Enhanced physical stability of amorphous drug formulations via dry polymer coating

Document Type

Article

Publication Date

6-1-2015

Abstract

Although amorphous solid drug formulations may be advantageous for enhancing the bioavailability of poorly soluble active pharmaceutical ingredients, they exhibit poor physical stability and undergo recrystallization. To address this limitation, this study investigates stability issues associated with amorphous solids through analysis of the crystallization behavior for acetaminophen (APAP), known as a fast crystallizer, using a modified form of the Avrami equation that kinetically models both surface and bulk crystallization. It is found that surface-enhanced crystallization, occurring faster at the free surface than in the bulk, is the major impediment to the stability of amorphous APAP. It is hypothesized that a novel use of a dry-polymer-coating process referred to as mechanical-dry-polymer-coating may be used to inhibit surface crystallization and enhance stability. The proposed process, which is examined, simultaneously mills and coats amorphous solids with polymer, while avoiding solvents or solutions, which may otherwise cause stability or crystallization issues during coating. It is shown that solid dispersions of APAP (64% loading) with a small particle size (28 μm) could be prepared and coated with the polymer, carnauba wax, in a vibratory ball mill. The resulting amorphous solid was found to have excellent stability as a result of inhibition of surface crystallization.

Identifier

84929170899 (Scopus)

Publication Title

Journal of Pharmaceutical Sciences

External Full Text Location

https://doi.org/10.1002/jps.24451

e-ISSN

15206017

ISSN

00223549

PubMed ID

25902736

First Page

2076

Last Page

2084

Issue

6

Volume

104

This document is currently not available here.

Share

COinS