普瑞巴林微孔渗透泵片的制备及体外评价
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摘要
制备日服1次的普瑞巴林微孔渗透泵片,并进行处方优化和释药机制考察。采用单因素试验考察了处方和工艺因素对普瑞巴林释放的影响,并对柠檬酸钠、聚乙二醇400的用量和包衣增重3个因素进行3水平的正交试验。结合单因素和正交试验结果得到最优处方和工艺,最终处方为普瑞巴林82. 5 mg,微晶纤维素40%,柠檬酸钠27. 5%,硬脂酸镁0. 5%,黏合剂为5%聚乙烯吡咯烷酮K30溶液,包衣液为醋酸纤维素和60%PEG400致孔剂,包衣增重为3%。释药动力学研究表明,所制备的微孔渗透泵片释放机制以渗透压机制为主,受p H影响较小。对普瑞巴林微孔渗透泵片释放曲线进行拟合,显示12 h内的释放曲线与零级方程拟合的相关性最高,相关系数为0. 991 6,呈零级动力学特征。所得微孔渗透泵片可有效减缓药物释放,可提高药物安全性和减少用药次数,有一定的应用前景。
In this study,pregabalin controlled porosity osmotic pump tablets which are taken once a day were prepared. Single-factor tests were carried out to investigate the influence of excipients and manufacturing process.The formulation was optimized through orthogonal experiment on three levels of three significant factors including the amount of sodium citrate,and polyethylene glycol 400 and coating weight gain. On the basis of the results of the single-factor tests and the orthogonal experiment, optimal formulation and manufacturing process were obtained. The final tablet formulation contained pregabalin( 82. 5 mg),microcrystalline cellulose( 40%),sodium citrate( 27. 5%),magnesium stearate( 0. 5%) and 5% povidone K30 solution as the tablet binder; the coating formulation consisted of cellulose acetrate and 60% of polyethylene glycol 400 as a porogen; the coating weight gain was 3%. In vitro drug release kinetic study suggested that the drug release from controlled porosity osmotic pump tablets was mainly driven by osmotic pressure,which was barely affected by the p H of the release medium.The drug release behavior of the tablets within 12 hours complied with zero-order release rule and the linear correlation coefficient was 0. 991 6. The obtained porosity osmotic pump tablets could effectively slow the drug release rate,reduce concentration fluctuation and improve the safety and convenience for the patients,hence with broad prospects.
In this study,pregabalin controlled porosity osmotic pump tablets which are taken once a day were prepared. Single-factor tests were carried out to investigate the influence of excipients and manufacturing process.The formulation was optimized through orthogonal experiment on three levels of three significant factors including the amount of sodium citrate,and polyethylene glycol 400 and coating weight gain. On the basis of the results of the single-factor tests and the orthogonal experiment, optimal formulation and manufacturing process were obtained. The final tablet formulation contained pregabalin( 82. 5 mg),microcrystalline cellulose( 40%),sodium citrate( 27. 5%),magnesium stearate( 0. 5%) and 5% povidone K30 solution as the tablet binder; the coating formulation consisted of cellulose acetrate and 60% of polyethylene glycol 400 as a porogen; the coating weight gain was 3%. In vitro drug release kinetic study suggested that the drug release from controlled porosity osmotic pump tablets was mainly driven by osmotic pressure,which was barely affected by the p H of the release medium.The drug release behavior of the tablets within 12 hours complied with zero-order release rule and the linear correlation coefficient was 0. 991 6. The obtained porosity osmotic pump tablets could effectively slow the drug release rate,reduce concentration fluctuation and improve the safety and convenience for the patients,hence with broad prospects.
引文
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[7] Li XD,Pan WS,Nie SF,et al. Studies on controlled release effer-vescent osmotic pump tablets from traditional chinese medicinecompound recipe[J]. J Control Release,2004,96(3):359-367.
[8] Adibkia K,Hanaee J,Ghanbarzadeh S,et al. Micro-suspensioncoating method:a new approach in formulation and developmentof controlled porosity osmotic pump systems[J]. Drug Res,2013,64(4):203-207.
[9] Kanagale P,Lohray BB,Misra A,et al. Formulation and optimiza-tion of porous osmotic pump-based controlled release system ofoxybutynin.[J]. AAPS Pharmscitech,2007,8(3):E13-E19.
[10] Li GJ,Wang YJ,Chen HM,et al. Can semipermeable membranescoating materials influence in-vivo performance for paliperidonetri-layer ascending release osmotic pump tablet:in vitro evalua-tion and in vivo pharmacokinetics study[J]. Asian J Pharm Sci,2015,10(2):128-137.
[11] He W,Xue WD,Tang B. Optimization Test Design Method andData Analysis[M]. Chemical Industry Press(化学工业出版社),2012.
[12] Mohanty S,Sahu M,Sirisha A. Osmotic pump a novel approach tocontrol drug delivery[J]. Indo Am J Pharm Res,2014,4(5):2367-2373.
[13] Xu XH,Liao LY,Jiang T. Release mechanism of PNS micro-porous membrane osmotic pump tablets[J]. Chin J Exp TraditMed Form(中国实验方剂学杂志),2012,18(8):12-14.
[2] Stahl SM,Porreca F,Taylor CP,et al. The diverse therapeuticactions of pregabalin:is a single mechanism responsible for severalpharmacological activities[J]? Trends Pharmacol Sci,2013,34(6):332-339.
[3] Tassone DM,Boyce E,Guyer J,et al. Pregabalin:a novel gamma-aminobutyric acid analogue in the treatment of neuropathic pain,partial-onset seizures,and anxiety disorders[J]. Clin Ther,2007,29(1):26-48.
[4] Bockbrader HN,Radulovic LL,Posvar EL,et al. Clinical pharma-cokinetics of pregabalin in healthy volunteers[J]. J Clin Phar-macol,2010,50(8):941-950.
[5] Shokri J,Ahmadi P,Rashidi P,et al. Swellable elementary osmoticpump(SEOP):an effective device for delivery of poorly water-soluble drugs[J]. Eur J Pharm Biopharm,2008,68(2):289-297.
[6] Chen FW,Guo Z,Li HY,et al. Correlation of Fuzilizhong che-mome release from osmotic pump tablets and intrinsic dissolutioncharacteristics from powders[J]. J China Pharm Univ(中国药科大学学报),2012,43(4):329-333.
[7] Li XD,Pan WS,Nie SF,et al. Studies on controlled release effer-vescent osmotic pump tablets from traditional chinese medicinecompound recipe[J]. J Control Release,2004,96(3):359-367.
[8] Adibkia K,Hanaee J,Ghanbarzadeh S,et al. Micro-suspensioncoating method:a new approach in formulation and developmentof controlled porosity osmotic pump systems[J]. Drug Res,2013,64(4):203-207.
[9] Kanagale P,Lohray BB,Misra A,et al. Formulation and optimiza-tion of porous osmotic pump-based controlled release system ofoxybutynin.[J]. AAPS Pharmscitech,2007,8(3):E13-E19.
[10] Li GJ,Wang YJ,Chen HM,et al. Can semipermeable membranescoating materials influence in-vivo performance for paliperidonetri-layer ascending release osmotic pump tablet:in vitro evalua-tion and in vivo pharmacokinetics study[J]. Asian J Pharm Sci,2015,10(2):128-137.
[11] He W,Xue WD,Tang B. Optimization Test Design Method andData Analysis[M]. Chemical Industry Press(化学工业出版社),2012.
[12] Mohanty S,Sahu M,Sirisha A. Osmotic pump a novel approach tocontrol drug delivery[J]. Indo Am J Pharm Res,2014,4(5):2367-2373.
[13] Xu XH,Liao LY,Jiang T. Release mechanism of PNS micro-porous membrane osmotic pump tablets[J]. Chin J Exp TraditMed Form(中国实验方剂学杂志),2012,18(8):12-14.