Journal of Advances in Medical and Pharmaceutical Sciences

Aim: The aim of this work was to increase the bioavailability of linagliptin, a BCS class-III drug, by improving permeability. For this purpose, linagliptin loaded different non-ionic surfactant vesicles were formulated and evaluated using statistical optimization.

Methods: Two independent variables selected were surfactant span 60 (X₁), cholesterol (X₂) and three dependent variables were evaluated like percent drug entrapment efficiency (Y₁), percent drug content (Y₂) and percent cumulative drug release (Y₃) respectively. Based on the central composite design of user-defined design, nine batches of non-ionic surfactant vesicles (Niosomes) were prepared by thin film hydration method (TFHM) and modified ether injection method (MEIM) each respectively. The relation between the dependent and independent variables was drawn out from the mathematical equation and response surface methodology (RSM). Statistical analysis was performed using ANOVA.

Results: Microscopic observation confirmed that all particles were uniform in size and shape. Particle size of non-ionic surfactant vesicles measured by SEM was between 10μm to 100μm that given the evidence of large unilamellar vesicles formed by TFHM. In vitro dissolution studies were carried out in phosphate buffer (pH 7.4) for 8 hours according to the USP paddle method. The maximum and minimum drug releases were observed as 85.5% and 79.65% from non-ionic surfactant vesicles respectively, after 8 hours. Release kinetics was studied in different mathematical release models to find out the linear relationship and release rate of the drug. The FTIR studies have been done to confirm no interaction along with drug and polymer. In this experiment, it is difficult to explain the exact mechanism of drug release. But the drug might be released by fickian diffusion as the correlation coefficient (R²) best fitted with zero order and release exponent (n) was less than 0.43.

Conclusion: At last it can be concluded that all in vitro and ex vivo experiments exhibited promising result to treat type II diabetes mellitus with linagliptin loaded non-ionic surfactant vesicles.