Exploring the Bottom-up and Top-down Techniques of Nanosuspension for Enhanced Solubility and Drug Loading of Atovaquone

Year 2025, Volume: 55 Issue: 3, 390 - 403, 14.01.2026

Karishma Patil , Rushikesh Ghongane , Tejas Nakte Harsha Kathpalia

https://doi.org/10.26650/IstanbulJPharm.2025.1570740

https://izlik.org/JA43AS33GF

Abstract

Background and Aims: Atovaquone is a Class II drug under the Biopharmaceutical Classification System. It is one of the most commonly used drugs to treat pneumonia and malaria. It shows anti-protozoal and anti-pneumocystic activity, but its low water solubility results in poor bioavailability. This research aimed to prepare and analyse atovaquone nanosuspension using a combination of bottom-up and top-down techniques.

Methods: The study explored the efficiency of two bottom-up methods, namely, pH-based and antisolvent- based precipitation, to achieve high drug loading in the nanosuspension. Tetrahydrofuran was used as the solvent to dissolve atovaquone in the presence of sodium hydroxide and povidone as solubilizers. The poloxamer was used as the wetting agent, and Phospholipon 90H as the stabilising agent. Citric acid was used as the acidifying agent for the precipitation.

Results: High-pressure homogenisation in the top-down step after precipitation produced particles with a size of 195.2 nm. The nanosuspension showed 6% drug loading. The formulation was freeze-dried to improve stability and restrict crystal growth, resulting in a particle size of 343±20 nm. The aqueous solubility of atovaquone in the nanosuspension was 13 times higher, and the dissolution rate was increased by seven-fold compared with the unprocessed drug. The atovaquone nanosuspension prepared by this combination method was stable for 3 months.

Conclusion: The study successfully demonstrated the potential of combination methods to obtain a nanosuspension with high drug loading and small particle size.

Keywords

pH-based precipitation , Anti-solvent-based precipitation , High-pressure homogenisation , Top-down method , Bottom-up method

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