title: Preparation of 3,4-diaminopyridine microparticles by solvent-evaporation methods.
abstract: 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( epsilon -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 microm. The incorporation of the drug by milligram of powder was very low (1.91 micrograms/mg) and the scanning electron microscopy (SEM) did not show any crystal but marks of dissolved crystals were observed on the polymeric surface. EudragitRS 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 micrograms/mg). The particle size was 91.8+/-44.3 microm. 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).
authors.affiliation: Laboratoire de Pharmacie Clinique, UPRES EA 2399, Faculté de Pharmacie, 5, rue Albert Lebrun, 54000, Nancy, France. stephane.gibaud@pharma.u-nancy.fr
authors.forename: Stéphane
authors.initials: S
authors.lastname: Gibaud
authors.forename: Aurélie
authors.initials: A
authors.lastname: Bonneville
authors.forename: Alain
authors.initials: A
authors.lastname: Astier
mesh_terms: D015761:4-Aminopyridine / Q000008:administration & dosage* / Q000031:analogs & derivatives / Q000737:chemistry; D000180:Acrylic Resins; D000077770:Amifampridine; D003692:Delayed-Action Preparations; D004339:Drug Compounding / Q000379:methods*; D005079:Excipients; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D010316:Particle Size; D011091:Polyesters; D012997:Solvents
chemical_list: D000180:Acrylic Resins; D003692:Delayed-Action Preparations; D005079:Excipients; D011091:Polyesters; D012997:Solvents; C016240:polycaprolactone; C050528:Eudragit RS; D015761:4-Aminopyridine; D000077770:Amifampridine