| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1992: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1991: ¥800,000 (Direct Cost: ¥800,000)
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| Research Abstract |
To obtain relationships between chemical structures of polymers and transport properties of pharmaceuticals and veterinary drugs such as steroids is important to design membrane permeation-controlled drug delivery systems. Three kinds of steroids, totally nine steroids namely androstenedione series, 11-deoxycorticosterone series and 11-deoxy-17-hydroxycorticosterone series which differ chemical structure of a side group at 11-position of a sterine cyclic hydrocarbon bone.
As polymeric membranes, copolymer membranes of styrene sulfonic acid (SSA) and methyl methacrylate (MMA), copoly(SSA-MMA) membranes whose contents of SSA are different were synthesized as an usual way, and a polydimethylsiloxane (PDMS) membrane, Silastic(] SY.encircledR.[) were used. The total water content and the content of freezing-water and non-freezing water were decided at 37ﾟC. Permeability coefficient(P), partition coefficient (K) were measured experimentally at 37ﾟC and diffusion coefficient (D) was calculated
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by P/K. The permeability coefficients of steroids were measured by dialysis technique using the ultraviolet spectrometry.
The effect of hydration of copoly(SSA-MMA) membranes on the transport properties of steroids is as follows : 1) the permeability coefficient increased remarkably with increasing of the total water content a nd not of the content of the freezing-water, 2) no effect was observed of the different kinds of steroids. However, the high partition coefficient was obtained in copoly(SSA-MMA) membranes with a lower hydration. Therefore, if a polymeric hydrohobic membrane with large inter-segmental distances, namely with high diffusivity, the membrane is expected to give us high permeability of steroids. Such a membrane should be PDMS membrane. The permeability coefficient of PDMS membrane to nine steroids differed and decreased with increasing of hydrophilicity in each series of steroids. The expectation of the high parti-ion coefficient in the PDMS membrane was on contrary, however, androstenedione which is the highest hydrohobic steroid in this program showed the same order of high permeability of the copoly(SSA-MMA) membrane with the highest water content. The effect of hydrohobicity of the membrane on the diffusivity of steroids was discussed. Less
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