响应面法制备格列美脲环糊精包合物
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摘要
目的制备格列美脲-羟丙基-β-环糊精包合物并对其处方进行优化。方法通过Box-Behnken响应面法,在单因素实验的基础上以稀释剂比例、黏合剂浓度和崩解剂比例为考察因素,以环糊精包合物片的释放度为评价指标对处方进行优化;用红外光谱法表征制备的包合物,并对制得的格列美脲片进行质量评价,拟合体外释放曲线。结果响应面法优化得到最佳处方为:稀释剂-乳糖和MCC的比例为7.37:1,黏合剂-PVP的浓度为6%,崩解剂-CMS-NA的比例为6.45%;按此条件进行3组平行实验,所得验证值为88.13%,回归方程所得理论预测值为88.69%,两者相对误差为0.64%。红外光谱显示形成了格列美脲包合物;其溶解度为68.53μg/mL,较格列美脲原料药提高了50.39倍。结论体外释放实验表明HP-β-CD格列美脲片相比普通格列美脲片的释放度有显著提高,响应面法优化格列美脲包合物处方可行,为格列美脲片进一步开发奠定了良好的理论基础。
Objective To prepare the inclusion complex of glimepiride with hydroxypropyl-β-cyclodextrin(HP-β-CD) and to optimize its formulation. Methods The prescription was optimized by the Box-Behnken response surface methodology(RSM) with the diluent ratio, adhesive concentration, and disintegrant ratio as the investigation factors and the release rate of tablets as the evaluation index based on the single factor experiment. The prepared inclusion complex was characterized by infrared spectroscopy, and the quality of the tablets was evaluated and the in vitro release curve was fitted. Results The optimal formulation was as followed: the ratio of diluent-lactose to MCC was 7.37:1, the concentration of binder-PVP was 6%, and the ratio of disintegrant-CMS-NA was 6.45%. The conditions were carried out in three sets of parallel experiments, and the obtained verification value was 88.13%. The theoretical prediction value of the regression equation was 88.69% and the relative error was 0.64%. Infrared spectroscopy showed the formation of glimepiride clathrate; its solubility was 68.53μg/mL, which was 50.39 times higher than that of glimepiride. Conclusions The in vitro release test showed that the release rate of HP-β-CD glimepiride tablets was significantly higher than that of common glimepiride tablets. It is feasible to optimize the prescription of glimepiride inclusion complex using RSM, which offers a good theoretical support for the further development of glimepiride tablets.
Objective To prepare the inclusion complex of glimepiride with hydroxypropyl-β-cyclodextrin(HP-β-CD) and to optimize its formulation. Methods The prescription was optimized by the Box-Behnken response surface methodology(RSM) with the diluent ratio, adhesive concentration, and disintegrant ratio as the investigation factors and the release rate of tablets as the evaluation index based on the single factor experiment. The prepared inclusion complex was characterized by infrared spectroscopy, and the quality of the tablets was evaluated and the in vitro release curve was fitted. Results The optimal formulation was as followed: the ratio of diluent-lactose to MCC was 7.37:1, the concentration of binder-PVP was 6%, and the ratio of disintegrant-CMS-NA was 6.45%. The conditions were carried out in three sets of parallel experiments, and the obtained verification value was 88.13%. The theoretical prediction value of the regression equation was 88.69% and the relative error was 0.64%. Infrared spectroscopy showed the formation of glimepiride clathrate; its solubility was 68.53μg/mL, which was 50.39 times higher than that of glimepiride. Conclusions The in vitro release test showed that the release rate of HP-β-CD glimepiride tablets was significantly higher than that of common glimepiride tablets. It is feasible to optimize the prescription of glimepiride inclusion complex using RSM, which offers a good theoretical support for the further development of glimepiride tablets.
引文
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[10]王天怡,李文静,王岩,等.伏立康唑/羟丙基倍他环糊精包合物的制备及性质考察[J].沈阳药科大学学报,2015,32(5):331-335,342.
[11]国家药典委员会.中华人民共和国药典[S].(2015年版四部).北京:化学工业出版社,2015:4,120-125.
[2]Sawa T,Takata N,Tanaka M.Efficacy of glimepiride in Japanese Type 2 diabetic subjects[J].Diabetes Res Clin Pract,2005,68(3):250-257.
[3]方志华,梁君伟,吕喜英.格列美脲下调miRNA-214表达抑制人乳腺癌细胞MCF-7增殖作用的研究[J].中国药业,2018,27(18):14-17.
[4]P?duraru O M,Bos?nceanu A,?antaru G,et al.Effect of hydroxypropyl-β-cyclodextrin on the solubility of an antiarrhythmic agent[J].Ind Eng Chem Res,2013,52(5):2174-2181.
[5]Ammar H O,Salama H A,Ghorab M,et al.Formulation and biological evaluation of glimepiride-cyclodextrin-polymer systems[J].Int J Pharm,2006,309(1):129-138.
[6]Si Z,Zuo P,Zuo Y,et al.A rapid hydrophilic interaction liquid chromatographic determination of glimepiride in pharmaceutical formulations[J].Saudi Pharm J,2017,25(6):852-856.
[7]Dash R N,Mohammed H,Humaira T.An integrated taguchi and response surface methodological approach for the optimization of an HPLC method to determine glimepiride in a supersaturatable self-nanoemulsifying formulation[J].Saudi Pharm J,2016,24(1):92-103.
[8]李海鹰,杨文智,马丽兰,等.难溶药物格列美脲的片剂处方设计及溶出评价[J].河北大学学报(自然科学版),2014,34(5):491-496.
[9]刘龙孝,朱素燕.羟丙基-β-环糊精包合对盐酸哌唑嗪的增溶作用研究[J].中国药学杂志,2006,41(2):122-125.
[10]王天怡,李文静,王岩,等.伏立康唑/羟丙基倍他环糊精包合物的制备及性质考察[J].沈阳药科大学学报,2015,32(5):331-335,342.
[11]国家药典委员会.中华人民共和国药典[S].(2015年版四部).北京:化学工业出版社,2015:4,120-125.