全因子实验设计筛选米诺膦酸片处方及其混合均匀性考察

Screening the Formulation of Minodronic Acid Tablets by Full Factorial Experimental Design and Investigation on Its Blend Uniformity

关键词:  米诺膦酸片  全因子实验设计  ASTM E2709/E2810  分层取样  混合均匀性

Key words:  minodronic acid tablets  full factorial experimental design  ASTM E2709/E2810  stratified sampling  blend uniformity

摘要:

目的 筛选米诺膦酸片的最优处方，并确认其混合均匀性。方法 根据原研制剂的处方组成，使用Minitab 19软件对各辅料的处方用量进行优化，以溶出度和含量均匀性为考察指标，进行全因子实验设计和分析。依据ASTM E2709/E2810对本品进行分层取样，统计分析其颗粒的混合均匀性和成品的含量均匀性。结果 筛选得到原料粒径D (90)范围为11~15 μm，淀粉占比9%，乳糖占比79.5%，羟丙基纤维素占比10%组成最优处方。小中放批样品总混工序混合均匀性取样样品和压片过程中分层取样样品经统计学分析混合均匀性可被接受。结论 筛选的米诺膦酸片处方合理、工艺可行，能确保该小规格片剂的溶出度和含量均匀性。

Abstract:

OBJECTIVE To screen the optimal formulation of minodronic acid tablets and confirm its blend uniformity. METHODS According to the formulation of the innovator products, Minitab 19 software was used to design and analyze the optimization experiment of the formulation dosage of each excipient, taking the dissolution and content uniformity as inspection indicators, the full factorial experimental design and analysis were carried out. According to ASTM E2709/E2810, stratified sampling was used, and the blend and content uniformity was statistically analyzed. RESULTS After screening, the optimal particle size distribution of active pharmaceutical ingredient was D90(11 to 15 μm), the optimal proportion of starch, lactose and hydroxypropyl cellulose was 9%, 79.5% and 10% respectively. The statistical analysis results of small and pilot production batches showed that uniformity of samples from blending process and from tabletting process were acceptable. CONCLUSION The screened formulation and process of minodronic acid tablets are feasible and can guarantee the dissolution and content uniformity of the tablets with small strength.