儿童用氯氮平纳米混悬剂的制备及质量评价研究

Preparation and Quality Evaluation of Clozapine Nanosuspensions for Pediatric Use

关键词:  氯氮平  纳米混悬剂  制备工艺  体外释放

Key words:  clozapine  nanosuspensions  preparation process  in vitro release

摘要:

目的 制备一种儿童用氯氮平纳米混悬剂(clozapine nanosuspensions,CLZ-NS),优化处方与制备工艺,并对其进行质量评价。方法 采用纳米沉淀法制备CLZ-NS,正交试验筛选处方工艺,透射电镜观察CLZ-NS的微观形态,激光粒径测定仪测定纳米粒的粒径和多分散指数,释放试验评价其体外释放效果。结果 CLZ-NS最佳处方工艺为:CLZ与卵磷脂的质量比为1∶5,泊洛沙姆407用量为10 mg,有机相-水相(1∶5)；CLZ-NS呈球状分布,平均粒径为(98.78±2.37 ) nm,PDI为(0.155±0.027)。体外释放度研究表明CLZ-NS组在24 h体外累积释放度为78.92%,显著高于CLZ原料药组(32.97%),呈现快速释药的特性。结论 所确定的CLZ-NS处方合理、制备工艺简单,释放速度快,为其在儿童用药领域的应用奠定基础。

Abstract:

OBJECTIVE To prepare clozapine nanosuspensions (CLZ-NS) for pediatric use, optimize the formulation and preparation process, and evaluate their properties. METHODS The CLZ-NS was prepared by the nano-precipitation method, and then the formulation process was optimized by orthogonal design. The microstructure of CLZ-NS was observed by transmission electron microscopy. The particle size and polydispersity index of the nanoparticles were determined by granulometer. The in vitro release was evaluated by dissolution test. RESULTS The optimal formulation process of CLZ-NS was as follows: CLZ-to-lecithin ratio (1:5), the mass of Poloxamer 407 was 10 mg, organic phase-aqueous phase (1:5). CLZ-NS exhibited spherical morphology with an average particle size of (98.78±2.37) nm and a PDI of 0.155±0.027. The in vitro release study showed that the cumulative release of CLZ-NS group was 78.92% in 24 hours, which was significantly higher than that of CLZ raw material group (32.97%), showing a rapid release characteristic. CONCLUSION The determined CLZ-NS formulation is reasonable, the preparation process is simple, and the dissolution rate is fast, laying the foundation for its application in the field of pediatric medication.