Development of Fixed Dose Combinations using Advanced Engineering Technologies

Student thesis: Doctoral ThesisDoctor of Philosophy

Abstract

Traditionally manufacturing of drug formulations has been controlled by an established regulatory framework which ensured that final product quality was safeguarded. By carrying out testing of batch-based operations and comparison with raw material and end-product characteristics this quality is guaranteed. However, in recent years there has been increased interest in improving both the safety and the quality of formulated medications while simultaneously cutting costs. The industry has looked to move away from batch processing and towards continuous manufacturing.

Commonly used continuous manufacturing techniques including; hot-melt extrusion, spray-drying and hot-melt co-extrusion were employed throughout this thesis in order to produce fixed-dose combination products. Depending on the desired characteristics of the final formulation, selection of appropriate continuous manufacturing platform had a critical impact on the overall outcome. Several continuous manufacturing platforms, with particular focus on hot-melt extrusion, were successfully employed throughout this thesis, highlighting it as an advanced, engineering technology to produce fixed-dose combinations for the treatment of hypertension and to improve adherence.

Furthermore, a range of anti-hypertensive drugs were used throughout various chapters. These active pharmaceutical ingredients presented a range of therapeutic and manufacturing problems including; poor water solubility, thermolability or having a short half-life. Additional investigations were also carried out in order to overcome identified problems as they were met during the course of this research program including; swelling behaviour of polymeric carriers or to make use DOE and PAT in order to obtain a truly continuous manufacturing platform.
Date of AwardDec 2020
Original languageEnglish
Awarding Institution
  • Queen's University Belfast
SupervisorGavin Andrews (Supervisor) & Shu Li (Supervisor)

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