Formulation Development and assessment of solid dispersion and hydrotropy for BCS Class II drug solubility enhancement

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, beta-cyclodextrin. Method: 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, the highest enhancement in solubility is 67 times. While, 37.34 times, 49 times increase in solubility was observed in 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 is 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.