基于D-最优混料试验设计的挤出搓圆法制备丸剂的复合辅料研究

Study on composite excipients for preparing pill by extrusion/rounding method based on D-optimal mixture design

目的:优选适于挤出搓圆法制备丸剂的复合辅料,探索影响丸剂成型质量的丸条的关键物理属性。方法:以微晶纤维素(MCC)、羧甲基纤维素钠(CMC-Na)、羟丙甲纤维素(HPMC-E5)的用量为考察因素,以工艺得率、圆整度、溶散时限、脆碎度、出条速度为考察指标,利用总评归一值(OD)为综合评价指标,采用D-最优混料试验设计方法对复合辅料进行优化;运用主成分分析(PCA-X)和正交偏最小二乘-判别分析(OPLS-DA),探索与制剂质量相关的丸条的关键物理属性。结果:优化得出最佳辅料配比为MCC(g)∶HPMC-E5(g)=1∶1;PCA-X和OPLS-DA结果显示,内聚性、黏性、破裂力、咀嚼性、压缩力、回复力是影响丸剂成型质量的丸条的关键物理属性。结论:本研究方法优化得到的复合辅料工艺稳定,丸剂成型质量好,且可通过丸条的物理性质来优化辅料配比,预测丸剂的成型质量。

Objective:To optimize the composite excipients which is suitable for preparing pill by the extrusion/rounding method,and explore the key physical properties of pill strip affecting pill forming quality.Methods:Taking the dosage of microcrystalline cellulose(MCC),carboxymethylcellulose sodium(CMC-Na)and hypromellose(HPMC-E5)as the investigation factors,the yield,circularity,disintegration time,friability and extrusion velocity as the investigation indexes,and the value of overall desirability(OD) as the comprehensive evaluation index,the composite excipients were optimized by the D-optimal mixture design. The principle component analysis(PCA-X)and orthogonal partial least squares-discriminant analysis(OPLS-DA)were used to explore the key physical properties of pill strip associated with the preparation quality.Results:The optimal excipients proportioning was MCC(g)∶HPMC-E5(g)=1∶1. The results of PCA-X and OPLS-DA showed that,cohesion,viscosity,cracking force,chewiness,compression force and recovery force were the key physical properties of pill strip affecting the forming quality of pill.Conclusion:The optimized composite excipients have the advantages of stable process and good pill forming quality. It is possible to optimize the excipients proportioning and predict the forming quality of pill through the characterization of physical properties of pill strip.