Enhancing effect of viscous sodium hyaluronate solution on the rectal absorption of morphine.

Abstract

The effect of the viscosity of sodium hyaluronate solution on the rectal absorption of morphine was determined in rabbits. Hollow-type suppositories containing 10 mg morphine in viscous sodium hyaluronate solution of various mean molecular weights (MWs) were prepared. Rectal absorption of morphine in the sodium hyaluronate solution (MW 2.1 x 10(6) daltons) was dependent on sodium hyaluronate concentrations in the range of 0.1 to 3% (w/v). Bioavailability after rectal administration of morphine in 0.1% sodium hyaluronate solution is consistent with that of morphine solution in the absence of sodium hyaluronate and the sustained-release plasma profile was observed for morphine in 3% sodium hyaluronate solution. Administration of hollow-type suppositories containing 10 mg morphine in 1% sodium hyaluronate solution resulted in the highest bioavailability of approximately 2-fold that after administration of morphine in physiological saline solution. Five kinds of sodium hyaluronate solution with MWs of 2.4 x 10(5), 1.0 x 10(6), 1.8 x 10(6) and 2.1 x 10(6) daltons and respective viscosities of 70, 3.3 x 10(3), 3.2 x 10(6), 5.1 x 10(3) and 5.7 x 10(3) cP (20 degrees C) were examined. Optimal viscosity of the sodium hyaluronate solution was found to enhance rectal morphine absorption. These results indicate that the selection of relevant viscosity of the sodium hyaluronate solution may contribute to the improvement of bioavailability of morphine on rectal administration.