ISBN 9783843947923

978-3-8439-4792-3, Reihe Thermodynamik

Joscha Brinkmann
Thermodynamics of Lipid-Based Drug Delivery Systems

180 Seiten, Dissertation Technische Universität Dortmund (2021), Softcover, A5

Zusammenfassung / Abstract

The low water solubility of active pharmaceutical ingredients and often poor bioavailability is one challenging task for the pharmaceutical industry.

Among others the bioavailability of these active pharmaceutical ingredients can be increased by lipid-based drug delivery systems. Herein the active pharmaceutical ingredient is dissolved in a mixture of oils (often triglycerides) and further excipients. The lipid-based drug delivery system aims at preventing the active pharmaceutical ingredient from crystallizing during its transition via the gastrointestinal tract. Therefore, knowledge of the solubility of the active pharmaceutical ingredient as well as the performance of the formulation in the gastrointestinal tract is key to develop efficient lipid-based drug delivery systems.

Solubilities of active pharmaceutical ingredients were investigated in pure triglycerides, which differ in carbon chain length and number of double bonds in their carbon chains. Subsequently, a modeling approach was applied, which enables estimating the triglyceride compositions in natural edible oils. This approach further allows to assess the impact of the triglyceride composition on the solubility of active pharmaceutical ingredients (so called batch-to-batch consistency) by using predictive modeling with the Perturbed-Chain Statistical Associating Fluid Theory. An in-silico solubility screening was developed, which enables rapid identification of promising formulation types, to efficiently develop lipid-based drug delivery systems. Furthermore, the partitioning of an active pharmaceutical ingredient between lipid-based drug delivery systems and water during in-vitro partitioning tests was predictively modeled. The maximum amount of the active pharmaceutical ingredient in a lipid-based drug delivery system, which still avoids crystallization of the active pharmaceutical ingredient during a partitioning test, was predicted.