Sulfonic Acid Derivatives in the Production of Stable Co-Amorphous Systems for Solubility Enhancement.

Autor:	da Costa NF; iMed.ULisboa - Research Institute for Medicines, Faculdade de Farmácia, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal., Santos IA; iMed.ULisboa - Research Institute for Medicines, Faculdade de Farmácia, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal; CiiEM - Interdisciplinary Research Center Egas Moniz, Instituto Universitário Egas Moniz, Quinta da Granja, Monte de Caparica, 2829-511 Caparica, Portugal., Fernandes AI; CiiEM - Interdisciplinary Research Center Egas Moniz, Instituto Universitário Egas Moniz, Quinta da Granja, Monte de Caparica, 2829-511 Caparica, Portugal., Pinto JF; iMed.ULisboa - Research Institute for Medicines, Faculdade de Farmácia, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal. Electronic address: jfpinto@ff.ul.pt.
Jazyk:	angličtina
Zdroj:	Journal of pharmaceutical sciences [J Pharm Sci] 2022 Dec; Vol. 111 (12), pp. 3327-3339. Date of Electronic Publication: 2022 Aug 23.
DOI:	10.1016/j.xphs.2022.08.023
Abstrakt:	Co-amorphization is a promising approach to stabilize drugs in the amorphous form. Olanzapine, a poorly water-soluble drug was used in this study. Sulfonic acids (saccharin, cyclamic acid and acesulfame), free and in salt forms, were used as co-formers and compared with carboxylic acids commonly used in the preparation of co-amorphous systems. Several manufacturing techniques were tested, and the co-amorphous systems characterized by differential scanning calorimetry, X-ray powder diffraction, thermogravimetry and Fourier-transform infrared spectroscopy. Free sulfonic acids produced co-amorphous systems with the drug, unlike their salts. Spectroscopy data suggests the formation of salts between olanzapine and the sulfonic acids, used as co-formers. The co-amorphous system produced with saccharin by solvent evaporation, showed the most notable solubility enhancement (145 times). The stability of amorphous and co-amorphous olanzapine systems was assessed upon exposure to stress conditions during storage. Amorphized olanzapine readily reconverted back to the crystalline form while sulfonic acids:olanzapine co-amorphous were stable for up to 24 weeks in low/medium humidity conditions (11-75% RH). Results highlight the potential advantages offered by sulfonic acids as co-formers to produce stable and more soluble co-amorphous olanzapine. Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper (Copyright © 2022 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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