Studies on the effect of pilocarpine incorporation into a submicron emulsion on the stability of the drug and the vehicle.

In order to obtain a novel ocular formulation with a potential for prolonging pilocarpine activity, the drug (2.0%) was incorporated into a submicron emulsion containing soya-bean oil and lecithin as emulgator. The effect of drug incorporation into the emulsion on its physical stability and on the other hand, the potential of the vehicle to reduce drug degradation at pH higher than 5.0 was studied. The pH was adjusted to 6.5 or 5.0 and the physicochemical stability of the formulations was observed. The mean diameter of oily particles in the resulting emulsions measured by a laser diffractometer was 0.6-0.7 micron and this was larger than in a drug-free emulsion where a 0.33 micron value was measured. The formulations were physically stable for 6 months at 4 degrees C, but progressing chemical degradation of pilocarpine was noted at pH 6.5. At that pH nearly 8% of pilocarpine was degraded to isopilocarpine and pilocarpic acid, both in the emulsion and in the solution. Thus, it may be concluded that pilocarpine in submicron emulsion is not protected against degradation. The presence of pilocarpine changes the physical stability of the vehicle since the formulation was easily destabilized during autoclaving or at room temperature. In the presence of higher concentration of lecithin (2.4%) or co-emulgators (poloxamer 2.0% or Tween 80 0.5%) the mean droplet size in the emulsions was the same as in a drug-free system. However the emulsions containing poloxamer were not stable during storage. Viscosity of pilocarpine emulsions can be increased by addition of methylcellulose or sodium carmellose (1.0%), but an intensive creaming occurs in these systems. Pilocarpine base is less suitable for emulsion preparation than hydrochloride salt, and emulsions prepared at pH 5.0 show the most satisfying stability.