盐酸吡格列酮/盐酸二甲双胍缓释片的体内外评价

In vitro and in vivo evaluation of pioglitazone hydrochloride/metformin hydrochloride sustained-release tablets

目的:研制盐酸吡格列酮(PH)/盐酸二甲双胍(MH)缓释片,并进行体内外评价。方法:以HPMC K100M为片芯缓释材料,以EudragitNE 30D进行包衣,采用亲水骨架结合缓释膜包衣技术,得到MH缓释部分;采用包衣上药技术制备吡格列酮速释部分。比较不同介质下(pH 2.0盐酸、pH 4.5醋酸盐缓冲液、水、pH 6.8磷酸盐缓冲液)自制片与参比制剂两组分的释放/溶出行为,测定Beagle犬口服单剂量后血浆中的药物浓度,推算药动学参数。结果:MH在不同介质中的释放曲线均与参比制剂相似,体外释放行为符合Higuchi方程。PH在pH 2.0盐酸中溶出曲线相似,在其余3种介质中均略高于参比制剂。犬体内药动学研究表明,自制片与参比制剂相比,MH的相对生物利用度为(93.38±10.72)%;PH的相对生物利用度为(100.72±19.28)%。结论:自研片与参比制剂生物等效,MH体外释放和体内吸收有良好的相关性。

Objective：To prepare pioglitazone hydrochloride（PH）/metformin hydrochloride（MH） sustained-release tablets,and evaluate their release behaviors in vitro and in vivo.Methods：The MH sustained-release part was prepared by hydrophilic matrix combined with sustained release film coating technology.The HPMC K100M and EudragitNE 30D were used as hydrophilic matrix and film coating.The PH immediate-release part was prepared by coating technology.The release/dissolution behaviors were evaluated in different dissolution media[hydrochloric acid（pH 2.0）,acetic acid buffer solution（pH 4.5）,purified water,and phosphate buffer solution（pH 6 8） ].The in vivo pharmacokinetics of the tablets was investigated in Beagle dogs.Results：The release characteristics of MH in different media were similar with that of reference tablets.Higuchi model was optimal for the description of drug release profile.The dissolution characteristic of PH in pH 2.0 was similar with reference tablets,but higher than reference tablets in other PH dissolution media.The results of pharmacokinetics in Beagle dogs showed that relative bioavailability of MH and PH was（93.38 ± 10.72） % and（100.72 ± 19.28） %,respectively.Conclusion：The obtained tablets were bioequivalent to reference tablets.The MH release from sustained-release part showed good in vitro-in vivo correlations.