Datenbestand vom 23. März 2024

Warenkorb Datenschutzhinweis Dissertationsdruck Dissertationsverlag Institutsreihen     Preisrechner

aktualisiert am 23. März 2024

ISBN 9783843929677

84,00 € inkl. MwSt, zzgl. Versand


978-3-8439-2967-7, Reihe Thermodynamik

Linda Lange
Phase Behavior of Pharmaceutical Cocrystals (Band 23)

218 Seiten, Dissertation Technische Universität Dortmund (2016), Softcover, A5

Zusammenfassung / Abstract

The formation of pharmaceutical cocrystals (CCs) is an emerging method to meet the requirements on solubility and dissolution behavior of active pharmaceutical ingredients (APIs). These CCs are crystalline solids that consist of the API and at least one coformer (CF) in a defined stoichiometry. In industrial scale, CC formation is performed by crystallization from solution, which is often affected by pH-dependent dissociation, polymorphic transitions, as well as by formation of hydrates and salts. Therefore, the purpose of this work is to increase the efficiency of the CC formation processes by a thermodynamically correct description of the CC phase behavior.

The presented modeling procedure comprises solubility-line calculations of the API, CF, and the CC itself, allowing for the real interactions between solutes and solvents by using the Perturbed-Chain Statistical Associating Fluid Theory (PC-SAFT). The CC solubility was modeled applying a solubility product based on the knowledge of only a single experimental solubility data point in any solvent. Using this information, the CC solubility in other solvents and even solvent mixtures was predicted without need of additional data. Furthermore, based on the Gibbs-Helmholtz equation, the model was applied to predict the CC solubility at other temperatures. In aqueous solutions, the increase of solubility by pH change was considered accounting for the dissociation equilibria, whereas the solubilities of hydrates and salts were again calculated by applying solubility products. On top of that, the proposed approach enabled the description of the complex phase behavior of CC systems exhibiting polymorphic transitions.

The modeling results were verified by experimental data. PC-SAFT is shown to be able to correlate and predict solubilities of CCs, hydrates, salts, and polymorphs for all considered CC systems correctly. Thus, the proposed approach allows for a reliable description of the CC phase behavior with a minimal experimental effort, which in turn results in a more efficient CC formation.