Abstract

Background: The current investigation contributes to the development of novel Paliperidone (PPD) co-crystals (CCs) using benzamide (BZ) as a conformer. The CCs were synthesized using the solvent evaporation technique.

Methods: The enhancement in solubility was studied by saturation solubility studies. Structural characterization of CCs was performed by Fourier Transform Infra-Red Spectroscopy (FTIR), powder X-ray diffraction (PXRD), Differential Scanning Calorimetry (DSC), Scanning Electron Microscopy (SEM) and Proton Nuclear Magnetic Resonance (¹H- FT NMR) to verify CC formation.

Results: CCs exhibited a higher aqueous solubility of 2.067±0.004mg/ml when compared to pure drug 0.473±0.012mg/ml. This designated aqueous solubility enhancement of CCs by 4.36 folds. In vitro dissolution data of the CCs exhibited a drug release of 96.5±1.63% in 60min, while pure drug showed a poor release of 37.8±1.76% in the same time period In vivo studies resulted in enhanced rate and extent of drug absorption from CCs when compared to drug suspension.

Conclusion: CCs formed between PPD and BZ present a novel approach in overcoming the hurdles in the solubility of PPD that exhibits poor aqueous solubility.

Keywords: Paliperidone, coformer, bioavailability, solvent evaporation, structural analysis, drug.