Influence of betacyclodextrin on the release of poorly soluble drugs from inert and hydrophilic heterogeneous polymeric matrices

The release behavior of poorly soluble drugs (naproxen and ketoprofen) from inert (acrylic resins) and hydrophilic swellable (high-viscosity hydroxypr opylmethylcellulose) tableted matrices containing betacyclodextrin (betaCD) was investigated. The results demonstrated that, in both cases, betaCD can enhance the rate of drug release. Matrices obtained from formulations in w hich lactose replaced betaCD were also evaluated. BetaCD in inert matrices causes a dramatic increase in the rate of drug release, higher than that pr omoted by lactose which merely acts as a channelling agent. This result sug gests that possible in situ formation of the drug-betaCD complex, which Cau ses an improvement in apparent drug solubility, could have a greater influe nce on the rate of drug release than the possible increase of water uptake by a soluble filler. Indeed, if the opposite were true, lactose would be mo re effective in increasing the rate of drug release than betaCD, because of its greater solubility in water. On the contrary, in the case of hydrophil ic matrices. lactose proves to be much more effective in promoting drug rel ease than betaCD. It seems that, while the bulky interaction compound can f reely diffuse through water-filled pores of inert systems, its diffusion th rough swollen macromolecular chains of hydrophilic matrices may be hindered . This hypothesis was supported by data obtained from binary (drug/polymer) and ternary (drug/polymer/betaCD) hydrophilic matrices using a betaCD-cont aining dissolution media. (C) 2001 Elsevier Science Ltd. All rights reserve d.