Lacrimal and Plasmatic Kinetics of Morphine After an Ophthalmic Delivery of Three Different Formulations

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The aims of this work were to study the influence of a thermoreversible gel and an insert containing morphine on lacrimal and plasmatic kinetics in comparison with a simple solution. Lacrimal uptake was carried out with a Millipore filter which was characterized by a total recovery of morphine and an absence of inter. ference on the CPG/SM procedure.Contrary to the thermoreversible gel, the inserts prolonged the lacrimal and plasmatic kinetics. In the lacrimal fluid, Cmax was reduced from 21.9 to 4.8 mg/ml and Tmax delayed from 2.9 to 51.4 minutes. Likewise, in the plasma, Cmax was decreased from 116 to 37 ng/ml and Tmax prolonged from 17 to 135 minutes. This plasmatic prolongation was equivalent to the one reported with oral prolonged release devices containing morphine. Moreover, the insert areas under the curve (taking account of the delivered dose) in the lacrimal fluid and in the plasma were multiplied by from 1.6 and 2.6, respectively, in comparison with the solution.