KINETICS AND THERMODYNAMICS OF DRUG PERMEATION THROUGH SILICONE ELASTOMERS .3. EFFECT OF ALKYL SUBSTITUENT (R) IN (MERSIO)X POLYMER

The effect of silicone polymer structure on the permeability of drug through silicone membranes was investigated in the capsule-type drug delivery system. The permeability, diffusivity and solubility of progesterone and testosterone through polymethylalkylsiloxane membranes, (MeCnH2n+1SiO)x, where n = 1, 2, 3, 6 and 8, were determined at 25, 37 and 50.degree. C respectively. As the size of the alkyl substituent was increased from methyl to octyl, the diffusivity decreased, whereas the solubility increased. As a result, the permeability of progesterone decreased initially but increased gradually thereafter, going from (Me2SiO)x to (MeOctSiO)x, in this series of polymer. The same results were obtained with testosterone; however, permeabilities of testosterone were found to be one order of magnitude lower than those of progesterone. This was attributed to the lower solubilities of testosterone in (MeRSiO)x polymers when compared to those for progesterone. The activation energies of permeation for progesterone in these polymers were found to be in the range of 13-15 Kcal/mol.