Open AccessQuantification of crystalline forms in active pharmaceutical ingredient and tablets by X‐ray powder diffraction
Author(s) -
Cooper V. Brett,
Pearce Gareth E. S.,
Petts Catherine R.
Publication year - 2003
Publication title -
journal of pharmacy and pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.745
H-Index - 118
eISSN - 2042-7158
pISSN - 0022-3573
DOI - 10.1211/0022357021675
Subject(s) - active ingredient , powder diffraction , ingredient , relative humidity , diffraction , materials science , dosage form , x ray , chemical engineering , chemistry , crystallography , chromatography , optics , thermodynamics , physics , food science , medicine , engineering , pharmacology
ABSTRACT A Merck development compound was known to exist in several polymorphic forms, hydrates and solvates. The polymorphic forms were characterized and the most thermodynamically stable form at room temperature was identified and taken into development. During routine stability analysis it became apparent that the crystalline form of the compound was converting from one form to another in tablets that were stored at 40° C/75% relative humidity in open containers. This form conversion did not occur when the active pharmaceutical ingredient (API) alone was stored under these conditions. This paper describes the development and application of an X‐ray powder diffraction method for the determination of the relative content of the two crystalline forms in API and within the final formulation. Results of monitoring the crystalline form conversion are reported and a possible mechanism of conversion is postulated.