处方工艺对瑞舒伐他汀钙片混合均匀度及含量均匀度的影响

Effect of Formulation and Technology on Blend Uniformity and Content Uniformity of Rosuvastatin Calcium Tablets

关键词:  瑞舒伐他汀钙片  直接压片  混合均匀度  含量均匀度

Key words:  rosuvastatin calcium tablets  direct compression  blend uniformity  content uniformity

摘要:

目的 研究处方中的辅料及工艺对瑞舒伐他汀钙片混合均匀度及含量均匀度的影响。方法 采用粉末直接压片工艺,通过单因素试验,考察处方中乳糖的型号、微晶纤维素的型号、乳糖与微晶纤维素的比例、钙盐的种类及交联聚维酮用量对混合均匀度及含量均匀度的影响;同时研究混合工艺对混合均匀度,压片工艺对含量均匀度的影响。结果 不同的乳糖型号(T80、PW80、315)、微晶纤维素型号(PH102、M102、102)、乳糖与微晶纤维素的比例(1:1、3:1、1:3)、钙盐的种类[磷酸钙(细颗粒)、无水磷酸氢钙(细颗粒、细粉)、碳酸钙(细粉)]的处方混合均匀度及含量均匀度良好,磷酸钙(粗颗粒)的处方混合均匀度及含量均匀度较差。在混合容器中加入50%的乳糖,之后加入原料药、微晶纤维素、交联聚维酮和磷酸钙,以10 r·min^-1混合20~25 min;再加入剩余的乳糖,以10 r·min^-1混合15~25 min,物料混合均匀度良好。重力加料器及压片速度10~20 r·min^-1的含量均匀度良好;强制加料器及压片速度30 r·min^-1的含量均匀度较差。结论 通过研究筛选出了适合粉末直压工艺的乳糖型号、微晶纤维素型号、乳糖与微晶纤维素比例、钙盐种类及交联聚维酮用量。考察了混合工艺参数范围,优选了重力加料器及压片速度(10~20 r·min^-1),获得了良好的混合均匀度和含量均匀度。

Abstract:

OBJECTIVE To study the influence of the excipients in formulation and technology on the blend uniformity and content uniformity of rosuvastatin calcium tablets. METHODS Used the powder direct compression technology, through single factor experiment, the types of lactose, the types of microcrystalline cellulose, the ratios of lactose to microcrystalline cellulose, the types of calcium salt and the dosages of crospovidone were investigated for the influence of the blend uniformity and content uniformity. The influence of blending process on the blend uniformity and the influence of tableting process on the content uniformity were studied. RESULTS There were good blend uniformity and content uniformity on types of lactose(T80, PW80, 315), types of microcrystalline cellulose(PH102, M102, 102), different ratios of lactose to microcrystalline cellulose(1:1, 3:1, 1:3), types of calcium salt[calcium phosphate(fine particles), dibasic calcium phosphate anhydrous(fine particles, fine powder), calcium carbonate(fine powder)] and dosages of crospovidone, but a poor result on calcium phosphate(coarse particles). Added 50% lactose to the mixing container, added active pharmaceutical ingredient, microcrystalline cellulose, crospovidone and calcium phosphate, mixed at 10 r·min^-1 for 20-25 min; then added the remaining lactose and mixed at 10 r·min^-1 for 15-25 min, the blend uniformity was good. The content uniformity of gravity feeder and tableting speed(10-20 r·min^-1) was good, but a bad result on forced feeder and tableting speed(30 r·min^-1). CONCLUSION The types of lactose and microcrystalline cellulose, ratios of lactose to microcrystalline cellulose, types of calcium salt and dosages of crospovidone suitable for the powder direct compression process are selected through research. The range of blending process parameters is investigated, and the gravity feeder and tableting speed(10-20 r·min^-1) are optimized to obtain good blend uniformity and content uniformity.