Enhanced bioavailability and pharmacokinetics parameters of Enalapril solid self nanoemulsifying oral dispersible tablet: formulation, in vitro and in vivo evaluation

Abstract

Enalapril (EN) is an antihypertensive drug that is sparingly soluble in water with limited oral bioavailability. Successfully prepared self-nanoemulsifying systems (SNES) loaded with EN were developed. The solubility of EN in different oils, surfactants, and cosurfactants was tested. Pseudoternary phase diagrams were developed, and various SNES formulations were prepared and evaluated regarding content uniformity, emulsification time, droplet size (DS), and zeta potential (ZP). The selected system was examined using transmission electron microscopy. Solid Self-Nanoemulsifying Systems (SSNES) were formulated using Avicel® PH101 carrier and Aerosil® 200 adsorbent to form a free-flowing powder. The powder was formulated as an oral disintegrating tablet (ODT) using superdisintegrants and tested for physicochemical properties and stability. Finally, an in vivo pharmacokinetic study in healthy human volunteers was carried out. The composition of the selected SNES was 10% Labrafil®, 60% Tween 80, and 30% Transcutol® HP. It developed with an emulsification time of 21 sec, DP range of 60.16 nm, ZP of 1.17 mV, and spherical-shaped globules. The accelerated stability testing proved that there was no significant difference in physical properties after storage for 3 months. The percentage of relative bioavailability for formula F2 was 112.04%. The results of this study proved that the prepared EN-SSNES ODT represents a novel formulation alternative to the currently marketed tablet.