Modeling Dissolution of Sparingly Soluble Multisized Powders

Abstract

0 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 drugsibuprofenswere 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 particlessthe Coulter counter techniqueswhich 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.

A Theoretical-Empirical Analysis on the Initial Dissolution Rate of Drugs from Polydispersed Particles

“…Various attempts have been made to simulate the effect of mean particle size on dissolution [10][11][12][13][14][15][16][17][18] ; however, at this time there is no universal approach for the specification of drug particle size due to insufficient understanding of the complex relationship between mean particle diameter and the dissolution rate of polydispersed particles. As an alternative to using representative particle diameters, dissolution from polydispersed particles can be modeled by dividing the particle sizes into 16 discrete fractions.…”

General solution for diffusion‐controlled dissolution of spherical particles. 2. Evaluation of experimental data

“…8,9,14,15 We decided to study single particle dissolution so that particle size distribution effects were eliminated from the dissolution behavior which should enhance our ability to evaluate the general particle dissolution model.…”

A novel approach for predicting the dissolution profiles of pharmaceutical tablets

“…In the last decades, 49 several empirical, semi-empirical and mechanistic mathematical 50 models have been proposed to describe the API dissolution profiles 51 from a variety of solid pharmaceutical dosage forms, e.g. matrix 52 systems [1][2][3], erodible tablets [4,5], microspheres [6], hydrogels 53 [7], powders [8] and immediate release tablets [9][10][11][12]. Siepmann 54 and Siepmann [13] gave a detailed review of the empirical, 55 semi-empirical and mechanistic mathematical models that have 56 been applied to describe the API dissolution profiles from solid 57 pharmaceutical dosage forms.…”

“…In their review, they pointed out, 58 that currently the predictive capability of empirical and 59 semi-empirical models is often quite low and the application of 60 mechanistic mathematical models that offer a deeper understand- 61 ing of API dissolution mechanism on a molecular scale is usually 62 difficult to apply due to their complexity [5]. In addition to that, 63 more and more new APIs are poorly soluble in water [14][15][16] 64 which makes it rather difficult to apply theoretical models to 65 describe their dissolution profiles as several steps are involved in 66 the complex dissolution process [8,[17][18][19]. Thus, the development 67 of a theoretical model that enables a deep insight into the dissolu-68 tion mechanism of these kinds of APIs, a sufficient applicability and 69 a high predictive capability is still challenging in pharmaceutical 70 science and development.…”