FORMULATION DEVELOPMENT OF LAMOTRIGINE NANOPARTICLE LOADED IN SITU GELS FOR NASAL DELIVERY - IN VITRO, PHARMACOKINETIC AND PHARMACODYNAMIC STUDY

Abstract

Lamotrigine belongs to the class of phenyl triazine and utilized for the epilepsy disorder and neuropathic pain. The aim of the study was to prepare and characterize a novel, nanoparticulate lamotrigine   formulation for nasal administration. In current study, Lamotrigine nanoparticles were developed and incorporated in to in situ gel. Lamotrigine undergoes hepatic first pass metabolism which can be avoided via nasal administration. The Lamotrigine nanoparticles were formulated by modified   ionotropic gelation method and were incorporated   in to in situ gel. The prepared nanoparticles were evaluated for their shape, polydispersity index, particle size, zeta potential, in-vitro drug release pattern and encapsulation efficiency.  LG4 nanoparticle formulation showed spherical shaped nanoparticles with particle size of about 82.16±0.4 nm, zeta potential of 39.4±1.44, and acceptable entrapment efficiency of 84.14±0.18, in vitro release of nanoparticles showed 98.31±1.38 drug release after 12 hours. In situ gels were prepared and the optimized gel was selected for incorporating nanoparticles. Prepared nanoparticulate in situ gel formulations were characterized for in-vitro gelation, gelation temperature, mucoadhesive strength, viscosity and drug release. The release of drug from optimized nanoparticulate in situ gel obeyed Korsmeyer-Peppas model. Stability study revealed that the optimized preparation was more stable at refrigerated conditions (4–8^° C). Pharmacokinetic studies revealed the enhancement of bioavailability in terms of AUC and F, there was 2-fold increase in bioavailability of nanoparticle incorporated in situ gel in comparison with lamotrigine solution. Lamotrigine nanoparticle incorporated in-situ gel revealed potent anticonvulsant activity effect on the Pentylenetetrazol induced seizure model in mice.