In-vitro and In-vivo Characterization of Entacapone Loaded Nanostructured Lipid Carriers Developed by Quality-By-Design Approach

Abstract

Entacapone, a reversible catechol-o-methyl transferase inhibitor, is used to enhance the action of dopamine agonists by reducing their metabolism and the "Wearing-off" effects associated with long-term use in the treatment of Parkinson's disease. It is used as an adjunct to levodopa/Carbidopa therapy. Due to limited dissolution and first-pass clearance, it suffers from low and variable bioavailability. The present study aims to explore the potential of nanostructured lipid carriers(NLCs) for the delivery of Entacapone. The Quality by Design (QbD) approach was used for the systematic development of NLCs. The 23 full factorial design were investigated using Design-Expert®11 software. The three independent variables viz. content of total lipid (X1), surfactant (X2), and sonication time (X3) were optimized against two responses viz. particle size and entrapment efficiency. The optimized NLCs were characterized for their size, surface morphology, entrapment efficiency, drug release, thermal and crystallographic studies. The prepared Entacapone-loaded NLCs were capable of sustaining the release of the drug within therapeutic concentration for a prolonged time. In-vivo pharmacokinetic studies in Entacapone-loaded NLCs showed an increase in t1/2, AUC0-∞, MRT compared to free drug, which confirms the enhancement of bioavailability while the reduction in elimination (Kel) depicts prolonged action of Entacapone by loading in NLCs. The results displayed Entacapone loaded NLCs have promising potential for oral delivery and may enhance the therapeutic effect and thereby reduce the dosing frequency which is a major issue with the present drug.