Development of miniaturized dissolution methodologies for rapid screening of amorphous solid dispersions: Proof of concept of an innovative High-throughput screening approach

Joana Branco Amante Macedo Veríssimo

Key information

Authors:

Joana Branco Amante Macedo Veríssimo (Joana Branco Amante Macedo Veríssimo)

Supervisors:

Hermínio Albino Pires Diogo (Hermínio Albino Pires Diogo); Luís Filipe Ramalho de Almeida e Sousa

Published in

12/06/2021

Abstract

Amorphous solid dispersions (ASD) are in the forefront of drug delivery systems for being a strategy to overcome solubility challenges posed by poorly water-soluble compounds, by combining the benefits of an amorphous API with the stabilization provided by a polymeric matrix. This project consisted in the development of novel miniaturized screening methodologies for high-throughput screening (HTS) to study the dissolution of ASD prototypes during early stages of formulation development and to identify the most promising candidates in terms of maximum drug exposure generated upon dissolution. A solvent evaporation and a fusion method have been developed for the preparation of ASD films on a deposition platform (Hovione Intellectual Property) fitted to the wells of a 24-well quartz microplate. The ASD prototype experimental set was formed upon combination of a model drug, Indomethacin (IND), with a pool of eight polymers (HPMCAS-HF, EUDRAGIT EPO, EUDRAGIT L100-55, PVP K29/32. KOLLIDON K30, COPOVIDONE K28, HPMC E3, HPMC E5), at four distinct drug loads (30, 50, 60 and 80% w/w). Dissolution testing was monitored in real-time by UV-Vis spectroscopy via microplate reader using Phosphate buffer solutions (PBS) at pH 2.0 and pH 6.8 as dissolution media. Biorelevant dissolution studies were conducted in FaSSGF (pH 1.6) and, upon transition, in FaSSIF (pH 6.5). Dynamic Light Scattering (DLS) was used to investigate phase separation phenomena occurring in solution at higher supersaturation states. Confocal Raman Microscopy (CRM) was applied to evaluate uniformity of deposition and phase separation within the ASD films.