Some factors influencing dissolution from salicylic acid-urea solid dispersions.

Abstract

Solid dispersion systems of salicylic acid-urea have been prepared using a fusion method. Two different methods of cooling the melt were employed, rapid cooling in liquid nitrogen and slow cooling in air. Differential scanning calorimetry and an X-ray diffraction technique were employed to investigate the nature of the fused mixture. Evidence was found of compound formation between the constituents. Dissolution rates of drug from non-disintegrating discs of solid dispersion systems were measured. Rapid cooling of the melt resulted in a much faster drug dissolution rate than from a corresponding mixture prepared by a slow cooling method. This phenomenon is explained by a difference in the sizes of drug particles produced under the different cooling conditions. Rapid cooling favoured the generation of many nucleation sites for the solid drug particles as the liquid was cooled, and hence many small particles were obtained. Conversely, slow cooling favoured the growth of the first few nuclei or solid drug particles, rather than the production of new nuclei, and hence large drug particles were obtained.