Dose identification of triamcinolone acetonide for noninvasive pre-corneal administration in the treatment of posterior uveitis using a rapid, sensitive HPLC method with photodiode-array detector.

ABSTRACT

Triamcinolone acetonide (TAA) is the drug of choice in the management of ocular inflammations due to its anti-inflammatory and immuno-suppressant activity. Available marketed formulations (Triesence, Trivaris, Kenalog) are in the suspension form recommended to be administered via intravitreal injection, which has many major complications. In the present study, we have designed and evaluated Hydroxypropyl-ß-cyclodextrin (HP-ß-CD),) based conventional formulations of TAA (aqueous suspensions) with different dose strengths to identify the dose strength required for achieving the effective concentrations in vitreous humor following pre-corneal administration of the formulations. Ocular pharmacokinetic studies of conventional formulations of triamcinolone acetonide (TAA) with different dose strengths (1 mg/30µL, 2 mg/30µL, 4 mg/30µL) were performed to identify the dose strength required to produce effective concentrations of TAA in the aqueous and vitreous humor. A rapid, sensitive, selective, accurate and precise bioanalytical method utilizing a small sampling volume (<45 µL) was developed and validated for quantification of TAA in the samples obtained from the ocular pharmacokinetic studies. Aqueous suspensions of TAA with 20% HP-ß-CD produced time course profiles in the aqueous humor at all the dose strengths. However, measurable concentrations and time course of TAA in vitreous humor were achieved only with 4 mg/30µL dose strength.