Preparation and characterization of dicarboxylic acids salt of aripiprazole with enhanced physicochemical properties. (21st April 2021)

• Record Type: Journal Article
• Authors: Hamideh, Afrooz; Rahman, Ziyaur; Dharani, Sathish; Khuroo, Tahir; Mohamed, Eman M.; Nutan, Mohammad T. H.; Reddy, Indra K.; Khan, Mansoor A.
• Is Part Of: Pharmaceutical development and technology. Volume 26:Number 4(2021)
• Page Start: 455
• Page End: 463
• Publication Date: 2021-04-21
• Subjects: Aripiprazole -- malonic acid -- maleic acid -- succinic acid -- solubility -- pH-solubility -- pH-stability; Drug delivery systems -- Periodicals; Pharmaceutical technology -- Periodicals; Drugs -- Administration -- Research -- Periodicals; Drug Delivery Systems -- Periodicals; Pharmaceutical Preparations -- Periodicals; Technology, Pharmaceutical -- Periodicals; 615
• DOI: 10.1080/10837450.2021.1888978
• Languages: English
• ISSNs: 1083-7450

Abstract

Abstract: The focus of present work was to prepare salt of aripiprazole (APZ) with dicarboxylic acids to improve physicochemical properties the drug. Dicarboxylic acids used in the study were malonic acid, maleic acid and succinic acid. The salts were prepared with solubilization-crystallization method. The salts were characterized for pH-solubility, dissolution, and stabilities. The Fourier infrared spectroscopy, X-ray powder diffraction, differential scanning calorimetry and near infrared chemical imaging indicated formation of new solid phase. pH-solubility profiles of the salts were similar to the drug except higher solubility were observed in the salts at all tested pH. The highest solubility was observed for APZ-Malonate salt among all the prepared salts. The solubility curve was inverted 'V' shape for APZ-maleate and APZ-succinate while it was inverted 'U' shape for APZ-malonate. The water solubility of APZ, APZ-malonate, APZ-maleate and APZ-succinate were 0.07 ± 0.02, 3503.9 ± 37.4, 269.3 ± 6.9 and 729.4 ± 9.4 µg/mL, respectively. The dissolution was 2.9 ± 0.4, 18.4 ± 3.9, 19.5 ± 1.4 and 36.6 ± 4.0% in 45 min for APZ, APZ-maleate, APZ-malonate, and APZ-succinate. The stabilities of the salts were similar to the drug. Thus, salts improved the physicochemical properties of the drug, and have similar stability profiles as that of APZ.