符合HPMC骨架溶蚀控制机理.用HPMC15M系列实验结果导出HPMC的溶蚀数学模型:MP(t)/MP(∞)=-[0.8095ln(t) 1.2775]Meq(-0.0622t-0.305),导出CBM从HPMC骨架中溶出的数学模型:Md(t)/Md(∞)=-[0.1891t-0.1294]Meq-0.9326.用以上两个数学模型分别预测HPMC K4M组分处方中HPMC溶蚀与CBM释放,理论值与实验实测值有较好的吻合度.结论:该种数学模型适用于HPMC中以骨架溶蚀机理为主的难溶性药物的释放行为的定量描述.

Investigation on release model of insoluble drug in hydroxypropyl methycellulose matrix tablets

OBJECTIVE: To investigate the release model of insoluble drug carbamazepine (CBM) based on HPMC matrix tablets. METHODS: CBM release profile from matrices and HPMC erosion rate were determined. RESULT: The mathematical model by matrix erosion rate and drug release from HPMC K15M were established for the fractional HPMC and CBM released as M(P(t))/M(P(infinity))=-[0.8095ln((t))+1.2775]Meq((-0.0622t-0.305)) and M(d(t))/M(d(infinity))=-[0.1891t-0.1294]Meq(-0.9326). In comparison with the data of HPMC K4M matrix erosion and CBM release from HPMC K4M matrices, theoretical value agreed well with experimental data. CONCLUSION: The two mathematical models can be satisfactorily applied to insoluble drug release, which is governed by matrix erosion.