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Publication
Sulfonic acid derivatives in the production of stable co-amorphous systems for solubility enhancement
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Advisor(s)
Abstract(s)
"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."
Description
Keywords
Sulfonic acid derivatives Stability Solubility Olanzapine Co-amorphous systems Carboxylic acids
Citation
Nuno F. da Costa, Inês A. Santos, Ana I. Fernandes, João F. Pinto. Sulfonic Acid Derivatives in the Production of Stable Co-Amorphous Systems for Solubility Enhancement. Journal of Pharmaceutical Sciences, 2022, 111(12):3327-3339. DOI: 10.1016/j.xphs.2022.08.023
Publisher
Elsevier