Development and Optimization of a Dolutegravir Nanosuspension Using Box Behnken Design

Abstract

Objective: This study aimed to develop and optimize a nanosuspension of Dolutegravir, an integrase inhibitor with low aqueous solubility, using the sonoprecipitation technique. The objective was to enhance the drug's solubility and oral bioavailability by preparing nanosuspension. Methods: A box-behnken design was employed to systematically investigate the impact of stabilizer concentration, sonication amplitude, and time on the particle size and polydispersibility of the nanosuspension formulations. Various stabilizers, including Soluplus®, Poloxamer 188, Poly Vinyl Pyrrolidone (PVP) K90, Hydroxy Propyl Methyl Cellulose (HPMC), and Tween 80, were evaluated. Fourier transform infrared spectroscopy confirmed drug-polymer interactions, while differential scanning calorimetry and X-ray diffraction revealed partial amorphization. Scanning electron microscopy confirmed nanoscale particle size and morphology. Results: The optimized formulation (NS6) with 1% Soluplus®, 65 W amplitude, and 10 min sonication exhibited nanoparticles of 75.3 nm with low polydispersity. NS6 demonstrated enhanced drug release compared to the pure drug, attributed to particle size reduction and amorphization. In vitro tests indicated acceptable stability over time and temperature. Conclusion: The application of Box-Behnken design resulted in an optimized nanosuspension formulation capable of improving the oral bioavailability of poorly soluble Dolutegravir. The formulation exhibited favorable characteristics, including reduced particle size, amorphization, and enhanced drug release, highlighting its potential as an effective delivery system for Dolutegravir in Human Immuno Deficiency Virus (HIV) treatment.