Physicochemical aspects of drug release. XVI. The effect of storage on drug dissolution from solid dispersions and the influence of cooling rate and incorporation of surfactant

Abstract

Solid dispersions of 10% w w griseofulvin were prepared with polyethylene glycol (PEG) 3000 or xylitol as carriers, with or without the incorporation of 2% w w sodium dodecyl sulphate (SDS). The dispersions were cooled either slowly at room temperature or rapidly in liquid nitrogen. The dispersions were stored under controlled conditions at 25, 35 and 45°C and dissolution rate studies, particle size measurements, phase analysis and heat of fusion measurements were performed at intervals during 10 months. In dispersions with PEG as carrier, without SDS, griseofulvin was present in crystalline form. The dissolution rate was unchanged during storage for dispersions prepared with slow cooling, but decreased for dispersions prepared with rapid cooling. This may have been caused by an increase in PEG crystallinity with storage time. With the incorporation of SDS, the dissolution rate initially increased considerably for dispersions with PEG as carrier. Griseofulvin was dissolved in the carrier/ surfactant system in dispersions prepared with slow cooling, whereas griseofulvin was present in pure crystalline form in corresponding dispersions prepared with rapid cooling. Dispersions stored at 45°C liquified on storage independent of cooling procedure and were excluded from the study. The dissolution rate decreased considerably for dispersions prepared with slow cooling, since the dissolution of PEG was impaired by the incorporation of SDS. The dissolution rate of dispersions prepared with rapid cooling also decreased with storage temperature. Griseofulvin was present in crystalline form in all dispersions with xylitol as carrier and the dissolution rate and particle size remained unchanged irrespective of storage temperature and time. The dissolution rate was increased with the incorporation of SDS, but not to the same extent as in PEG dispersions. With increase in storage temperature the dissolution rate decreased, because of decreased dissolution of xylitol with the incorporation of SDS.