BIOAVAILABILITY AND OCULAR DISPOSITION OF KETOROLAC TROMETHAMINE FROM VARIOUS OPHTHALMIC PREPARATIONS

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Ketorolac tromethamine was formulated in different ophthalmicpreparations namely; eye drops, gels, ocuserts and ointments usingthe following carriers; sodium carboxymethyl cellulose (sod.CMC), polyvinyl alcohol (PVA), hydroxypropylmethyl cellulose(HPMC), absorption base and gelatin. The ophthalmicformulations were prepared containing 0.5% of the drug. Allprepared formulae containing the drug were subjected to stabilitystudy and release characteristics. Also, the effect of these drugcarriers on the uptake and ocular disposition of ketorolactromethamine by the eye tissues of rabbits (conjunctiva, cornea,iris-ciliary body and aqueous humor) was studied.The obtained results revealed that, the released amounts fromthe ophthalmic preparations after six hours can be arranged in thefollowing order; Eye drops > ocuserts > gel > ointments. Sod CMCeye drops exhibited the higher rate of release than sod CMC gel,PVA and absorption base ointments. Gelatin ocuserts exhibited thehigher 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 preparationsobey Higuchi diffusion model with non-Fickian kinetics.Most formulations (including eye drops) could be stored for 6months at 25°C, 35°C, 45°C without physical or chemicaldegradations of the drug. However, PVA and absorption basesshowed some changes in the drug content (t90 was 2.84 months forboth at 45°C). The decomposition rate of ketorolac tromethaminefollowed the first-order degradation kinetic. The highest stableformulae are, sod CMC eye drops and gel (t90 values were, 151.9and 91.18 months, respectively at 45°C). The highest concentrationof the drug (Cmax) from all tested formulations is provided inconjunctiva followed by cornea, iris-ciliary body, then aqueoushumor. The peak time for maximum drug concentration (Tmax)from sod CMC eye drops was two hours. While, that for sod CMCgel, PVA ointment and gelatin ocuserts was three hours in alltissues after the application of the tested formulations. In addition,the total availability of the drug from the tested formulations was inthe following order: gelatin ocuserts > sod CMC gel > PVAointment > sod. CMC eye drops.