Bio-Distribution and Pharmacokinetics of Topically Administered γ-Cyclodextrin Based Eye Drops in Rabbits

Area of Science:

• Ophthalmology
• Pharmacology
• Drug Delivery Systems

Background:

• Topical ocular drug delivery faces challenges in achieving therapeutic concentrations in posterior eye tissues.
• Gamma-cyclodextrin (γCD) is explored as a formulation excipient to enhance drug solubility and ocular penetration.

Purpose of the Study:

• To evaluate the ocular pharmacokinetics, bio-distribution, and local tolerability of γCD-based irbesartan 1.5% and candesartan 0.15% eye drops.
• To determine drug concentrations in various ocular tissues and plasma after topical administration in rabbits.

Main Methods:

• A randomized, controlled study involving 59 New Zealand White albino rabbits.
• Single and multiple topical administrations of irbesartan 1.5% and candesartan 0.15% eye drops.
• Quantification of drug concentrations in retinal tissue, vitreous humor, aqueous humor, cornea, and plasma using LC-MS/MS.
• Assessment of local tolerability using modified Draize tests and corneal esthesiometry.

Main Results:

• Both irbesartan and candesartan eye drops were rapidly absorbed and distributed to anterior and posterior ocular tissues.
• Peak retinal concentrations (Cmax) within 0.5h were 251 ± 142 ng/g for irbesartan and 63 ± 39 ng/g for candesartan after single dose.
• Mean retinal concentrations after multiple doses were 338 ± 124 ng/g for irbesartan and 36 ± 10 ng/g for candesartan.
• Favorable local tolerability was observed with no significant differences between treated and control eyes.

Conclusions:

• γCD-based irbesartan and candesartan eye drops effectively deliver pharmacologically relevant concentrations to rabbit retinal tissue.
• The formulations demonstrate favorable safety and tolerability profiles in the rabbit model.
• These findings support the potential of these γCD-based eye drops for treating ocular conditions.