Enhanced physical stability of amorphous drug formulations via dry polymer coating

Maxx Capece, Rajesh Davé

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2076-2084
Number of pages9
JournalJournal of Pharmaceutical Sciences
Volume104
Issue number6
DOIs
StatePublished - Jun 1 2015

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

Keywords

  • Amorphous
  • amorphization
  • coating
  • crystallization
  • dry polymer coating
  • formulation
  • physical stability
  • surface-enhanced crystallization

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