Characterization of an active pharmaceutical ingredient by its dissolution properties: amoxicillin trihydrate as a model drug.

To characterize the dissolution of particles, a dissolution rate coefficient alpha, consisting of a geometric factor gamma and material constant mu, was introduced. The impact of the particle geometry on the initial rate of dissolution was assessed for spherical, cubic and tetrahedral particles. Additionally, a description of dissolution of samples containing multiple populations of particles was derived. A two-population model was employed to characterize sieved fractions of amoxicillin trihydrate. The investigation, using factor analysis, of the influence of dose, particle size and agitation intensity on the dissolution rate coefficient alpha indicated the presence of disintegrating agglomerates in larger particles. Based on the dissolution characteristics of particular particle size fractions and on the determined particle size distribution, the dissolution profile of the mixed sample containing nine sieved fractions in size was successfully predicted. Finally, the limitations of the film theory are discussed in light of the multiple-population dissolution theory.