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Effect of Counterions on Physicochemical Properties of Prazosin Salts

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ABSTRACT

This study evaluated the effect of counterions on the physicochemical properties of prazosin salts. Salt forms of prazosin, namely, mesylate, besylate, tosylate, camsylate, oxalate, and maleate, were prepared and compared with the marketed anhydrous and polyhydrate forms of prazosin hydrochloride. Physicochemical characterization was performed in the order of crystallinity, hygroscopicity, solubility, and stability to select the optimal salt(s). Permeability study in Caco-2 cell lines and in vivo bioavailability study in rat model were investigated to ascertain their biopharmaceutical advantage. All salt forms were crystalline, nonhygroscopic (except the anhydrous hydrochloride salt), and had solubility in the range of 0.2 to 1.6 mg/ml. All salts were physically and chemically stable at 40°C/75% relative humidity, but degraded in UV-visible light, except the anhydrous hydrochloride salt. Prazosin mesylate was selected as the optimal salt, as it possessed higher solubility, permeability, and bioavailability, compared to the commercial hydrochloride salts. Hydrochloride salt is reported to have poor bioavailability that is partially attributed to its low solubility and extensive common-ion effect in the gastric region. Factors like hydrophilicity of the counterion, hydration state of the salt, and melting point of the salt contribute to the physicochemical properties of the salts. This study has implications in the selection of an optimal salt form for prazosin, which is suitable for further development.

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ACKNOWLEDGMENTS

Lokesh Kumar acknowledges the Department of Science and Technology of the Government of India and the Ranbaxy Science Foundation for providing the research fellowship to carry out this work. Services provided by the Central Instrumentation Laboratory at NIPER Mohali are also gratefully acknowledged.

Declaration of Interest

The authors report no conflict of interest. The authors alone are responsible for the content and writing of the paper.

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Authors and Affiliations

  1. Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Sector-67, Phase-X, S.A.S. Nagar, Punjab, 160062, India

    Lokesh Kumar, Yogesh B. Pawar, Banrida Wahlang & Arvind K. Bansal

  2. Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Sector-67, Phase-X, S.A.S. Nagar, Punjab, 160062, India

    Chhuttan Lal Meena & Rahul Jain

  3. Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Sector-67, Phase-X, S.A.S. Nagar, Punjab, 160062, India

    Kulbhushan Tikoo

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  1. Lokesh Kumar
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  2. Chhuttan Lal Meena
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  7. Arvind K. Bansal
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Correspondence to Arvind K. Bansal.

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Kumar, L., Meena, C.L., Pawar, Y.B. et al. Effect of Counterions on Physicochemical Properties of Prazosin Salts. AAPS PharmSciTech 14, 141–150 (2013). https://doi.org/10.1208/s12249-012-9889-x

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  • DOI: https://doi.org/10.1208/s12249-012-9889-x

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