SYSTEMIC ABSORPTION OF MORPHINE AFTER OCULAR ADMINISTRATION - EVALUATION OF MORPHINE SALT INSERT INVITRO AND INVIVO

This work deals with the systemic absorption of morphine occurring after the administration of a morphine salt insert in the conjunctival cul de sac of New Zealand rabbits. The morphine salt inserts were manufactured using hydroxypropylcellulose (HPC) were prepared via direct compression. The release of drug was found to be mostly a diffusion-controlled process and was observed to increase in rate when HPC of lower molecular weight was employed. In vivo release was also due to diffusion of drug molecules through the matrix but was significantly retarded as compared to the in vitro rate (6.45 vs 4.25% min-0.5). In contrast, hydration of the insert was observed to take place at a similar rate under both in vitro and in vivo conditions, and therefore does not appear to be the limiting factor in the release processes. The time course determined for the plasma concentrations resulting from the use of morphine hydrochloride-HPC inserts (25 :75 wt%, 15 mg) was of longer duration than that in the case of a morphine acetate solution and the area beneath the curves was greater with the inserts. © 1990.