Inlfuence of high-viscosity vehicles on miotic effect of pilocarpine.

Gel formulations containing 2% pilocarpine hydrochloride were prepared from ethylene maleic anhydride, carbomer, hydroxyethylcellulose, polyacrylamide, ethylhydroxyethylcellulose, hydroxypropylcellulose, and poly(methylvinyl ether--maleic anhydride). The viscosity characteristics of each formulation were evaluated from rheograms developed at 37 degrees using a cone and plate viscometer. Single-point viscosities were determined at room temperature using a single-point rotational viscometer. Plastic viscosity parameters correlated to miosis durations in the rabbit following ophthalmic dosing of 50 microliters. Carbomer formulations varying in concentration between 0.9 and 5.0% (w/w) showed a discontinuous relationship when either yield value or plastic viscosity was plotted against miosis durations. At carbomer concentrations above 3%, miosis durations increased 1.5-fold. Above and below this range, plastic parameters did not correlate to miosis duration. It was reasoned that the increased duration was a consequence of the gel's increased yield value such that appreciable in vivo thinning of the gel does not take place with eyelid and/or eyeball movements. As a result, the residence time of the drug in the eye would be expected to increase, thus promoting an increased duration.