Uptake and release of budesonide from mucoadhesive, pH-sensitive copolymers and their application to nasal delivery

Microparticles of novel, bioadhesive graft copolymers of polymethacrylic ac id and polyethylene glycol (P(MAA-g-EG)) were prepared. The aims of this st udy were to investigate the uptake and release kinetics of budesonide from P(MAA-g-EG) in vitro as well as the pharmacokinetics following nasal admini stration of the polymer contained budesonide. The loading of budesonide int o the pH-sensitive polymers was examined using various ethanol solutions. E thanol was required for drug solubilization but hindered hydrogel swelling at pH 7.2. Maximum loading of the drug in the polymer was obtained using 25 % ethanol solutions. The release of budesonide from the polymer swollen in 25% ethanol solutions obeyed classical Fickian release behavior after an in itial rapid drug burst. For nasal administration of budesonide-containing P (MAA-g-EG) the plasma concentration of budesonide was kept constant followi ng a peak concentration of the drug approximately 45 min after administrati on. (C) 1999 Elsevier Science B.V. All rights reserved.