盐酸地芬尼多双层渗透泵片的制备及处方优化
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摘要
目的:制备盐酸地芬尼多双层渗透泵片,并对该制剂的体外释药行为进行考察。方法:测定各处方的累积释放度,以累积释放量和f_2相似因子作为评价标准,采用单因素试验筛选盐酸地芬尼多双层渗透泵片的片芯处方和包衣工艺。结果:盐酸地芬尼多双层渗透泵片的释药行为受含药层聚氧乙烯(PEO)含量、氯化钠含量及包衣增重等因素影响。片芯优化处方含药层氯化钠为10 mg,PEO-N10为15 mg;助推层PEO-WSR303为60 mg,氯化钠为20 mg;包衣液优化处方PEG4000为1. 25 g·L~(-1);包衣增重为片芯重量的7%。优化处方在2～12 h内零级特征明显,释药方程为:Q=6. 308t-2. 503 7(r=0. 995 8)。结论:研制的盐酸地芬尼多双层渗透泵片制备工艺稳定,体外释药特征符合零级模型。
Objective: To prepare diphenidol hydrochloride push-pull osmotic pump tablets and in-vestigate the influence of different factors on in-vitro drug release. Methods: The cumulative release of different formulas was detected. Using the cumulative release and similarity factor f_2 as the evaluation criterion,single factor experiment was applied to screen the core formula and coating process.Results: The drug release behavior was affected by the content of PEO in the drug containing layer,the content of NaCl and the weight gain of the coating layer. After the formula was optimized,the NaCl content in the drug containing layer was 10 mg,the PEO-N10 content was 15 mg. In the push layer,the content of PEO-WSR303 was 60 mg,that of NaCl was 20 mg. The optimized coating liquid formula contained 1. 25 g·L~(-1) PEG4000 and the coating weight gain was 7% of the core. The optimized formula fitted a zero-order equation within 2~(-1)2 h with the drug release equation of Q = 6. 308 t-2. 5037( r = 0. 995 8). Conclusion: The preparation technology of diphenidol hydrochloride push-pull osmotic pump tablets is stable,and the in-vitro drug release fits zero-order model.
Objective: To prepare diphenidol hydrochloride push-pull osmotic pump tablets and in-vestigate the influence of different factors on in-vitro drug release. Methods: The cumulative release of different formulas was detected. Using the cumulative release and similarity factor f_2 as the evaluation criterion,single factor experiment was applied to screen the core formula and coating process.Results: The drug release behavior was affected by the content of PEO in the drug containing layer,the content of NaCl and the weight gain of the coating layer. After the formula was optimized,the NaCl content in the drug containing layer was 10 mg,the PEO-N10 content was 15 mg. In the push layer,the content of PEO-WSR303 was 60 mg,that of NaCl was 20 mg. The optimized coating liquid formula contained 1. 25 g·L~(-1) PEG4000 and the coating weight gain was 7% of the core. The optimized formula fitted a zero-order equation within 2~(-1)2 h with the drug release equation of Q = 6. 308 t-2. 5037( r = 0. 995 8). Conclusion: The preparation technology of diphenidol hydrochloride push-pull osmotic pump tablets is stable,and the in-vitro drug release fits zero-order model.
引文
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11 中国药典[S]. 2015年版.四部. 121-124
12 张冠男,白靖,曹德英.尼莫地平双层渗透泵片的制备及其体外释放度考察[J].中国药房,2012,23(29):2740-2743
13 李佳,郭玲,宋旭,等.硝苯地平双层渗透泵控释片的制备[J].华西药学杂志,2015,30(01):18-21
2 Zhang L,Ma J,Li S,et al. Fatal diphenidol poisoning:a case report and a retrospective study of 16 cases[J]. Forensic Sci Med Pathol,2015,11(4):570-576
3 Murakami K,Inoue N,Fuchikami C,et al. Blockade of voltage-gated calcium channel Cav1. 2 and alpha1-adrenoceptors increases vertebral artery blood flow induced by the antivertigo agent difenidol[J]. Eur J Pharmacol,2012,689(1-3):165-171
4 Leung YM,Wu BT,Chen YC,et al. Diphenidol inhibited sodium currents and produced spinal anesthesia[J]. Neuropharmacology,2010,58(7):1147-1152
5 Hernandez J,Marcelin-Jimenez G,Rivera L,et al. Development of an HPLC method for determination of diphenidol in plasma and its application in an oral multi-dose bioequivalence study in a healthy female Mexican population[J]. J Pharm Biomed Anal,2005,38(4):746-750
6 马磊.渗透泵给药系统的研究进展[J].中国药科大学学报,2014,45(06):726-730
7 Wu C,Zhao Z,Zhao Y,et al. Preparation of a push-pull osmotic pump of felodipine solubilized by mesoporous silica nanoparticles with a core-shell structure[J]. Int J Pharm,2014,475(1-2):298-305
8 Xu H,Li Z,Pan H,et al. A novel bi-layer ascending release osmotic pump tablet:in vitro investigation and in vivo investigation in pharmacokinetic study and IVIVC evaluation[J]. Int J Pharm,2013,458(1):181-187
9 朱兰琼.盐酸地芬尼多渗透泵控释片的研究[D].广州:南方医科大学硕士学位论文,2017
10 卢立,刘辉,杨楚颢,等.益心酮渗透泵片的制备及体外释放度考察[J].中国医院药学杂志,2014,34(11):881-886
11 中国药典[S]. 2015年版.四部. 121-124
12 张冠男,白靖,曹德英.尼莫地平双层渗透泵片的制备及其体外释放度考察[J].中国药房,2012,23(29):2740-2743
13 李佳,郭玲,宋旭,等.硝苯地平双层渗透泵控释片的制备[J].华西药学杂志,2015,30(01):18-21