Preparation of 3,4-diaminopyridine microparticles by solvent-evaporation methods

The present study compares two methods of preparation of microparticles of 3,4-diaminopyridine (3,4-DAP) for the treatment for multiple sclerosis and Lambert-Eaton myasthenia syndrome. Poly(F-caprolactone) microparticles were prepared with a solvent-evaporation W/O method. The 3,4-DAP was dispersed in dichloromethane, leading to a suspension. The dispersion and the solidification of the dichloromethane droplets in an aqueous phase have led to microparticles of 55.3 +/- 34.7 mum. The incorporation of the drug by milligram of powder was very low (1.91 mug/mg) and the scanning electron microscopy (SEM) did not show any crystal but marks of dissolved crystals were observed on the polymeric surface. Eudragit(R)RS microspheres containing 3,4-DAP were prepared by a solvent-evaporation technique using light mineral oil as continuous phase. The drug and the polymer were completely dissolved in an acetone solution, used as discontinuous phase. This formulation have led to a higher incorporation of the drug (88.25 mug/mg). The particle size was 91.8 +/- 44.3 mum. The observation, by SEM, shows many crystals on the surface and inside the microparticles. A slow-release of the drug in a phosphate buffer pH 7.4 was observed (50% in 60 min and about 70% in 4 h). (C) 2002 Elsevier Science B.V. All rights reserved.