不同来源的HPMC对盐酸二甲双胍缓释片体内外释药特性的影响
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摘要
以市售Glucophage XR为参比制剂,考察了硬度与其相似的进口及国产羟丙甲纤维素(HPMC)制得的盐酸二甲双胍缓释片在pH1.2盐酸与pH 6.8磷酸盐缓冲液中的释放和溶胀性能,采用相似因子法评价自制片与参比制剂体外释放曲线的相似性,并对三者在Beagle犬体内的药动学特征进行研究。动态光散射分析和扫描电镜观察结果表明,进口和国产HPMC的粒度分布基本一致,但进口HPMC粒子表面较粗糙,而国产HPMC的粒子表面较光滑。体外释放研究表明,在2种体外释放介质中,进口及国产HPMC制得的缓释片与Glucophage XR的释放均具有较好的一致性(f_2>70);进口及国产HPMC制得的缓释片在pH 1.2盐酸中的溶胀和溶蚀均比在pH 6.8磷酸盐缓冲液中稍快,与Glucophage XR略有差异;在同一释放介质中,进口及国产HPMC制得的缓释片的溶胀行为略有差异,但溶蚀行为基本一致。Beagle犬体内试验表明,进口及国产HPMC制得的缓释片与Glucophage XR的主要药动学参数均无显著性差异,提示2种自制片与Glucophage XR在Beagle犬体内的药动学行为基本一致。
The aim of this paper was to investigate the effect of different sources of hydroxypropyl methylcellulose(HPMC)on release characteristics of metformin hydrochloride sustained-release tablets in vitro and in vivo.First,the size particle distribution and microstructure of the imported and domestic HPMC were characterized by dymanic light scattering(DLS)and scanning electron microscopy(SEM).The results showed that the imported and domestic HPMC products had a similar particle distribution,while the surface of the imported product was rougher than that of the domestic product.Then,the commercially available Glucophage XR was used as a reference to investigate the release and swelling behaviors of the self-made sustained-release tablets with the same hardness prepared by imported and domestic HPMC in pH 1.2 hydrochloric acid solution and pH 6.8 phosphate buffer.The similarity factor(f_2)values between the release curves of two types of self-made tablets and the reference tablets in two release media were evaluated based on the in vitro release data.The results showed that the release behaviors of two types of self-made tablets had good consistencies with Glucophage XR(f_2>70).The erosion and the swelling behaviors of both self-made tablets in pH 1.2 hydrochloric acid solution were slightly faster than those in pH 6.8 phosphate buffer,and both were slightly different from Glucophage XR.In the same release medium,the swelling behaviors of the two self-made tablets were slightly different,but the erosion behaviors were almost the same.The pharmacokinetic behaviors of the three types of tablets were studied in Beagle dogs.In terms of the main pharmacokinetic parameters in Beagle dogs after a single dose oral administration,there were no significant differences in sustained-release characteristics between both self-made tablets and Glucophage XR.In conclusion,there were no significant effects of HPMC from different sources on the release of metformin hydrochloride sustained-release tablets in vitro and in vivo.
The aim of this paper was to investigate the effect of different sources of hydroxypropyl methylcellulose(HPMC)on release characteristics of metformin hydrochloride sustained-release tablets in vitro and in vivo.First,the size particle distribution and microstructure of the imported and domestic HPMC were characterized by dymanic light scattering(DLS)and scanning electron microscopy(SEM).The results showed that the imported and domestic HPMC products had a similar particle distribution,while the surface of the imported product was rougher than that of the domestic product.Then,the commercially available Glucophage XR was used as a reference to investigate the release and swelling behaviors of the self-made sustained-release tablets with the same hardness prepared by imported and domestic HPMC in pH 1.2 hydrochloric acid solution and pH 6.8 phosphate buffer.The similarity factor(f_2)values between the release curves of two types of self-made tablets and the reference tablets in two release media were evaluated based on the in vitro release data.The results showed that the release behaviors of two types of self-made tablets had good consistencies with Glucophage XR(f_2>70).The erosion and the swelling behaviors of both self-made tablets in pH 1.2 hydrochloric acid solution were slightly faster than those in pH 6.8 phosphate buffer,and both were slightly different from Glucophage XR.In the same release medium,the swelling behaviors of the two self-made tablets were slightly different,but the erosion behaviors were almost the same.The pharmacokinetic behaviors of the three types of tablets were studied in Beagle dogs.In terms of the main pharmacokinetic parameters in Beagle dogs after a single dose oral administration,there were no significant differences in sustained-release characteristics between both self-made tablets and Glucophage XR.In conclusion,there were no significant effects of HPMC from different sources on the release of metformin hydrochloride sustained-release tablets in vitro and in vivo.
引文
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[7]BONFERONI MC,ROSSI S,FERRARI F,et al.A study of three hydroxypropylmethyl cellulose substitution types:Effect of particle size and shape on hydrophilic matrix performances[J].S.T.P.Pharma Pratiques,1999,6(4):277-284.
[8]TIMMINS P,DENNIS A B,VYAS K A.Biphasic controlled release delivery system for high solubility pharmaceuticals and method:WO,1999/047128[P].1999-09-23.
[2]褚杰,刘秀萍,臧恒昌.口服缓控释制剂的研究概述[J].药物生物技术,2015,22(3):275-278.
[3]胡雄伟,张倩,宋洪涛.口服缓控释骨架片给药系统的研究进展[J].中国药房,2010,21(17):1619-4622.
[4]ZHOU D,LAW D,REYNOLDS J,et al.Understanding and managing the impact of HPMC variability on drug release from controlled release formulations[J].J Pharm Sci,2014,103(6):1664-1672.
[5]孔灵敏,秦少容.国产与进口羟丙基甲基纤维素用于硝苯地平缓释片时的比较[J].中国药业,2011,20(1):42-43.
[6]周元香,朱永波,国产与进口羟丙甲纤维素作为缓释骨架材料的比较研究[J].中国药业,2009,18(11):36-37.
[7]BONFERONI MC,ROSSI S,FERRARI F,et al.A study of three hydroxypropylmethyl cellulose substitution types:Effect of particle size and shape on hydrophilic matrix performances[J].S.T.P.Pharma Pratiques,1999,6(4):277-284.
[8]TIMMINS P,DENNIS A B,VYAS K A.Biphasic controlled release delivery system for high solubility pharmaceuticals and method:WO,1999/047128[P].1999-09-23.