Solution Preparation in Pharmaceutical Processes: Dynamics and Dissolution models

Tiago Alexandre Duarte Faustino

Key information

Authors:

Tiago Alexandre Duarte Faustino (Tiago Alexandre Duarte Faustino)

Supervisors:

Carla Isabel Costa Pinheiro (Carla Isabel Costa Pinheiro); Tiago Miguel Porfirio Fonseca

Published in

12/10/2021

Abstract

The dissolution of powders in liquids is a state of the art procedure essential to support pharmaceutical processes such as chemical and biological reactions, crystallization, coating and spray drying operations. Nevertheless, the intention behind the applicability of pharmaceutical grade powder dissolution lies in the desire to obtain a clear solution in the absence of solids in the most efficient way. Traditionally, this step is performed in batch mode which depending of the material´s properties and the scale of the operation can take several hours or even days to be concluded. Thus, the feasibility, dynamics and applicability of dissolution models for a semi-continuous solution preparation process were studied to address all the shortcomings of traditional batch processing. Several dissolution tests were performed with different polymer-solvent pairs to establish a proof of concept while falling back on the aid of Process analytical technology (PAT) (viscometer, turbidimeter and refractive index (RI)) to asses some of the critical quality attributes (CQAs) and critical process parameter (CPPs) of the system. All trials performed presented a smooth dissolution with a dissolution time under 10 minutes while also reaching the target concentration. Additionally, residence time distributions (RTDs) were established using polymer powders as tracers under specific conditions. RTD modelling using ideal reactor also showed that viscosity is linked to the model itself. Lastly, some polymer dissolution models based on the complex diffusion of solvent penetration and chain disengagement mechanics from the particle to the bulk of the solution were capable of mimicking the experimental results.