肠康宁多元释药片剂的制备工艺研究

Study on the preparation of Changkangning multi-release tablets

目的:以肠康宁为模型药物,制得胃溶型的黄芪片和pH敏感-酶触发型黄连片,从而达到多元释药、标本兼治的目的。方法:压片过程中采用湿法制颗粒后压片,根据浸膏性质选择适宜辅料配比或/和辅料加入方式,以片芯的硬度、崩解时限等为考察指标,完成压片步骤;采用多层包衣法,以盐酸小檗碱体外释放度等为考察指标,对包衣处方中成膜剂种类及比例、增塑剂种类及用量、包衣增重进行筛选。结果:黄芪片芯药辅比为黄芪浸膏:微晶纤维素(MCC):低取代羟丙甲基纤维素(L-HPC):硬脂酸镁=100:67.43:4:1,其中MCC向纯化液中加65%,整粒完成后加2.43%,L-HPC采用内外加法,内加2%,外加2%;黄连片芯药辅比为黄连浸膏:MCC:乳糖:L-HPC:硬脂酸镁=100:69.94:29.96:5:2。黄芪包衣工艺为:取EudragitE100,乙醇溶解,加15%的PEG-6000,配制成聚合物浓度为10%的包衣液,包衣增重4%;黄连包衣工艺为:先包聚合物浓度为10%的EudragitE100隔离层,再包质量浓度为2%、加聚合物干重5%的邻苯二甲酸二丁酯的壳聚糖溶液,最后包EudragitL30D55分散体比EudragitS100为1:5比例的pH敏感层(加入聚合物干重20%的柠檬酸三乙酯作增塑剂),最终测得包衣增重在7%时,黄连片能较好的达到结肠靶向释药的目的。结论:经体外溶出度试验,该制剂较好的达到多元释药目的。

Objective:Taking Changkangning as a model drug,gastric soluble Astragalus tablet and pH and enzymes dependent Coptis chinensis tablet were prepared through the research on tablet compressing conditions and coating conditions of Astragalus extract and extract of Coptis chinensis,which were multiple unit drug release and treating both the symptoms and root causes way.Method:Taking hardness of tablet and disintegration time limited as evaluation indicators,wet granulation was chosen before the tablet compressing,and the proper ratio of auxiliary material and the way added were selected according to the nature of the extract.During the coating,multilayer coating way was chosen.Using in vitro release of berberine hydrochloride as evaluation indicator,the category and proportion of film forming agent,the category and dosage of the plasticizer,the weight increment of coat were screened.Result:For the Astragalus tablet core,the ration was as following:extract:microcrystalline cellulose(MCC):L-HPC:magnesium stearate=100:67.43:4:1.65% MCC was added to the purified solution,and 2.43% was added after prettifying particles.L-HPC was added in inside and outside(2% of each way).For the Coptis chinensis tablet core,the ration was as following:extract:MCC:lactose:L-HPC:magnesium stearate=100:69.94:29.96:5:2.Astragalus tablet coating conditions were as following:Eudragit E100 was dissolved in ethanol and 15% PEG6000 was added to get a 10% polymer coating solution.And the coating weight was increased by 4%.Coptis chinensis tablet coating conditions as following:10% polymer Eudragit E100 was coated as isolated layer.Then chitosan solution dissolving in phthalate was coated whose mass concentration was 2% and dry weight of polymer was 5%.Then pH dependent layer was coated using Eudragit L30D55:Eudragit S100=1:5(20% dry weight of polymer of triethyl citrate as plasticizer).When the coating weight was increased by 7%,Coptis chinensis tablet can fulfill the aim of releasing in colon.Conclusion:The result of dissolution rate test in vitro proves the successful development of ChangKangning multi-release tablets.