Repurposing Melt Degradation for the Evaluation of Mixed Amorphous-Crystalline Blends

Sumayah Abdul-jabbar, Daniel W. Wong, Gary P. Martin, Brendon Woodhead, Paul G. Royall*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

Medicine regulators require the melting points for crystalline drugs, as they are a test for chemical and physical quality. Many drugs, especially salt-forms, suffer concomitant degradation during melting; thus, it would be useful to know if the endotherm associated with melt degradation may be used for characterising the crystallinity of a powder blend. Therefore, the aim of this study was to investigate whether melt-degradation transitions can detect amorphous content in a blend of crystalline and amorphous salbutamol sulphate. Salbutamol sulphate was rendered amorphous by freeze and spray-drying and blended with crystalline drug, forming standards with a range of amorphous content. Crystalline salbutamol sulphate was observed to have a melt-degradation onset of 198.2±0.2°C, while anhydrous amorphous salbutamol sulphate prepared by either method showed similar glass transition temperatures of 119.4±0.7°C combined. Without the energy barrier provided by the ordered crystal lattice, the degradation endotherm for amorphous salbutamol sulphate occurred 50°C below the melting point, with an onset of 143.6±0.2°C. The enthalpies for this degradation transition showed no significant difference between freeze- and spray-dried samples (p>0.05). Distinct from convention, partial integration of the crystalline melt-degradation endotherm was applied to the region 193–221°C which had no contribution from the degradation of amorphous salbutamol sulphate. The linear correlation of these partial areas with amorphous content, R2=0.994, yielded limits of detection and quantification of 0.13% and 0.44% respectively, independent of drying technique. Melt-degradation transitions may be re-purposed for the measurement of amorphous content in powder blends, and they have potential for evaluating disorder more generally.

Original languageEnglish
Article number105
JournalAAPS PharmSciTech
Volume22
Issue number3
DOIs
Publication statusPublished - Apr 2021

Keywords

  • amorphous content
  • amorphous-crystalline blends
  • differential scanning calorimetry
  • melt degradation
  • salbutamol sulphate

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