Design and evaluation of mucoadhesive in situ liposomal gel for sustained ocular delivery of travoprost using two steps factorial design

Abstract

Travoprost (TRAVO) is a prostaglandin analog used to reduce the intraocular pressure (IOP) for patients suffering from glaucoma and ocular hypertension. The aim of the present study was the development of a novel in situ mucoadhesive ocular liposomal gel to prolong and improve therapeutic efficacy of TRAVO. With this purpose, liposomal formulations were prepared by implementing a full factorial design to study the effect of three factors; type of permeation enhancer (PE), PE concentration and the ratio of lecithin: cholesterol at two levels. The evaluated responses were entrapment efficiency (EE), vesicle size (VS), polydispersibility (PDI) and zeta potential (ZP). L6 (selected liposomal formulation), composed of 20% sodium deoxycholate (Na DOC) and lecithin: cholesterol at 4:1 ratio showed high EE (67.55%), suitable Ps and PDI (74.19 nm and 0.433) and ZP (−75.5 mv). L6 was incorporated in a second 31 × 21 design to study the effect of concentration of gellan gum (at three level) and carbopol 934 (at two levels) to develop in situ mucoadhesive gel. Selected liposomal in situ gel LISG2 (0.25% gellan gum and 0.5% carbopol 934), showed minimum release (18.2%) after 30 min and maximum release after 24 h (72.5%) and achieve maximum viscosity (4445cps) at physiological conditions, mucoadhesive force (0.438 N), with minimum viscosity (124 cps) at normal conditions. Selected LISG2 will be further in vivo evaluated for irritation and pharmacokinetic. TRAVO LISG was non irritant and showed improved bioavailability (higher concentration of TRAVO in aqueous humor) when compared to the marketed product, and showed more prolonged effect compared to liposomal formulation.