Design and In Vitro Evaluation of Atovaquone Nanosuspension Prepared by pH Based and Anti-solvent Based Precipitation Method

Abstract The aim of the research was to design a novel pH based precipitation method for formulation of atovaquone nanosuspension. The study compares efficiency of two bottom-up methods namely, pH and anti-solvent based precipitation to reduce particle size of atovaquone. The anti-solvent precipitation method uses tetrahydrofuran as the solvent with poloxamer and povidone as stabilizers. The pH based precipitation method includes sodium hydroxide as basifying agent in combination with poloxamer as wetting agent, povidone and phospholipids as stabilizing agents and citric acid as the acidifying agent for precipitation. The optimized nanosuspension obtained in the bottom-up step was subjected to microfluidization in the top-down step. It was found that phospholipids helped in improving physical stability of nanosuspension. The water solubility of atovaquone was improved from 0.74 to 11.98 μg/ml in the adsorbed pH based nanosuspension. The particle size of nanosuspension formed using anti-solvent based precipitation was 340 ± 20 nm and the adsorbed nanosuspension had dissolution of 23% in 2 h. Conversely, the particle size of nanosuspension formed using pH based precipitation was 297 ± 10 nm and the adsorbed nanosuspension showed dissolution of around 40% in 2 h. Atovaquone nanosuspension prepared by pH based precipitation method was stable till 6 months.