Steroid release from poly

Controlled release fiber systems based on aliphatic polyesters were investigated by Dunn and Lewis (51-54). The feasibility of hollow fibers spun from poly (L-lactide) and containing the contraceptive steroid levonorgestrel has been demonstrated (55). 

J. Heller, D.W.H. Penhale, R. F. Helwing, and B. K. Fritzinger, Controlled Release of Steroids from Poly(0rtho Esters), in "Controlled Release Delivery Systems, T J. Rosemand and... 

In another study, Pitt and others compared the steroidal release kinetics of caprolactone homopolymer, D,L-lactide homopolymer, and their related copolymers to silicone rubber. While the observed release rates from the poly (D,L-lactide) were much slower than any of the other materials studied,incorporation of a plasticizer such as tributy l citrate into the poly(D,Lrlactide) seemed to increase the release rates. The other caprolactone-based materials showed release kinetics similar to that of silicone rubber (Pitt et al, 1979b). 

Only a limited number of release studies were undertaken with monolithic devices. In vitro release of progesterone from poly(caprolactone) films is shown in Fig. 12 for different loads of steroid (10-30% w/w). Apart from an initial induction period, the amounts released are proportional to the square root of time until about 80% of the steroid are released. In contrast, less than 1% of progesterone was released from films of poly(DL-lactide) in a comparable time period (36 hrs.)... 

Fig. 13 - In vitro release of progesterone from poly-(glycolide-co-dilactide) films containing 10% (w/w) steroid. For copolymer identification see text.

Heller, J., Penhale, D. W. H., Fritzinger, B. K., Rose, J. E., and Helwing, R. F., Controlled release of contraceptive steroids from biodegradable poly(ortho esters), Contracept. Deliv. Syst., 4, 43-53, 1983. 

J. E., Synthesis and release of contraceptive steroids from bio-erodible poly(ortho esters), in Polymers in Medicine (E. Chielini and P. Giusti, eds.). Plenum Publishing, New York, 1983, pp. 169-178. 

Polymer-other species have also been described in the literature. Carriers of vitamin E have been prepared from a-tocopherol methacrylate monomers. These would have potential use as antioxidants to protect against cellular damage. Poly(acrylate)s that release non-steroidal anti-inflammatory drugs (NSAIDs) through hydrolysis of links to the backbone have also been described. ... 

Release of levonorgestrei. Considerable work has been expended on the development of a poly (ortho ester) implant that can deliver a contraceptive steroid from a subcutaneous or intramuscular implant for about one year at close to zero order kinetics and where drug depletion and polymer erosion occur at about the same time. Initial funding for the development for the poly (ortho ester) II system was provided by the Contraceptive Development Branch of NIH with the objective of developing such a contraceptive system. 

SYNTHESIS AND RELEASE OF CONTRACEPTIVE STEROIDS FROM BIOERODIBLE POLY(ORTHO ESTER) S... 

In a related study, Pitt and others (1979a) reported release rates of various steroids from monolithic films and capsules made from homopolymeric PCL, poly (D,L-lactide), and copolymers of caprolactone and D,L-lactide (in both 60/40 and 90/10 caprolactone/D,Lrlactide acid ratios), and copolymers of glycolic acid with D,L-lactide. The release rates of the steroids from the caprolactone-co-lactide polymers were similar to the homopolymeric PCL. However, the release rates from the glycolide-co-lactide polymers were much slower than those observed with PCL. Further data analysis revealed that the obseiv ed release kinetics depended upon the steroid dissolution rate (in the polymer) and the polymer cry stallinity. WTiile it is outside the scope of the current discussion, a good background reference on PCL thermodynamics and crystallinity is given by Lebedev (1979) and Chynoweth Stachurscki (1986). 

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