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Letters in Drug Design & Discovery

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ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

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Research Article

Formulation Development and Assessment of Solid Dispersion and Hydrotropy for BCS Class II Drug Solubility Enhancement

Author(s): Neha Bajwa, Mela Singh, Srishti Naryal, Shipra Mahal, Sumit Mehta, Jitender Madan and Ashish Baldi*

Volume 21, Issue 2, 2024

Published on: 12 October, 2022

Page: [305 - 319] Pages: 15

DOI: 10.2174/1570180819666220822115049

Price: $65

Abstract

Aim: This study aimed to evaluate the potential of different hydrophilic polymers to increase Arteether's water solubility.

Background: Arteether is classified as a class II biopharmaceutical in the Biopharmaceutical Classification System (BCS), with low water solubility (17 g/mL) and dissolution rate, resulting in poor bioavailability.

Objective: The goal of this research is to improve the water solubility of Arteether (ART) by using a solid dispersion and hydrotropic approach with a variety of carriers, such as PEG-6000 PVP K-30, Poloxamer- 188, Poloxamer-407, HPMC E 15LV, HPMC K-100M, sucrose, and mannitol, sodium benzoate, sodium citrate, Urea, nicotinamide, and beta-cyclodextrin.

Methods: Melting and evaporation methods were used to make the solid dispersion. Instrumental examinations, including XRD, DSC, FTIR, and SEM, confirmed any physical changes caused by the interaction of ART and carriers.

Results: The most significant increase in water solubility of Arteether was discovered with CD: PEG600:Pol -407, and the highest enhancement in solubility was 67 times. While 37.34 times and 49 times increase in solubility was observed at 1:4.3:3.7 weight ratio of AE: PEG-6000:Poloxamer-407 40 percent mix of nicotinamide, respectively. The in vitro results show that ART's dissolution rate in the solid dispersion system was dramatically reduced compared to pure drug. This might be because of the drug's enhanced wettability, dispersion ability, and transition from crystalline to amorphous form. Compared to the ART itself, the permeability of Arteether from solid dispersion was increased up to 7 times. However, the permeability of solid cyclodextrin dispersion was extremely low, just 4.42 times. This may be due to the drug encapsulation in the cyclodextrin cavity.

Conclusion: This research successfully developed and optimized various polymer and solubility enhancement approaches for Arteether, resulting in increased water solubility, which may improve Arteether's oral bioavailability. The findings of this study might be utilized to develop an oral dosage of Arteether with enhanced bioavailability.

Keywords: Bioavailability, Cyclodextrin, Dissolution, Hydrotropy, Permeability, Solid dispersion

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