Modeling dissolution of sparingly soluble multisized powders.
The dissolution of powder drugs, besides being a topic of utmost importance, especially for the sparingly soluble ones, is far from being well-explained. The purpose of the present study is, on the one hand, to obtain experimental dissolution profiles and, on the other hand, to analyze and process the data for dissolution modeling. Three different size fractions of a widely used sparingly soluble drug--ibuprofen--were fully characterized with regard to its particle size distribution, specific surface area, density, solubility, and diffusion coefficient. The dissolution profiles were obtained making use of a technique that counts and sizes particles--the Coulter counter technique--which is capable of following the number and size of the particles in suspension throughout time. The knowledge of these parameters allowed a critical study of the assumptions associated with the models currently used to describe the dissolution process. It was concluded that most of the assumptions were not valid for the present experimental conditions. This motivated the proposal of a new methodology, which uses the experimentally determined characteristics of the drug and takes into account the polydisperse nature of the powder. By applying an adequate dissolution equation to each of the many size classes in which the primary particle size distribution was divided, it was possible to obtain a large agreement between the simulated and the experimental dissolution profile.
de Almeida
L P
LP
Laboratório de Galénica e Tecnologia Farmacéutica, Facuìdade de Farmácia, Universidade de Coimbra, Portugal.
Simöes
S
S
Brito
P
P
Portugal
A
A
Figueiredo
M
M
D008956:Models, Chemical; D011208:Powders / Q000737:chemistry*; D012995:Solubility
D011208:Powders