Novel aspects of wet milling for the production of microsuspensions and nanosuspensions of poorly water-soluble drugs

Document Type

Article

Publication Date

8-1-2011

Abstract

Micronization and nanoparticle production of poorly water-soluble drugs was investigated using single wet milling equipment operating in the attritor and stirred media modes. The drug particles in the median size range of 0.22 μm were prepared by changing the milling mode and operating conditions of a Micros mill with a purpose of elucidating the dynamics of the wet milling process. It was determined that particle breakage due to mechanical stresses and aggregation due to insufficient stabilization are two competing mechanisms which together control the wet milling dynamics of the poorly water-soluble drugs. The study in the attritor mode using four different classes of stabilizers with six drugs indicated that steric stabilization worked better than electrostatic stabilization for the drugs studied. In addition, the existence of different minimum polymer concentrations for the stabilization of microsuspensions and nanosuspensions was indicated. The major role of a non-ionic polymer during the production of fine particles is its stabilization action through steric effects, and no experimental evidence was found to support the so-called Rehbinder effect. Periodic addition of the polymer as opposed to the addition of the polymer at the start of milling process was introduced as a novel processing method. This novel method of polymer addition provided effective stabilization and breakage of drug particles leading to a narrower and finer particle size distribution. Alternatively, it may allow shorter processing time and lower overall power consumption of the milling process for a desired particle size. © 2011 Informa Healthcare USA, Inc.

Identifier

79960361236 (Scopus)

Publication Title

Drug Development and Industrial Pharmacy

External Full Text Location

https://doi.org/10.3109/03639045.2010.551775

e-ISSN

15205762

ISSN

03639045

PubMed ID

21323486

First Page

963

Last Page

976

Issue

8

Volume

37

Grant

0540855

Fund Ref

National Science Foundation

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