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

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.