确定性筛选设计优化奥氮平片的处方和工艺

Optimization of Olanzapine Tablets' Formulation and Process Parameters Using Definitive Screening Design

关键词:  奥氮平片  确定性筛选设计  溶出曲线  处方  制粒工艺

Key words:  Olanzapine tablets  definitive screening design  dissolution profile  formulation  granulation process

摘要:

目的 研究奥氮平片处方和制备工艺。方法 用HPLC测定奥氮平片的奥氮平和有关物质含量，用光纤药物溶出度实时测定仪测定溶出曲线，用确定性筛选设计优化奥氮平片的处方和工艺。结果 微晶纤维素加入方式（内加或外加）和羟丙基纤维素用量对颗粒大小分布有显著影响，羟丙基纤维素用量和制粒搅拌速率对溶出曲线相似因子f₂有显著影响。经过优化得到的奥氮平片处方为奥氮平2.5%、乳糖78%、微晶纤维素10%（内加）、羟丙基纤维素4%、交联聚维酮5%、硬脂酸镁0.5%；制粒工艺参数：切割速度30 rps、搅拌速度3 rps、制粒时间5 min。结论 确定性筛选设计适用于奥氮平片处方和制备工艺的筛选和优化，根据确定性筛选设计确定的处方和制备工艺所制的奥氮平片，其溶出曲线与参比制剂相似，其含量均匀度和有关物质均符合中国药典2015年版标准。

Abstract:

OBJECTIVE To study the formulation and process parameters of Olanzapine tablets. METHODS The HPLC was used to assay the content of olanzapine and related compounds in Olanzapine tablets, and the real-time dissolution test apparatus of drug was used to determine the dissolution profile of Olanzapine tablets. The definitive screening design was used to optimize Olanzapine tablets' formulation and process parameters. RESULTS Intragranular or extragranular microcrystalline cellulose and the amount of hydroxypropyl cellulose in fomulation influenced the distribution of granule size significantly. The amount of hydroxypropyl cellulose in fomulation and the stirring speed in granulating significantly influenced the f₂ of dissolution profile in vitro between the generic Olanzapine tablets and the RLD. The optimized formulation of Olanzapine tablets was 2.5% of olanzapine, 78% of lactose, 10% of intragranular microcrystalline cellulose, 4% of hydroxypropyl cellulose, 5% of PVPP-XL, 0.5% of magnesium stearate. The optimized granulation process was 3 rps (stirring speed), 30 rps (cutting speed) and 5 min (granulation time). CONCLUSION The definitive screening design can be used to optimize Olanzapine tablets' formulation and process parameters. The dissolution profiles in vitro of Olanzapine tablets prepared according to the optimized formulation and process are similar with the RLD, and they meet the regulations of Chinese Pharmacopoeia 2015 on content uniformity and related compounds.