Role of Crystal Disorder and Mechanoactivation in Solid-State Stability of Pharmaceuticals

Jayant Iyer, Michael Brunsteiner, Dattatray Modhave, Amrit Paudel*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

Abstract

Common energy-intensive processes applied in oral solid dosage development, such as milling, sieving, blending, compaction, etc. generate particles with surface and bulk crystal disorder. An intriguing aspect of the generated crystal disorder is its evolution and repercussion on the physical- and chemical stabilities of drugs. In this review, we firstly examine the existing literature on crystal disorder and its implications on solid-state stability of pharmaceuticals. Secondly, we discuss the key aspects related to the generation and evolution of crystal disorder, dynamics of the disordered/amorphous phase, analytical techniques to measure/quantify them, and approaches to model the disordering propensity from first principles. The main objective of this compilation is to provide special impetus to predict or model the chemical degradation(s) resulting from processing-induced manifestation in bulk solid manufacturing. Finally, a generic workflow is proposed that can be useful to investigate the relevance of crystal disorder on the degradation of pharmaceuticals during stability studies. The present review will cater to the requirements for developing physically- and chemically stable drugs, thereby enabling early and rational decision-making during candidate screening and in assessing degradation risks associated with formulations and processing.

Original languageEnglish
Pages (from-to)1539-1565
Number of pages27
JournalJournal of Pharmaceutical Sciences
Volume112
Issue number6
Early online date25 Feb 2023
DOIs
Publication statusPublished - Jun 2023

Keywords

  • Amorphization
  • Crystal disorder
  • Degradation
  • Glass transition
  • Mechanoactivation
  • Plasticization
  • Recrystallization
  • Stability

ASJC Scopus subject areas

  • Pharmaceutical Science

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