通过推进剂辅助雾化进行纳米尺寸控制和表面改性可提高雌二醇的溶解度和溶出度。

Nanosizing and Surface Modification by Propellant Assisted Aerosolization Enhances Solubility and Dissolution of Estradiol.

作者信息

Jain Gaurav K, Chaudhary Gaurav, Rahman Mohammad Akhlaquer, Warsi Musarrat Husain, Imran Mohammad

机构信息

Centre for Advanced Formulation Technology, Delhi Pharmaceutical Sciences and Research University, New Delhi, 110017, India.

Department of Pharmaceutics, DIPSAR Campus, Delhi Pharmaceutical Sciences and Research University, Pushp Vihar, New Delhi, India.

出版信息

AAPS PharmSciTech. 2025 Jun 6;26(5):165. doi: 10.1208/s12249-025-03151-2.

DOI:10.1208/s12249-025-03151-2

PMID:40481369

Abstract

OBJECTIVE

A novel method for the development of uniform, nanosized, crystalline particles of estradiol valerate (EV) by the propellant assisted aerosolization (PAA) technique as an alternative to supercritical carbon dioxide assisted atomization is described.

METHODS

HFA 134a was used as a propellant. PAA process parameters such as nozzle diameter, pre-expansion pressure, and hot air pressure were optimized using 33 factorial Box-Behnken design for the preparation of uniform, nanosized EV (nano-EV). Nano-EV was characterized for physicochemical properties, crystallinity and enhancement of the solubility and dissolution.

RESULTS

The nano-EV, produced by the PAA technique, showed loose cuboidal aggregates with smooth surface morphology. PAA with 0.22 µm nozzle diameter, 120 psi pre-expansion pressure and 80 psi hot air pressure, yielded uniform (PDI, 0.27 ± 0.05) nano-EV particles with mean size of about 291 ± 5.8 nm. FTIR and DSC confirmed that no physical or chemical change occurred during nanosizing. XRD data showed that nano-EV particles were crystalline. The results demonstrated nearly twofold higher solubility and 2.3-fold enhanced dissolution of nano-EV compared to EV.

CONCLUSION

The PAA process is a cost effective and scalable technique and has a potential industrial application for producing nanocrystals of BCS class II drugs.

摘要

目的

描述一种通过推进剂辅助雾化（PAA）技术制备戊酸雌二醇（EV）均匀纳米级结晶颗粒的新方法，作为超临界二氧化碳辅助雾化的替代方法。

方法

使用HFA 134a作为推进剂。采用33析因Box-Behnken设计优化PAA工艺参数，如喷嘴直径、预膨胀压力和热风压力，以制备均匀的纳米级EV（纳米EV）。对纳米EV的理化性质、结晶度以及溶解度和溶出度的提高进行了表征。

结果

通过PAA技术制备的纳米EV呈现出表面形态光滑的松散长方体聚集体。在喷嘴直径0.22 µm、预膨胀压力120 psi和热风压力80 psi的条件下，PAA产生了均匀（多分散指数，0.27±0.05）的纳米EV颗粒，平均粒径约为291±5.8 nm。傅里叶变换红外光谱（FTIR）和差示扫描量热法（DSC）证实，在纳米化过程中未发生物理或化学变化。X射线衍射（XRD）数据表明纳米EV颗粒是结晶的。结果表明，与EV相比，纳米EV的溶解度提高了近两倍，溶出度提高了2.3倍。