Solubility Improvement of Benexate through Salt Formation Using Artificial Sweetener

• Main Authors: Okky Dwichandra Putra, Daiki Umeda, Eriko Fujita, Tamami Haraguchi, Takahiro Uchida, Etsuo Yonemochi, Hidehiro Uekusa
• Format: Article
• Language: English
• Published: MDPI AG 2018-05-01
• Series: Pharmaceutics
• Subjects: benexate; crystal engineering; solubility; dissolution; sweetener
• Online Access: http://www.mdpi.com/1999-4923/10/2/64

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.