Prolonged pulse-entry of pilocarpine with a soluble drug insert

Apparent biophase availability of pilocarpine was studied in the eyes of albino rabbits. Pilocarpine doses of 0.85 and 2.30 mg in aqueous solutions, 1.00 mg in oil and 0.85 mg in a solid insert, were applied ocularly. The insert was a water soluble polyvinylpyrrolidone (PVP) matrix, which released 80% of its pilocarpine content in 35 min in vitro. In the inferior fornix of the eye this insert gelled in about 5 min and dissolved in 1 h. Pupillary diameters were measured and converted to values for the response parameter (RP). Time delay and magnitude of peak response, apparent biophasic availability (area under the curve of RP vs time), and a constant for the apparent rate of elimination were calculated from RP values. The time delay for the peak response was 16.l3-24.0 min, and the constant for apparent rate of elimination was 0.69-0.81 h-1. Neither time delay nor this constant was affected by the dose or the dosage form. Magnitude of the peak response and apparent biophasic availability were influenced by the vehicle and the dose: insert (0.85 mg) greater than oily solution (1.00 mg) greater than aqueous solution (2.30 mg) greater than aqueous solution (0.85 mg). The insert and oily solution did not show vehicle-controlled drug absorption and can be regarded as prolonged pulse-entry medication.