Modeling fluidized bed impregnation of active pharmaceutical ingredients onto porous excipients

摘要

Impregnation of active pharmaceutical ingredients (APIs) onto porous excipients offers several advantages to solid dosage pharmaceutical preparation over conventional formulation methods. Previous work has successfully introduced fluidized bed (FB) impregnation of APIs onto porous carriers as a robust manufacturing process with numerous benefits (easy to implement, excellent blend uniformity and dissolution kinetics, stabilization of amorphous APIs). This study aims to develop a simple, multi-scale modeling approach to FB impregnation. The model consists of three main parts: (1) an energy/mass balance on the FB and an evaporative flux calculation, (2) an impregnation model for a single particle and (3) a drying model for a single particle. The model allows the calculation of some important process parameters (e.g. product temperature, maximum liquid spray rate) for given drying conditions. These are important process parameters needed to achieve successful impregnation. The model accounts for convection, diffusion and crystallization within the particle. The main characteristic is the 2D modeling of the liquid and API distributions within the particle during impregnation and drying. Several cases are presented to illustrate the effect of some material properties (fast crystallization, slow diffusion, low porosity) on the final API profile. Simulation results regarding API profiles of impregnation are in a very good agreement with experimental measurements carried out in our previous work. (C) 2019 Elsevier Ltd. All rights reserved.