Influence of drug loading on coated beads release using air suspension technique

Spherical granules were prepared by loading a drug such as Indobufen on 40-45 mesh non-pareil seeds using air suspension coating technique (Wurster process, Uniglatt). The drug was added by spraying a formulated aqueous dispersion onto inert granules in different amounts employing two drug particle sizes with different surface areas. Then all active beads were coated with different thicknesses of polymeric film using the same fluid bed employed for loading the drug. The coatings were applied from aqueous dispersions (pseudolatex) of ethyl cellulose (Aquacoat ECD-30). In this system the drug diffusion is governed by the intrinsic pore network of the membrane. The finest drug particle size gave the fastest drug release rates. Moreover, the lowest drug loadings on inert granules resulted in the slowest drug release. Nevertheless thicker film coats involved a delay of drug release. Further preparations were made to evaluate the influence of changing the seed size to 25-30 mesh, loading the same amount of the drug and obtaining the increased surface are of the individual bead. In order to improve the drug release profile, the effect of changing diethylphthalate to the more water-soluble triethylcitrate and the addition of hydroxypropylmethyl cellulose or polysorbate 80 were also evaluated. In this case the drug diffusion is controlled by dissolution of a part of membrane leaving small channels of polymer coating.