Thesis Abstract

Abstract
The use of lipid-based micro suspensions for ophthalmic drug delivery is an emerging area of research that offers significant advantages over traditional formulations. This study focuses on the development of lipid-based micro suspensions for the ophthalmic delivery of gentamicin, a broad-spectrum antibiotic commonly used in the treatment of bacterial infections of the eye. The formulation of lipid-based micro suspensions offers several key benefits for ophthalmic drug delivery. These include improved drug stability, prolonged drug release, enhanced bioavailability, and reduced frequency of administration. Lipid-based formulations also have the potential to overcome the limitations of conventional ophthalmic formulations, such as poor drug solubility and limited corneal penetration. In this study, lipid-based micro suspensions containing gentamicin were prepared using a combination of lipid materials, surfactants, and stabilizers. The formulation parameters were optimized to achieve a uniform particle size distribution and high drug loading efficiency. The physical and chemical stability of the formulations were evaluated over time to ensure long-term efficacy. The in vitro release profile of gentamicin from the lipid-based micro suspensions was studied using a modified Franz diffusion cell system. The results demonstrated sustained release of the drug over an extended period, indicating the potential for reduced dosing frequency in clinical applications. The release kinetics of gentamicin from the lipid-based micro suspensions were analyzed to determine the mechanism of drug release and optimize the formulation for therapeutic efficacy. The ocular tolerability and safety of the lipid-based micro suspensions were assessed in an in vivo rabbit eye irritation test. The results showed that the formulations were well-tolerated and did not cause any significant irritation or adverse effects, indicating their potential for clinical use. Overall, this study demonstrates the feasibility of using lipid-based micro suspensions for the ophthalmic delivery of gentamicin. The developed formulations show promise for improving the therapeutic outcomes of gentamicin treatment for ocular infections. Further research is warranted to evaluate the efficacy and safety of these formulations in clinical trials and to explore their potential for other ophthalmic drugs.

Thesis Overview

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.
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.
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.