Document Type : Original Article
Authors
1
Department of Pharmaceutics, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt
2
Ophthalmic Center, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt
Abstract
Ketorolac tromethamine was formulated in different ophthalmic
preparations namely; eye drops, gels, ocuserts and ointments using
the following carriers; sodium carboxymethyl cellulose (sod.
CMC), polyvinyl alcohol (PVA), hydroxypropylmethyl cellulose
(HPMC), absorption base and gelatin. The ophthalmic
formulations were prepared containing 0.5% of the drug. All
prepared formulae containing the drug were subjected to stability
study and release characteristics. Also, the effect of these drug
carriers on the uptake and ocular disposition of ketorolac
tromethamine by the eye tissues of rabbits (conjunctiva, cornea,
iris-ciliary body and aqueous humor) was studied.
The obtained results revealed that, the released amounts from
the ophthalmic preparations after six hours can be arranged in the
following order; Eye drops > ocuserts > gel > ointments. Sod CMC
eye drops exhibited the higher rate of release than sod CMC gel,
PVA and absorption base ointments. Gelatin ocuserts exhibited the
higher rate of release than HPMC ocuserts and carbopol 934 &
sod CMC ocuserts. The release rate of the drug from eye drops and PVA ointment obeys first order kinetics, while, other preparations
obey Higuchi diffusion model with non-Fickian kinetics.
Most formulations (including eye drops) could be stored for 6
months at 25°C, 35°C, 45°C without physical or chemical
degradations of the drug. However, PVA and absorption bases
showed some changes in the drug content (t90 was 2.84 months for
both at 45°C). The decomposition rate of ketorolac tromethamine
followed the first-order degradation kinetic. The highest stable
formulae are, sod CMC eye drops and gel (t90 values were, 151.9
and 91.18 months, respectively at 45°C). The highest concentration
of the drug (Cmax) from all tested formulations is provided in
conjunctiva followed by cornea, iris-ciliary body, then aqueous
humor. The peak time for maximum drug concentration (Tmax)
from sod CMC eye drops was two hours. While, that for sod CMC
gel, PVA ointment and gelatin ocuserts was three hours in all
tissues after the application of the tested formulations. In addition,
the total availability of the drug from the tested formulations was in
the following order: gelatin ocuserts > sod CMC gel > PVA
ointment > sod. CMC eye drops.
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