Development of lipid-based micro suspensions for ophthalmic delivery of gentaamicin

Project Abstract

The development of lipid-based micro suspensions for ophthalmic delivery of gentamicin is a crucial area of research in the field of pharmaceutical technology. Gentamicin, an aminoglycoside antibiotic, is commonly used in the treatment of ocular infections. However, its poor ocular bioavailability and short residence time on the corneal surface limit its therapeutic efficacy. Lipid-based micro suspensions offer a promising solution to these challenges by improving drug solubility, stability, and sustained release in the ocular tissues. In this study, lipid-based micro suspensions were prepared using a combination of phospholipids, surfactants, and stabilizers to encapsulate gentamicin. The formulation parameters were optimized to achieve a uniform particle size distribution, high drug loading efficiency, and enhanced stability. Various characterization techniques such as dynamic light scattering, transmission electron microscopy, and zeta potential analysis were employed to evaluate the physicochemical properties of the micro suspensions. The in vitro release studies demonstrated sustained drug release from the lipid-based micro suspensions over an extended period, indicating their potential for prolonged therapeutic effect in the eye. Furthermore, the cytotoxicity studies conducted on human corneal epithelial cells revealed the biocompatibility of the formulations, suggesting their safety for ocular administration. In vivo pharmacokinetic studies in rabbit models showed enhanced ocular absorption and prolonged residence time of gentamicin from the lipid-based micro suspensions compared to the conventional eye drops. The improved bioavailability of gentamicin in the ocular tissues highlights the efficacy of the micro suspensions as a promising delivery system for ocular infections. Overall, the development of lipid-based micro suspensions for ophthalmic delivery of gentamicin represents a significant advancement in ocular drug delivery technology. The formulation provides a platform for enhancing the therapeutic outcomes of gentamicin by overcoming its limitations in ocular administration. Future studies focusing on optimizing the formulation parameters, exploring different drug combinations, and conducting clinical trials are warranted to further establish the clinical utility of lipid-based micro suspensions in the treatment of ocular infections.

Project Overview

<p> The bioavailability of drugs from conventional eye drops is generally low. Many studies have demonstrated that new and more complex ophthalmic drug forms exhibit advantage over traditional ones and are able to increase the bioavailability of the active substance by, among others, reducing the susceptibility of drug forms to defense mechanisms of the human eye, extending contact time of drug with the cornea, increasing the penetration through the complex anatomical structure of the eye, and providing controlled release of drugs into the eye tissues, which allows reducing the drug application frequency. In this study, lipid-based microsuspensions of gentamicin were developed and investigated as alternative for ophthalmic delivery of gentamicin.<br>Lipid matrices used were prepared by fusion using 1:1, 1:2 and 2:1 mixtures of Phospholipon ? 90G and Softisan ? 154. Gentamicin (0.1, 0.3, 0.5 and 0.7 w/w %) was incorporated into the lipid matrices and microsuspensions were formulated by melt homogenization technique. The microsuspensions for topical ophthalmic delivery were characterized in terms of particle size and morphology, thermal analysis, osmolarity, entrapment efficiency and loading capacity. The in vitro release study of gentamicin in phosphate buffer (pH 7.4) was carried out using polycarbonate dialysis membrane (MWCO 6000-8000) while the ex vivo permeation studies were conducted using excised pig cornea. The permeability coefficient and flux of the formulation across the excised cornea were determined.<br>The particle size of the formulations ranged from 9.15 ? 1.04 to 12.91 ? 0.5 ?m. The microsuspensions had entrapment efficiency range of 25 -64%, which were dependent on the concentration of drug. The osmolarity of the formulation was within the range of 280.33 ? 3.05 -321.67 ? 2.08 mOsmol. The formulations were stable within the period of study. The lipid based formulations exhibited 49 -88% drug release in vitro at 12 h and the release was dependent on the ratio of the lipids used. There was sustained permeability of the formulations through the excised cornea when compared with commercial gentamicin eye drop. The lipid based microsuspensions could be used for ophthalmic. <br></p>