Gamma scintigraphic comparison of eyedrops containing pilocarpine in healthy volunteers

The aim of the present study was to compare, in healthy human volunteers (male and female), the corneal contact time of various formulations, each containing one viscosity enhancer from the following list: a phase-transition system (gellan gum, Gelrite), a heteropolysaccharide (xanthan gum) and currently used polymers hydroxyethylcellulose, hydroxypropylmethylcellulose, or poly(vinyl alcohol). These different solutions were compared to a reference solution containing no viscosity enhancers. The corneal contact time of the formulations was evaluated over more than 20 minutes by gamma scintigraphy using Technetium-99m (Tc-99m DTPA) as a radioactive label. An eyedrop containing pilocarpine salts (25 microliters) was instilled in one eye only. Each volunteer received 4 formulations, the interval between the instillations being one week. The protocol has been approved by the relevant institutional human experimentation committee. One minute after instillation, only 23% of the reference solution remained on the ocular surface, whereas the novel formulations maintained, respectively, 77% (xanthan gum) or 82% (Gelrite) of the tracer on the ocular surface. Twenty-one min after instillation, 12% (reference solution), 25% (xanthan gum solution), and 39% (gelrite solution) of the tracer remained on the ocular surface. The results confirm that an increase in viscosity of the formulation (xanthan) delays the clearance of the instilled solution by the tear flow. The effect of the gelation mechanism is superior, especially at the later time points. In this respect, xanthan gum and, particularly, Gelrite are suitable vehicles for ophthalmic drugs.