Biopharmaceutical distribution and pharmacodynamic evaluation of intra nasal in-situ gel of Lamotrigine for brain targeted drug delivery

Abstract

Background: The present research investigates the nasal delivery of Lamotrigine by incorporating it into a natural in-situ gelling system. Additionally, the retention of the drug in the nasal cavity was enhanced by employing the natural mucoadhesive polymer locust bean gum (LBG). A preliminary investigation was conducted to determine the optimal concentration of gellan gum. The dosage of the drug was calculated using the Robinson Erikson equation. The central composite design was utilized to optimize the influence of individual variables such as gellan gum and locust bean gum on various responses, including gelation time, gel viscosity, mucoadhesive strength, and the time taken for the drug to release half of its initial concentration (t50). The goal of the current study was to evaluate the in-vivo effectiveness of intra nasal in-situ gel of Lamotrigine. Methodology: The pharmacokinetic and tissue distribution studies were carried out to evaluate the brain targeting efficiency of lamotrigine. Blood samples and tissues of various vital organs like brain, liver, kidneys and heart were obtained at different time intervals, plasma and tissue concentration of Lamotrigine was estimated by reverse phase HPLC. Results: According to the pharmacokinetic analysis, Cmax and AUC0-α is found to be significantly more (P<0.05) for nasal route compared to oral route. In comparison to the oral route, Cmax and AUC0-α was 7 and 6.5 folds more for IN route. The absolute bioavailability was found to be 159.07%. with regard to the oral group, minimal drug was present in any of the other tissue samples. In the pharmacodynamic data also the formulation through nasal route showed a significant difference compared to oral route (pure drug suspension) delivery in PTZ induced study. Keywords: Lamotrigine, in-vivo study, tissue distribution, pharmacodynamics