Enhanced Release of Drugs from Silicone Elastomers (III): Subcutaneous Controlled Administration of Melatonin for Early Onset of Estrus Cycles in Ewes

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Abstract
Implants were fabricated from swellable silicone elastomers to release hydrophilic melatonin at a controlled rate for the early induction of breeding season in ewes. Both the in vitro and in vivo release profiles of melatonin were observed to follow a linear Q vs. t1/2 [quantity of drug released vs. time] relationship. The in vitro/in vivo release flux ratio ranging from 0.415 to 1.452 was obtained depending upon the polyethylene glycol 400 concentration in the aqueous release medium used for in vitro studies. The release flux (Q/t1/2) of melatonin from the implants was observed to increase as a function of the glycerol content in the silicone elastomers. When the ewes were treated with subdermal implants containing 25% w/w [wt/wt] of melatonin for up to 49 days, blood melatonin levels above the target level of 450-900 pmol/l were achieved and maintained for at least 35 days.