ABSTRACT
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.