Identification of two different rate-limiting mechanisms controlling the release of NSAIDs from silastic polymeric devices, and possible implications

Two different rate-limiting mechanisms have been found by examining the release characteristics of meclofenamic acid, BW755C.hydrochloride, and diclofenac sodium from silastic polymeric rods into phosphate (0.1 M, pH 7.3) at 37°C. Experiments were performed using rods with initial drug concentrations of 3, 6 and 9% w/w and plots of Q-t and Q-t 1 2 were made (Q, cumulative amount of drug released into solution; t, time). For each of the three loadings of meclofenamic acid, the Q-t 1 2 plot was linear which indicated a matrix controlled release of the drug. With diclofenac sodium, each of the three loadings gave a Q-t plot that was linear thereby indicating a partition controlled release of this drug. For BW755C.HCl, the release of the drug from rods at the two lowest loadings was matrix controlled, but release from rods at the highest loading was partition controlled. The possible implications of these findings are discussed in regard to medicated vaginal devices or intracervical devices.