复方替米沙坦双层片的制备工艺及其质量标准的研究
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摘要
目的：研制复方替米沙坦双层片的制备工艺和建立质量检测的方法。方法：采用正交实验，以氢氯噻嗪的溶出度参数Td为指标，优选氢氯噻嗪层的处方工艺；用均匀设计法，以双层片的脆碎度和崩解时限为指标，筛选替米沙坦层的辅料配比；采用高效液相测定氢氯噻嗪和替米沙坦的含量并制订质量标准。结果：复方替米沙坦双层片的最佳处方组成为内层含氢氯噻嗪12.5mg，乳糖46mg，微晶纤维素16mg，羧甲基淀粉钠4mg，以2％HPMC为粘合剂制粒，加入1％硬脂酸镁，压片；外层则为替米沙坦40mg，氢氧化钠3.36mg，葡甲胺12mg，山梨醇180mg，聚维酮k30 11.2mg，加入2％硬脂酸镁，压片。结论：所定双层片的处方合理，工艺可行，质量控制方法简便可靠。
Objective: To screen the best formulation composition of compound telmisartan bilayer tablets and to establish an analysis method to control quality. Method: The composition of hydrochlorothiazide layer were selected by orthogonal experiment, regarding the parameter of dissolution degree(Td) as index; the proportion of excipients of telmisartan layer were choosed by means of uniform design; Used HPLC method to determine the content of telmisartan and hydrochlorothiazide in compound telmisartan bilayer tablets simultaneously and established the quality standard. Result : Hydrochlorothiazide layer contained hydrochlorothiazide 12.5mg, lactose 46mg, microcrystalline cellulose 16mg, sodium starch glycolate 4mg, converting the whole to granules in the presence of 2% HPMC; telmisartan layer contained telmisartan 40mg, sodium hydroxide 3.36mg, meglumine 12mg, sorbitol 180mg, povidoneK30 11.2mg. Conclusion: The formulation of the bilayer tablets is reasonable, the preparation technology is feasible; the method of quality control is simple and reliable.
Objective: To screen the best formulation composition of compound telmisartan bilayer tablets and to establish an analysis method to control quality. Method: The composition of hydrochlorothiazide layer were selected by orthogonal experiment, regarding the parameter of dissolution degree(Td) as index; the proportion of excipients of telmisartan layer were choosed by means of uniform design; Used HPLC method to determine the content of telmisartan and hydrochlorothiazide in compound telmisartan bilayer tablets simultaneously and established the quality standard. Result : Hydrochlorothiazide layer contained hydrochlorothiazide 12.5mg, lactose 46mg, microcrystalline cellulose 16mg, sodium starch glycolate 4mg, converting the whole to granules in the presence of 2% HPMC; telmisartan layer contained telmisartan 40mg, sodium hydroxide 3.36mg, meglumine 12mg, sorbitol 180mg, povidoneK30 11.2mg. Conclusion: The formulation of the bilayer tablets is reasonable, the preparation technology is feasible; the method of quality control is simple and reliable.
引文
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[14] 方开泰．均匀设计与均匀设计表，北京：科学出版社，1994，6(1)．
[15] 王晋，黄群，马成禹，等．压片工艺定量化控制的研究．中国药学杂志，2000；35(9)：600～603．
[16] 平其能，等编著．现代药剂学，北京：中国医药科技出版社，1998，10(1)：275．
[2] Boehringer Ingelheim Micardis HCT说明书.
[3] 柯娟娟．替米沙坦研究进展及市场．中国制药信息，2001；17(6)：6～9．
[4] The sixth report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure. Arch Intern Med, 1997; 157(21): 2413～2446.
[5] Sica DA, Fixed-dose combination antibypertensive drugs: principles and practice. Cardivasc Rev Rep, 1997;18(9):28～46.
[6] 孙忠实．新型AT拮抗剂-替米沙坦．中国新药杂志，1999：8(12)：801～802．
[7] 替米沙坦急性毒性试验资料(内部资料)．
[8] 张贵卿．吕爱刚．张玲，等．药物应用与毒理数据．河南医科大学出版社，1999：4(1)：262．
[9] McGill JB, Reilly PA Telmisartan plus hydrochlorothiazide versus telmisartan or hydrochlorothiazide monotherapy in patients with mild to moderate hypertension: a multicenter, randomized, double-blind, placebo-controlled, parallel-group trial. Clin Ther 2001; 23(6):833～850.
[10] 中国药典2000版二部附录．
[11] 方有杰，赵赶，唐秀能，等．氢氯噻嗪片的体外溶出度考察．儿科药学杂志，1999：5(1)：12～13，21．
[12] 苗爱东，吴锦健，崔玉琴，等．布洛芬片剂处方组成的优选．中国医院药学杂志，1995；15(6)：266～267．
[13] 专利USP6071939．
[14] 方开泰．均匀设计与均匀设计表，北京：科学出版社，1994，6(1)．
[15] 王晋，黄群，马成禹，等．压片工艺定量化控制的研究．中国药学杂志，2000；35(9)：600～603．
[16] 平其能，等编著．现代药剂学，北京：中国医药科技出版社，1998，10(1)：275．