Insight into Thermally Induced Phase Transformations of Erythromycin A Dihydrate

Abstract

Thermal stress that pharmaceutical solids are exposed to during manufacturing can induce various phase transitions in bulk drug substances or excipients, resulting in altered dosage form performance. This paper reports on the thermally induced transformations of a macrolide antibiotic, erythromycin A dihydrate, investigated in situ by variable temperature powder X-ray diffractometry and hot-stage Raman spectroscopy. Erythromycin A dihydrate undergoes dehydration to isomorphic dehydrate, which then melts and recrystallizes to anhydrate. Raman spectroscopy was able to distinguish the two isomorphs of erythromycin A, the dihydrate and the dehydrate, thus offering a potential tool for in-process control of the drying process. The model fitting approach did not provide insight into the solid-state dehydration mechanism. However, the reaction mechanism was presented on the basis of crystal chemistry.

Crystal Morphology Engineering of Pharmaceutical Solids: Tabletting Performance Enhancement

“…This result suggests a reduced frequency of the (101) planes in the M and H crystals. EMAD is capable of forming an isomorphic dehydrate (16,25,26). Thus, the water content analysis was performed to verify the hydration state of the model API.…”

Solid‐state properties and relationship between anhydrate and monohydrate of baclofen

“…erythromycin dihydrate and theophylline monohydrate) that form a metastable form upon dehydration. 10,[13][14][15] In this study, no intermediate crystalline or amorphous form was detected during dehydration of baclofen monohydrate.…”

“…9,10 In addition, this analytical technique is emerging as a powerful tool for pharmaceutical process monitoring. 11 For this reason, Raman spectroscopy was also applied for the characterization of solid forms of baclofen in this study.…”

Solid forms of pharmaceuticals: Polymorphs, salts and cocrystals

“…Solution crystallization is also used to examine solvates and hydrates and their stability at various temperatures and solvent conditions. Solvates and hydrates can either be used as the final form of the API for formulation into a drug product or can be further processed by dehydration/desolvation sometimes yielding additional new forms [12,13]. The common methods used in recrystallization from a neat compound include sublimation, thermal treatment, crystallization from melt and dry/wet grinding.…”