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Tuning physicochemical properties of theophylline by cocrystallization using the supercritical fluid enhanced atomization technique
Department of Chemical Engineering and Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa.
Department of Chemical Engineering and Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa.
Department of Chemical Engineering and Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa.
Luleå University of Technology, Department of Health Sciences, Medical Science.ORCID iD: 0000-0002-0654-5410
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2014 (English)In: Journal of Supercritical Fluids, ISSN 0896-8446, E-ISSN 1872-8162, Vol. 86, p. 129-136Article in journal (Refereed) Published
Abstract [en]

Formation of different micro- to nanosized cocrystals of theophylline is addressed by using the supercritical enhanced atomization (SEA) process. The experimental results presented here help to highlight how to prepare cocrystals of theophylline (TPL), using a supercritical fluid-based technique to accomplish the required physicochemical properties of that active pharmaceutical ingredient (API). The SEA process shows a strong versatility and feasibility towards the formation of highly pure theophylline cocrystals, using tetrahydrofuran as a solvent. The formation of TPL cocrystals with different types of morphology and dissolution behaviour/properties is induced by using different coformers, such as urea, saccharin, gentisic acid, salicylic acid, glutaric acid, sorbic acid, 1-hydroxy-2-naphthoic acid, oxalic acid, maleic acid and nicotinamide. The solubility of each coformer in the dissolution medium of phosphate-buffered saline (pH 7.4 at 25 °C), could determine the dissolving rate behaviour of the produced cocrystals. Consequently, the low-soluble coformers generate TPL cocrystals with a slow-dissolving rate, while the use of highly-soluble coformers produces faster-dissolving TPL cocrystals. Albeit the SEA process operating temperature influences the mean cocrystal particle size, this technique shows a high potential as an effective cocrystal screening tool.

Place, publisher, year, edition, pages
2014. Vol. 86, p. 129-136
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Other Health Sciences
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Health Science
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URN: urn:nbn:se:ltu:diva-8828DOI: 10.1016/j.supflu.2013.12.011ISI: 000333511100017Scopus ID: 2-s2.0-84892183277Local ID: 7605f252-0c29-4e63-a6b9-6b438b5bd2c6OAI: oai:DiVA.org:ltu-8828DiVA, id: diva2:981766
Note
Validerad; 2014; 20131227 (ysko)Available from: 2016-09-29 Created: 2016-09-29 Last updated: 2018-07-10Bibliographically approved

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