Methoxy-polyethoxy side-chain silastomers as materials controlling drug delivery by diffusion flux.
The density of a diffusion medium and the solubility of the diffusant in this material are predominant parameters which control the diffusion flux. Side-chain silastomers can be structurally modified in such a manner that density and polarity are widely varied and adjustable to distinct conditions. The synthesis of cross-linked methoxy-polyethoxy side-chain polysiloxanes is performed by reaction of alpha, omega-bis-(trimethyl-silyloxy)-poly-(methyl-hydrogen-siloxane), alpha, omega-divinyl-poly-(dimethyl-siloxane), and 4-propenyloxy-(4'-methoxy-polyethoxy)-biphenyl. Silastomer foils were obtained with side-chains having up to 9 ethoxy groups. Various silastomer types were characterized by DSC-measurements, polarization microscopy, uptake of water and salicylic acid (as model drug), and by permeation measurements. The polarity of the polymers depends on their contents of ethoxy groups influencing the uptake of polar substances. Polymers with penta-ethoxy and hepta-ethoxy groups at the side-chains take up water under swelling. The solubility and the distribution coefficients of salicylic acid are linearly correlated to the weight fractions of the methoxy-polyethoxy groups in all silastomer types. The temperature dependence of the distribution coefficients of the penta-ethoxy and hepta-ethoxy polymer types shows deviations from the Arrhenius equation. As the side-chains occupy considerable volumes, the density of the molecular packing within the cross-linked polysiloxane matrices is high. The arrangement of the side-chain domains, therefore, depends on the chain length of the cross-linker; the diffusion coefficients are influenced by this parameter. Evidence for the existence of a lyotropic liquid-crystalline phase was observed for one type of these polymers only. Methoxy-polyethoxy side-chain silastomers as membranes or matrices are suited for controlled drug delivery. Drug liberation rates and swelling by uptake of water can be widely altered by variations of the side-chain structures.
Fachrichtung Biopharmazie und Pharmazeutische Technologie der Universität des Saarlandes, Saarbrücken, Germany.
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D004058:Diffusion; D016503:Drug Delivery Systems; D008970:Molecular Weight; D010539:Permeability; D010592:Pharmaceutic Aids; D011092:Polyethylene Glycols; D012826:Silicone Elastomers; D012995:Solubility; D013816:Thermodynamics
D010592:Pharmaceutic Aids; D012826:Silicone Elastomers; D011092:Polyethylene Glycols