gamma-cyclodextrin and Ocular-Hypertension

Forskolin, a diterpene which displays a potent IOP-lowering activity in several animal species, is very poorly water soluble. This characteristic imposes the ocular administration of the drug as a suspension, a type of formulation which may present several preparative and biological disadvantages, such as e.g. difficulty of sterilization and poor bioavailability. The present report is concerned with an investigation on the solubilization of forskolin by some eye-compatible polymeric agents. While beta- and gamma-cyclodextrin were not particularly effective solubilizers, one polyoxyethylene-polyoxypropylene block copolymer (PluronicR F-127) increased 40 times the drug solubility in water (c. 120 mg/100 ml vs. c. 3 mg/100 ml). When tested on rabbits with artificially increased IOP, the Pluronic vehicle prolonged significantly the duration of the hypotensive activity of forskolin with respect to a standard 1.0% suspension of the drug. The potential of these alternative formulations for increasing the ocular bioavailability of forskolin is discussed.

Topics: Administration, Topical; Animals; beta-Cyclodextrins; Colforsin; Cyclodextrins; gamma-Cyclodextrins; Intraocular Pressure; Male; Ocular Hypertension; Poloxalene; Rabbits; Solubility; Solutions