Development and Characterization of Paliperidone Loaded Nanostructured Lipid Carrier

Abstract:

Background: Paliperidone is indicated for the treatment of schizophrenia. It has an absolute oral bioavailability of about 28% as it is poorly soluble in water and also undergoes hepatic first-pass metabolism. Objectives: The purpose of the present study is to improve the solubility, in vitro bioavailability of paliperidone by formulating nanostructured lipid carrier (NLC). Materials and Methods: High shear homogenization followed by the ultrasonication technique was used for the preparation of NLCs loaded with Paliperidone, and were prepared by varying weight of solid and liquid lipid in different ratios. Lyophilization of the selected NLC was carried out to further improve its stability. Results: Glyceryl monostearate, Linoleic acid, and Tween 80 to Tween 20 (2:1) were selected as solid lipid, liquid lipid, and surfactant correspondingly for the development of NLC. NLC formulation F5 was selected as the best formulation as it exhibited lowest particle size, PDI with stable zeta potential and drug release for 12 hr. Selected NLC F5 was further lyophilized to improve the stability using different cryoprotectants vis-à-vis sucrose, sorbitol and aerosol. Lyophilized NLC showed a slight increase in particle size. DSC and P-XRD study revealed molecular dispersion of paliperidone in lipid matrix. Conclusion: Hence the approach of formulating lyophilized NLC for paliperidone has the potential of improving in-vitro bioavailability.

Keywords: High shear homogenization, Ultrasonication, Lyophilization, Bioavailability, Stability.