Design and preparation of novel domperidone loaded polymeric blend electrospun nanofibers for improved oral pharmacodynamic activity

Abstract

Domperidone (DOM) is a BCS class II drug which widely used as an oral medication for the control of nausea and vomiting. It showed a very low and variable bioavailability related to its very poor solubility and pre-systemic metabolism. Polymeric nanofibers (PNFs) exhibit unique properties that make them a favorable choice for drug delivery applications. The study aimed to develop an optimum fast-dissolving oral polymeric electrospun nanofiber of DOM using Eudragit L100/Polyvinyl alcohol (EL-100/PVA) polymer blend. The fabrication process was optimized through a set of formulation parameters (composition of the polymer blend, polymer blend concentration, and electrospinning voltage). The DOM-loaded EL-100/PVA NFs were characterized for surface shape, nanosize, % drug loading, DOM in vitro release, drug/polymer interaction, and in vivo prokinetic study. The optimization process showed defect-free DOM-loaded NFs with very low nano diameter, high DOM loading, and superior in vitro dissolution of DOM at intestinal pH (about 90% of the drug released within 5 min). The drug/polymer interaction study demonstrated the conversion of DOM into an amorphous form, which facilitated its dissolution. No physicochemical interaction between DOM and the polymer blend was observed. In vivo prokinetic study signified the orally enhanced prokinetic activity of DOM-loaded NF relative to pure DOM and commercial DOM product. The DOM-loaded EL-100/PVA NFs exhibited a better effect on the gastrointestinal reactivity relative to free DOM and commercial DOM product. The superior in vitro dissolution and in vivo prokinetic activity proved the promising potential of polymeric NFs to improve the oral delivery of DOM. The optimized DOM-loaded EL-100/PVA NFs may allow for dose reduction and low cardiovascular risk compared to conventional DOM tablets.