Effect of hydrophobicity of a drug on its release from hydrogels with different topological structures

The effect of the topological structure; that is, the network heterogeneity , of hydrophobically modified, slightly acidic hydrogels on the binding and release of low molar mass drugs has been studied using ibuprofen and ephed rine as model compounds with varying water solubility. The difference in th e heterogeneity of the gels has been produced by the choice of the hydropho be copolymerized into the polymer network. The effect of the drug loading o n the release kinetics has been investigated as well. The release of hydrop hobic ibuprofen was slower from a strongly aggregated heterogeneous gel tha n from a more homogeneous one, because of the strong hydrophobic interactio n between ibuprofen and the heterogeneous hydrogel. The release of hydrophi lic ephedrine from the homogeneous gel with an initial drug content of 30 w t % of dry polymer showed negative time dependence, indicating that during and after the swelling of the gel, ephedrine started to bind to the polymer . However, the release of ephedrine from a heterogeneous hydrogel increased with time. This shows that the heterogeneous, aggregated polymer binds the hydrophobic substance more strongly than the homogeneous one does, and tha t the homogeneous network has higher affinity for the basic hydrophilic sub stance than the heterogeneous one does. The loading contents of ibuprofen a nd ephedrine affect the release rates in different ways because of the diff erent binding and release mechanisms. The number of binding sites accessibl e for ephedrine inside the polymer network is assumed to change upon the sw elling of the gel. (C) 1999 John Wiley & Sons, Inc.