Kinetics and Thermodynamics of Drug Permeation Through Silicone Elastomers (I) Effect of Penetrant Hydrophilicity

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Abstract
The hydrophilicity of progesterone, a lipophilic penetrant, was progres sively increased by addition of one or more hydroxy substituents at different positions on the steroid skeleton. Effects of these hydrophilic substituents on the kinetics and thermodynamics of permeation of progesterone molecules through polydimethylsiloxane and polytrifluoropropylmethylsiloxane membranes were studied. The addition of OH groups was found to reduce substantially the apparent and intrinsic permeation rates of progesterone. The magnitude of this reduction was observed to be dependent upon the number and the position of hydroxy groups and could be attributed to the decrease in the polymer solubility and the increase in the aqueous solubility of progesterone molecules. A remarkable difference was observed between the intrinsic and apparent rates of permeation for progesterone, while no significant difference for the hydroxyl derivatives of progesterone. The rate of permeation increased with temperature as expected from the Arrhenius relationship. The energy required for membrane permeation was noted to be relatively constant and independent of hydroxylation. After normalization, the membrane permeability of progesterone derivatives was found to be higher in polydi methylsiloxane than in polytrifluoropropylmethylsiloxane, which can be attributed to the substitution of methyl group in the polydimethylsiloxane backbone by a more polar and bulkier trifluoropropyl substituent. The substituent effect of trifluoropropyl group is substantial for progesterone but less significant for hydroxy derivatives.