Effect of Aerosil® on the properties of lipid controlled release microparticles

Theophylline-loaded microparticles of a lipid carrier, Precirol(R) ATO 5, were prepared by the ultrasonic spray-congealing method. The goal of the work was to investigate the effect of different concentrations and kind of colloidal silicon dioxide (Aerosil(R) 90, 200 and 300) on the microparticle characteristics (particle size, drug loading, morphology and kinetics of release). The results showed that the introduction of Aerosil(R) improved the drug distribution in the different particle sizes and that the mean diameter of the microparticles decreased with the viscosity of the suspension to be nebulized, especially that with Aerosil(R) 300. Whatever the microparticles formulation is, SEM and image analysis did not reveal any remarkable difference of the microparticle shape and surface area, suggesting that other parameters could influence the dissolution behaviour. Actually, the dissolution profiles of all the formulations appeared to be closely related to the physico-chemical properties of Aerosil(R), especially to its gelation properties, which are a function of its specific surface area. In particular, microparticles having high concentration of Aerosil(R) 200 and 300 approached a zero order release kinetics, while Aerosil(R) 90 microparticles followed a first order release kinetics. Therefore, the drug release rate is controlled by the extent and rate of water absorption/swelling of the Aerosil(R) employed. Finally, DSC, HSM, XRD and FT-IR. evidenced the permanence of the drug in its original state. (C) 2004 Elsevier B.V. All rights reserved.