Enhanced Oral Bioavailability of Etodolac by the Liquisolid Compact Technique: Optimisation, In-Vitro and In-Vivo Evaluation

Abstract

Background: Poor dissolution of Etodolac is one of the major challenges in achieving the desired therapeutic effect in oral therapy. Objective: This study aimed to assess the potential of liquisolid compact technique in increasing the rate of dissolution of Etodolac and thus its bioavailability. Methods: Liquisolid compacts were prepared using PEG 400, Avicel PH-200 and Aerosil 200 as non-volatile liquid, carrier and coating material respectively. Optimisation was carried out by applying a 32 full factorial design using Design expert software 11.0.3.0 to examine the effects of independent variables (load factor and carrier: coating ratio) on dependent variables (angle of repose and % cumulative drug release at 30 min [Q 30 min]).Assessment of bioavailability was based on pharmacokinetic study in rabbits and pharmacodynamics evaluation in rats respectively. Results: The formulation M3 was identified as the optimised formulation based on the better flow (lower angle of repose) and a higher rate of dissolution (Q 30 min >95%). The higher dissolution rate could be due to conversion of Etodolac into an amorphous molecularly dispersed state, availability of larger surface area, enhancement of aqueous solubility and enhanced wetting of drug particles. Studies with DSC, XRD, and SEM verified the transformation of Etodolac from crystalline to amorphous state, a key factor responsible for improving the dissolution rate. Pharmacokinetic profile of M3 was prominent, demonstrating higher absorption of Etodolac in comparison of oral suspension and immediate-release conventional tablets in rabbits. Liquisolid formulation exhibited 27% increment in paw thickness as compared to 57% and 46% increments for oral suspension and immediate-release conventional tablets respectively, after 7 hrs in carrageenan-induced paw model in rats. Conclusion: The results indicated liquisolid compact technique to be a promising strategy to enhance the bioavailability of Etodolac.

Development of Liquisolid Compacts: An Approach for Dissolution Enhancement of Poorly Aqueous Soluble Drugs

“…The external surface morphology of the LSCs were studied using a scanning electron microscope (Hitachi TM 1000, Tokyo, Japan). The samples were first adhered to aluminum stubs, gold-coated sputter with double sided conductive tape of 12 mm diameter, and examined in the scanning microscope [27].…”