Fabrication and characterization of mucoadhesive topical nanoformulations of dorzolamide HCl for ocular hypertension

Abstract

The purpose of this study was to prepare chitosan-dextran sulphate and chitosan-sodium tripolyphosphate nanoparticles of Dorzolamide HCl. Dorzolamide HCl is used in higher doses (2–2.2%) topically resulting topical as well as systemic side effects, reducing the dose and making the formulation stay in ocular cavity can reduce the side effects. In the present study mucoadhesive nanoformulations of Dorzolamide HCl have been prepared by Ionotropic gelation mechanism and characterized for different parameters like particle size, zeta potential, drug entrapment, particle morphology; in-vitro drug release, ex-vivo transcorneal permeation and in vivo efficacy. The particles showed sustained in vitro drug release which followed the Higuchi kinetic model and release the drug by a combination of dissolution and diffusion. The formulations, namely DD3 and DS6, having least particle size (182.63 ± 4.64 and 172.3 ± 9.03 nm) and highest zeta potential (43.03 ± 0.51 and 36.46 ± 0.59 mV) were selected for further studies. The particles were spherical and scattered. PXRD and DSC indicated decrease in crystallinity of drug in the nanoparticle formulation. Optimized formulations exhibited excellent transcorneal permeation with no signs of corneal damage (% hydration 75–80%) and found mucoadhesive (93.37 ± 1.86% and 91.59 ± 1.48%) and stable. The in vivo ocular hypotensive activity revealed significantly higher hypotensive activity (p < 0.05) with no signs of ocular irritation. Hence can be considered for the clinical application.