Dual-controlled drug delivery across biodegradable copolymer. I. Delivery kinetics of levonorgestrel and estradiol through (caprolactone/lactide) block copolymer.
Four block copolymers of caprolactone (CL) and dl-lactide (LA) with varying weight fractions were synthesized by living polymerization in the presence of Al/Zn bimetallic alkoxide complex. The solubility of levonorgestrel (LNG) and estradiol (E2) in the copolymers was evaluated and found to increase exponentially with CL mole fraction. Their aqueous solubilities were also studied and observed to increase linearly with the concentration of benzalkonium chloride (BAC), a solubilizer. The kinetics of LNG and E2 permeation through the copolymer membranes were studied and observed to follow a zero-order kinetics, and the permeation rates obtained were noted to be a function of copolymer composition. The release kinetics through the copolymer matrix were also studied and noted to follow a matrix-diffusion process, and the release flux was found to be dependent on copolymer composition. Permeation rates and release fluxes at steady state as well as the permeability and solubility of LNG and E2 in the copolymers suggest that these permeation parameters are affected by copolymer composition, which increase as the CL/LA ratio in the copolymer was increased.
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Controlled Drug-Delivery Research Center, College of Pharmacy, Rutgers University, Piscataway, New Jersey 08854, USA.
Chien
Y W
YW
D001711:Biotransformation; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002851:Chromatography, High Pressure Liquid; D003271:Contraceptive Agents, Female / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004058:Diffusion; D004958:Estradiol / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016912:Levonorgestrel / Q000008:administration & dosage* / Q000493:pharmacokinetics; D010539:Permeability; D011091:Polyesters / Q000737:chemistry; D012995:Solubility
D003271:Contraceptive Agents, Female; D011091:Polyesters; D004958:Estradiol; D016912:Levonorgestrel; C062968:lactide-caprolactone copolymer