盐酸倍他司汀渗透泵片的制备及生物等效性

Preparation and bioequivalence study of betahistine hydrochloride osmotic pump tablets

目的以盐酸倍他司汀为模型药物制备渗透泵制剂,并对其与市售普通片剂的生物等效性进行研究。方法应用相似因子法对处方进行优化;采用HPLC法对服药后beagle犬血浆中的药物浓度进行测定。结果通过处方优化,制备了控释时间为12h的渗透泵制剂;自制渗透泵制剂与市售普通片的达峰时间分别为(5.67±0.52)h和(1.33±0.26)h,峰质量浓度分别为(128.73±26.06)μg·L-1和(300.83±58.91)μg·L-1,相对生物利用度为(94.25±6.91)%。结论通过渗透泵技术的使用,能够显著延长盐酸倍他司汀的达峰时间,降低峰浓度,且不改变药物的生物利用度,从而有望降低药物的毒性及不良反应,减少给药频率。

Objective To prepare osmotic pump tablets using betahistine hydrochloride as a model drug and study the bioequivalence between self-made osmotic pump tablets and commercial immediate-release tablets.Methods The formulation was optimized using similarity factor f2,drug concentration in beagle dog plasma was determined by a HPLC method.Results Osmotic pump tablets,which could release betahistine hydrochloride in a controlled manner,was prepared.In vivo study showed that the tmax of self-made osmotic pump and immediate-release tablets were(5.67±0.52) h and(1.33±0.26) h,respectively,the ρmax were(128.73±26.06) μg·h·L-1 and(300.83±58.91) μg·h·L-1,respectively,and the relative bioavailability of self-made osmotic pump tablets versus immediate-release tablets was(94.25±6.91)%.Conclusion By using osmotic pump technology,the tmax of the model drug is prolonged and the ρmax is decreased while the bioavailability is almost unchanged,thus it is possible to decrease the dosing frequency and side-effects of the model drug.