Purpose. To prepare powder formulations for brain targeting of an antiischemic agent by nasal administration. Methods. The microparticles have been obtained by spray-drying in the presence of mannitol and lecithin, or chitosan as carriers. The drug content was detected by UV-spectrophotometric analysis; morphology by scanning electronic spectroscopy and particle size by laser diffraction. In vitro drug release studies from microspheres were achieved according to USP 24. Ex vivo mucoadhesive tests were performed on sheep nasal mucosa blowing an air stream over the microsppheres spread onto the mucosa and calculating the detection of drug content by HPLC, upon dissolution in water. The permeability of both free and microencapsulated drug was studied onto sheep nasal mucosa using phosphate buffer (pH 6.5) as receptor solution and measuring drug concentrations by HPLC. Male Wistar rats received an intravenous infusion of drug. Its nasal administration was also performed using insufflators Monopowder P® (Valois Dispray, France). After the administrations, blood and liquor samples, the olfactory bulb and ventricular sections of the brain were withdrawn and the related drug amounts analysed by HPLC. Results. The drug influenced the size and morphology of microparticles. The dissolution rate of drug decreased after loading in chitosan microparticles. About 60% of these microspheres was recovered after mucoadhesive tests. The permeation rate of free drug was higher than the encapsulated drug in chitosan microspheres. The drug was not found in the central nervous system (CNS) after intravenous administration, which allowed to obtain blood concentrations in the micromolar range. After nasal administration of the same dose, the drug was found in the CNS (micromolar range in the liquor), but not in the blood. Conclusion. Nasal administration to rats of microparticles obtained by spray-drying can be performed in the aim to obtain the selective CNS targeting of antiischemic drugs.
Nasal administration and brain targeting of an antiischemic agent
DALPIAZ, Alessandro;BORTOLOTTI, Fabrizio;COLOMBO, Gaia;FERRARO, Luca Nicola;TANGANELLI, Sergio;SCATTURIN, Angelo;MENEGATTI, Enea;
2005
Abstract
Purpose. To prepare powder formulations for brain targeting of an antiischemic agent by nasal administration. Methods. The microparticles have been obtained by spray-drying in the presence of mannitol and lecithin, or chitosan as carriers. The drug content was detected by UV-spectrophotometric analysis; morphology by scanning electronic spectroscopy and particle size by laser diffraction. In vitro drug release studies from microspheres were achieved according to USP 24. Ex vivo mucoadhesive tests were performed on sheep nasal mucosa blowing an air stream over the microsppheres spread onto the mucosa and calculating the detection of drug content by HPLC, upon dissolution in water. The permeability of both free and microencapsulated drug was studied onto sheep nasal mucosa using phosphate buffer (pH 6.5) as receptor solution and measuring drug concentrations by HPLC. Male Wistar rats received an intravenous infusion of drug. Its nasal administration was also performed using insufflators Monopowder P® (Valois Dispray, France). After the administrations, blood and liquor samples, the olfactory bulb and ventricular sections of the brain were withdrawn and the related drug amounts analysed by HPLC. Results. The drug influenced the size and morphology of microparticles. The dissolution rate of drug decreased after loading in chitosan microparticles. About 60% of these microspheres was recovered after mucoadhesive tests. The permeation rate of free drug was higher than the encapsulated drug in chitosan microspheres. The drug was not found in the central nervous system (CNS) after intravenous administration, which allowed to obtain blood concentrations in the micromolar range. After nasal administration of the same dose, the drug was found in the CNS (micromolar range in the liquor), but not in the blood. Conclusion. Nasal administration to rats of microparticles obtained by spray-drying can be performed in the aim to obtain the selective CNS targeting of antiischemic drugs.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
