Solvent influences on metastable polymorph lifetimes: real-time interconversions using energy dispersive X-ray diffractometry.

Solvent influences on the crystallization of polymorph and hydrate forms of the nootropic drug piracetam (2-oxo-pyrrolidineacetamide) were investigated from water, methanol, 2-propanol, isobutanol, and nitromethane. Crystal growth profiles of piracetam polymorphs were constructed using time-resolved diffraction snapshots collected for each solvent system. Measurements were performed by in situ energy dispersive X-ray diffraction recorded in Station 16.

Evaluation of drug physical form during granulation, tabletting and storage.

An active pharmaceutical ingredient (API) was found to dissociate from the highly crystalline hydrochloride form to the amorphous free base form, with consequent alterations to tablet properties. Here, a wet granulation manufacturing process has been investigated using in situ Fourier transform (FT)-Raman spectroscopic analyses of granules and tablets prepared with different granulating fluids and under different manufacturing conditions. Dosage form stability under a range of storage stresses was also investigated.

Quantification of crystalline forms in active pharmaceutical ingredient and tablets by X-ray powder diffraction.

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 degrees C/75% relative humidity in open containers.

Further investigations into the use of high sensitivity differential scanning calorimetry as a means of predicting drug-excipient interactions.

The early prediction of drug-excipient incompatibility is vital in the pharmaceutical industry to avoid costly material wastage and time delays. We report here on the use of high sensitivity differential scanning calorimetry (HSDSC) to examine the compatibility between an experimental drug (Drug A) and common pharmaceutical excipients. Short-term HSDSC experiments (up to 25h) indicated that Drug A was stable in the presence of moisture and was compatible with both lactose monohydrate and magnesium stearate in the dry state, but showed degradation in the presence of magnesium stearate and water in combination.

Effect of moisture on polyvinylpyrrolidone in accelerated stability testing.

Accelerated stability studies are a common approach for predicting the long-term stability of pharmaceutical formulations. However, in this study, a slowing of dissolution was observed for a formulation following storage at elevated temperature and humidity. The moisture sorption isotherm for the binder, polyvinylpyrrolidone (PVP), shows absorption of a significant quantity of water on exposure to elevated humidity.