Influence of silicone elastomer solubility and diffusivity on the in vitro release of drugs from intravaginal rings.
The in vitro release characteristics of eight low-molecular-weight drugs (clindamycin, 17beta-estradiol, 17beta-estradiol-3-acetate, 17beta-estradiol diacetate, metronidazole, norethisterone, norethisterone acetate and oxybutynin) from silicone matrix-type intravaginal rings of various drug loadings have been evaluated under sink conditions. Through modelling of the release data using the Higuchi equation, and determination of the silicone solubility of the drugs, the apparent silicone elastomer diffusion coefficients of the drugs have been calculated. Furthermore, in an attempt to develop a quantitative model for predicting release rates of new drug substances from these vaginal ring devices, it has been observed that linear relationships exist between the log of the silicone solubility of the drug (mg x ml(-1)) and the reciprocal of its melting point (K(-1)) (y=3.558x-9.620, R=0.77), and also between the log of the diffusion coefficient (cm(2) s(-1)) and the molecular weight of the drug molecule (g x mol(-1)) (y=-0.0068x-4.0738, R=0.95). Given that the silicone solubility and silicone diffusion coefficient are the major parameters influencing the permeation of drugs through silicone elastomers, it is now possible to predict through use of the appropriate mathematical equations both matrix-type and reservoir-type intravaginal ring release rates simply from a knowledge of drug melting temperature and molecular weight.
Malcolm
Karl
K
School of Pharmacy, Queen's University of Belfast, 97 Lisburn Road, Belfast, Northern Ireland, BT9 7BL, UK. k.malcolm@qub.ac.uk
Woolfson
David
D
Russell
Julie
J
Tallon
Paul
P
McAuley
Liam
L
Craig
Duncan
D
D000282:Administration, Intravaginal; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003274:Contraceptive Devices, Female / Q000592:standards; D004058:Diffusion / Q000187:drug effects; D012826:Silicone Elastomers / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D012995:Solubility / Q000187:drug effects
D012826:Silicone Elastomers