High-performance liquid chromatographic determination of 17beta-estradiol and 17beta-estradiol-3-acetate solubilities and diffusion coefficents in silicone elastromeric intravaginal rings.
A rapid, sensitive reversed-phase high-performance liquid chromatographic method has been developed for the determination of in vitro release of 17beta-estradiol and its ester prodrug, 17beta-estradiol-3-acetate, from silicone intravaginal rings. Partial hydrolysis of the acetate under the aqueous conditions provided by the 1% benzalkonium chloride release medium necessitates its conversion to 17beta-estradiol prior to HPLC analysis. Both steroid peaks have been fully resolved from the benzalkonium chloride peaks by the reported chromatographic method, which employs a C18 bonded reversed-phase column, an acetonitrile-water (50:50, v/v) mobile phase and a UV detection wavelength of 281 nm. The peak area versus 17beta-estradiol concentration was found to be linear over the range of 0.0137-1347 microkg ml(-1). The HPLC method has also been used to determine the silicone solubilities and diffusion coefficients of the two related steroids. The almost 100-fold increase in 17beta-estradiol-3-acetate release from the silicone core-type intravaginal rings compared to 17beta-estradiol is shown to be due to a 60-fold increase in silicone solubility and a one and a half-fold increase in diffusitivity. The results demonstrate that an effective estrogen replacement therapy dose of 17beta-estradiol may be administered from a silicone intravaginal reservoir device containing the labile 17beta-estradiol-3-acetate prodrug.
Russell
J A
JA
School of Pharmacy, The Queen's University of Belfast, UK.
Malcolm
R K
RK
Campbell
K
K
Woolfson
A D
AD
D000282:Administration, Intravaginal; D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004058:Diffusion; D020724:Elastomers / Q000737:chemistry; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000032:analysis*; D020249:Hormone Replacement Therapy; D006868:Hydrolysis; D012828:Silicones / Q000737:chemistry; D012995:Solubility
D020724:Elastomers; D012828:Silicones; D004958:Estradiol; C072350:estradiol 17-acetate