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Pharmaceutics 2018, 10(2), 64;

Solubility Improvement of Benexate through Salt Formation Using Artificial Sweetener

School of Pharmacy and Pharmaceutical Sciences, Hoshi University, 2-4-41 Ebara, Shinagawa, Tokyo 142-8501, Japan
Department of Chemistry, Tokyo Institute of Technology, 2-12-1 Ookayama, Meguro, Tokyo 152-8551, Japan
Faculty of Pharmaceutical Sciences, Mukogawa Women’s University, 11-68 Koshien 9-Bancho, Nishinomiya, Hyogo 663-8179, Japan
Current Address: Pharmaceutical Technology and Development, AstraZeneca Gothenburg, Pepparedsleden 1, S-413 38 Mölndal, Sweden.
Authors to whom correspondence should be addressed.
Received: 8 May 2018 / Revised: 23 May 2018 / Accepted: 24 May 2018 / Published: 26 May 2018
(This article belongs to the Special Issue Dissolution Enhancement of Poorly Soluble Drugs)
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Benexate, a drug used clinically as a defensive type anti-ulcer agent, has poor solubility and a bitter taste. To improve its solubility, a crystal engineering approach was proposed with the formation of novel salts using an artificial sweetener as a salt co-former. This was also expected to address the bitter taste of the drug. In this work, we report on the preparation and evaluation of the physicochemical properties of the novel salts benexate saccharinate monohydrate and benexate cyclamate whose crystal structures were determined by single-crystal X-ray structure analysis. These novel salts showed higher solubility and faster dissolution profiles that were associated with the occurrence of local layered-like structures. They also showed better moisture uptake profiles and were classified as non-hygroscopic materials. Therefore, benexate saccharinate monohydrate and benexate cyclamate expedited the development of sweet pharmaceutical salts of benexate with improved performances. View Full-Text
Keywords: benexate; crystal engineering; solubility; dissolution; sweetener benexate; crystal engineering; solubility; dissolution; sweetener

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Dwichandra Putra, O.; Umeda, D.; Fujita, E.; Haraguchi, T.; Uchida, T.; Yonemochi, E.; Uekusa, H. Solubility Improvement of Benexate through Salt Formation Using Artificial Sweetener. Pharmaceutics 2018, 10, 64.

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