ABSTRACT
This study was carried out on the development of lipid based micro suspension for ophthalmic delivery of gentamicin. The bioavailability of drugs from conventional eye drops is generally low. Many studies have shown that new and more complex ophthalmic drug forms have advantages over conventional ones and can increase the bioavailability of the active ingredient by, among other things, reducing the susceptibility of drug forms to the defense mechanisms of the human eye and increasing the contact time of drugs with the cornea, increasing penetration by the complex anatomical structure of the eye and providing a controlled release of drugs into the eye tissue, which can reduce the frequency of drug use. In this study, lipid-based microsuspensions of gentamicin were developed and investigated as an alternative to the 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 μm. 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 delivery of gentamicin.
CHAPTER ONE
INTRODUCTION AND LITERATURE REVIEW
1.1 General introduction
Topical drops are the most preferred dosage form for treating diseases of the anterior segment of the eye. Eye drops make up 90% of the formulations marketed. The reason can be traced back to the ease of administration and compliance with patient regulations (1, 2). Even so, the bioavailability of drugs topically applied as eye drops in the eye is very poor. Numerous protective mechanisms and structural restrictions pose a challenge and hinder the absorption of drugs by the eye (3). The protective mechanisms include tear formation, blinking, nasolachrymal drainage, while the structural constraints include a small absorbent surface area of ​​the cornea, lipophilicity of the corneal epithelium, metabolism, enzymolysis and binding of the drug to proteins contained in tear fluid (4, 5). Therefore, less than 5% of the topically applied dose reaches the intraocular tissue (6).
In order to overcome the barriers to drug delivery to the eye and improve the bio availability of the eye, various conventional and novel drug delivery systems have been developed. Many studies have shown that new and more complex ophthalmic drug forms have advantages over traditional ones and can increase the bioavailability of the drug through various mechanisms, including reducing the vulnerability of drug forms to the defense mechanisms of the human eye and increasing penetration through the complex anatomical structure of the eye , Extending the contact time of the drug with the cornea and providing a controlled release of drugs into the eye tissue.Â
