Improvement of clonazepam release from a Carbopol hydrogel

The performance of Tween 80, Tween 60, oleic acid, oleyl alcohol and Azone as enhancers of clonazepam permeation from a Carbopol hydrogel through a cellulose nitrate membrane was investigated. The effect of incorporating methyl beta-cyclodextrin (DS 1.8) in combination with clonazepam as a solid phase into some vehicles was also tested. In vitro release studies were carried out with a Sartorius apparatus and the following parameters were evaluated: drug solubility in the vehicle; partition coefficient of the drug between lauryl alcohol (the solvent which impregnates the membrane) and the vehicle; steady state flux; permeability constant; diffusion coefficient; lag time. The release kinetics followed a nearly zero-order pattern, although the diffusion-controlled mechanism might also have been operative. Maximum drug release (2.5 times that of the gel base) was achieved for the formulation containing clonazepam and methyl beta-cyclodextrin in a 1:1 (mol/mol) ratio as a solid phase, in a vehicle composed of water, propylene glycol, Tween 80 and Azone at a mass fraction of 43%, 50%, 2% and 5%, respectively.