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Salt Engineering of Aripiprazole with Polycarboxylic Acids to Improve Physicochemical Properties

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Abstract

Aripiprazole (APZ) has poor physicochemical properties and bitter taste. The current study aimed to prepare salts of APZ with polycarboxylic acids (citric, malic, and tartaric acids) to improve physicochemical properties and impart sour taste to the drug. The salts were prepared by solubilization-crystallization method, and characterized by electron microscopic, spectroscopic, diffractometry, and thermal methods. The salts were assessed for pH solubility, pH-stability, dissolution, and solid-state stability. Fourier transformed infrared, X-ray powder diffraction, and differential scanning calorimetry data indicated formation of new solid phases. APZ and the salts exhibited pH-dependent solubility. The pH solubility curve shape was inverted “V,” inverted “W,” and inverted “U” for APZ, APZ-Citrate, and APZ-Malate and APZ-Tartrate, respectively. Compared to APZ, the solubility of salts at pH 4, 5, and 6 was 3.6–7.1, 23.9–31.5, and 143.4–373.3 folds of APZ. Increase in solubility in water by citrate, malate, and tartrate salts was 5562.8, 21,284.7, and 22,846.7 folds of APZ. The salt formation also leads to an increase in rate and extent of dissolution. The dissolution extent was 3.5 ± 0.5, 71.3 ± 1.2, 80.1 ± 6.2, and 86.1 ± 1.1% for APZ, APZ-Citrate, APZ-Malate, and APZ-Tartrate, respectively. Liquid and solid-state stabilities of the salts were comparable to APZ. In conclusion, salts of APZ with polycarboxylic acids improved solubility, and dissolution, and impart sour taste, which may improve palatability of the drug.

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Authors and Affiliations

  1. Irma Lerma Rangel College of Pharmacy, Texas A&M Health Science Center, Texas A&M University, Reynolds Medical Building, Suite 310, College Station, Texas, 77843-1114, USA

    Hamideh Afrooz, Eman M. Mohamed, Sogra F. Barakh Ali, Sathish Dharani, Mansoor A. Khan & Ziyaur Rahman

  2. Department of Pharmaceutics, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, 62514, Egypt

    Eman M. Mohamed

  3. Irma Lerma Rangel College of Pharmacy, Texas A&M Health Science Center, Texas A&M University, Kingsville, Texas, 78363, USA

    Mohammad T. H. Nutan

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  1. Hamideh Afrooz
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Afrooz, H., Mohamed, E.M., Barakh Ali, S.F. et al. Salt Engineering of Aripiprazole with Polycarboxylic Acids to Improve Physicochemical Properties. AAPS PharmSciTech 22, 31 (2021). https://doi.org/10.1208/s12249-020-01875-x

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