Development of oral piperaquine nanoparticles: A study on formulation, characterization and in-vivo performance

Piperaquine (PQ) is an anti-malarial bisquinoline BCS Class-II drug having low aqueous solubility and oral bioavailability, which affects its therapeutic effectiveness. Pharmaceutical Nanotechnology has proved its potential to overcome the challenges associated with poorly water-soluble drugs.

The fabrication of Piperaquine nanoparticles (PQ-NPs) through the antisolvent technique with subsequent characterization to improve the dissolution and bioavailability was the primary objective.

PQ-NPs were prepared using anti-solvent precipitation Method. The polymers hydroxypropyl methylcellulose (HPMC) of 0.25%, polyvinylpyrrolidone (PVP-K30) of 0.25 %, and sodium lauryl sulfate (SLS) of 0.5 % were used as stabilizers. The Particle size, PDI, zetapotential, DSC, XRD, SEM, In-vitro dissolution, and in vivo study were performed for characterization of PQ-NPs.

The produced optimized PQ-NPs had a particle size of 184 nm, PDI of 0.248 and zeta potential of -31.4 mV. The NPs had a lower melting point and crystalline content, as shown by differential scanning calorimetry (DSC) and XRD. The SEM analysis confirmed the smaller particle size with a larger surface area. PQ-NPs showed a significantly faster release profile than raw drug, achieving 79.56% drug release in 5 minutes versus 27.31% (p < 0.05). Pharmacokinetic studies in mice revealed that C_max,T_max and AUC were significantly enhanced for PQ-NPs (C_max: 2.753 µg/ml vs. 1.233 µg/ml; T_max: 1.0 ± 0.3 hr vs 1.5 ± 0.3 hr, AUC: 1.119 µg.hr/ml vs. 0.954 µg.hr/ml.

The findings indicate that PQ-NP were successfully fabricated, having substantial improvements in solubility, dissolution rate, and bioavailability, making them a promising approach for enhancing the therapeutic performance.