Controlling particle size of a poorly water-soluble drug using ultrasound and stabilizers in antisolvent precipitation

Document Type

Article

Publication Date

8-19-2009

Abstract

The objective of this work was to develop a better understanding of a potentially scalable, liquid antisolvent (LAS) precipitation process, for the preparation of stable aqueous suspensions of ultrafine particles of poorly water- soluble active pharmaceutical ingredients (APIs). A novel combination of jets, ultrasound, polymers, and surfactants was used for the precipitation and stabilization of ultrafine particles of griseofulvin (GF). Use of ultrasound and high stream velocities enhances micromixing, whereas addition of polymers/surfactants inhibits/lowers the particle growth. A combination of ultrasound, high jet velocities, and stabilizers decreased the GF particle size to 1.04 μm (±0.46 μm) from 30.8 μm(±14.2 /an), when none of the treatments were used. A rational understanding was developed for predicting process performance and selecting suitable particle growth inhibitors/stabilizers. Favorable process conditions and combinations of polymer and surfactants were also identified experimentally for the precipitation of ultrafine particles of GF with a narrow particle size distribution (PSD). © 2009 American Chemical Society.

Identifier

69249164683 (Scopus)

Publication Title

Industrial and Engineering Chemistry Research

External Full Text Location

https://doi.org/10.1021/ie900248f

ISSN

08885885

First Page

7581

Last Page

7593

Issue

16

Volume

48

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