基于药物与羟丙甲纤维素凝胶相互作用的缓释特征参数研究

摘要

目的:通过研究羟丙甲纤维素(HPMC)凝胶对不同药物的阻滞作用,考察HPMC缓释性征参数的适用性,从相互作用的角度阐明亲水凝胶的缓释机理.方法:选择不同性质的5种模型药物(托拉塞米、盐酸洛美利嗪、布洛芬、盐酸氨溴索、盐酸二甲双胍),用三室渗透模型测定药物透过亲水凝胶的速度,取点时间为1,3,7,10和24 h,计算药物的渗透率及阻滞率,利用Material Studio的blend模块计算药物与HPMC的相互作用能,考察试验结果与计算结果的相关性.结果:HPMC的存在对不同的药物影响不同,以3个浓度(5,10,20 mg· mL-1)的阻滞率作为表征HPMC对药物的缓释特征参数可以发现:HPMC对二甲双胍和氨溴索的阻滞能力较弱,对布洛芬和托拉塞米具有较强的吸附作用,对洛美利嗪也有较大的吸收作用,存在饱和现象.理论计算的HPMC与药物相互作用能与24 h阻滞率之间存在明显的相关性.结论:缓释特征参数可以通过高浓度和低浓度的阻滞率,明确药物和辅料的相互作用的方式,帮助药物选择适当的缓释材料,还可以用于保证辅料的本身质量的一致性.%Objective:By studying the blocking effects of hydroxypropyl methyl cellulose (HPMC) gel on the penetration of 5 drugs with different properties,to investigate the applicability of the parameters of sustained release of HPMC,and to clarify the sustained release mechanism of hydrophilic gel from the interaction view.Methods:Five drugs with different properties (torasemide,lomerizine hydrochloride,ibuprofen,ambroxol hydrochloride,metformin hydrochloride) were selected as model drugs.Three-compartment penetrating detection devices were used in experiments.The detection times were 1,3,7,10,24 h.Permeability rate and blocking rate were observed.The interaction energies of drug-HPMC were calculated by blend module of Material Studio's software.Results:The blocking rates form three concentrations (5,10 and 20 mg·mL-1) of HPMC were applied as the parameters to describ the chracteristics of sustained relase.The results showed that the existence of HPMC had different influences on the 5 drugs.HPMC had weak ablity to block the panetration of ambroxol and metformin,and had strong absorption to torasemide and ibuprofen,torasemide.HPMC can block the penatration of lomerizine with saturation effect.The interaction energies form theoretical calculation correlated the experimental blocking rate at 24 hours well.Conclusion:The sustained release paramters baseed on the bloking rate form concentration and low concentration of HPMC are useful to elucidate the interactiom modes between-HPMC and drugs,and to help the selectin of excipients for sustained release formulaton.The parameter can also be used to ensure the quality consistency of excipient itself.