Norgestrel implants

Implanted or depot injection contraception Norgestrel (implant) medroxyprogesterone (intramuscular depot injection)... 

Progestin-only contraceptives (Fig. 4) contain low-doses of progestins (e.g. 350 pg norethindrone or 75 pg norgestrel) that have to be administered daily without interruption. The lowest expected failure rate during the first year of use is 0.5%, while the typical failure rate amounts to 3%. Subdermal implants of norgestrel (216 mg) for sustained release provides for long-term (for up to 5 years) contraceptive effects characterized by failure rates of only 0.05%. Reliable contraception for 3 months can be achieved by an intramuscular injection of a crystalline suspension of 150 mg medroxyprogesterone acetate (Fig. 3) (failure rate 0.3%). 

The earliest reports of controlled release steroids were those of Jackanicz (63), Yolles (64), Anderson (65), and Wise (66). Most of those early studies were based on poly[ (L+)-lactic acid). Implants and granular particles were fabricated with progesterone, norgestrel, and norethisterone. In vivo urinary excretion studies were conducted on [I Cjprogesterone beads (64). The reported results were somewhat questionable as only 20% of the original implanted drug could be accounted for. 

Only one implantable contraceptive preparation is available at present. Norgestrel, also utilized as the progestin component of some oral contraceptive preparations, is an effective suppressant of ovulation when it is released from subcutaneous implants. Intramuscular injection of large doses of medroxyprogesterone also provides contraceptive action of long duration. 

Figure 7. Daily rate of release of norgestrel from polyfw-caprolactone) capsule implanted in rat after 32 days in vitro. (Reprinted with permission from Ref. 4. Copyright 1980, Academic Press,...

Depot contraception (medroxyprogesterone IM every 3 months), and implant (norgestrel 5 years). 

Norgestrel Progestin used in many oral contraceptives and Norplant implantable contra-... 

The clinical use of low-dose progestagens produced few reported severe side-effects. Women with subcutaneously implanted silastic capsules containing MA have had few side-effects and no gross evidence of total tissue reaction from the silastic.Norgestrel, at a dally dose of 50 pg, did not decrease glucose tolerance or raise serum transaminase levels. 6... 

The in-vivo controlled release of norgestrel from PCL capsules implanted in rats was reported by Pitt and Schindler (1980a). This study showed that a constant release rate of 8-10 micrograms/day/cm capsule could be attained over a period of292 days. This paper gives a valuable comprehensive review of the related literature concerning numerous other polymeric drug delivery systems. 

In a related paper, Pitt, Marks, and Schindler (1980) reported similar results with naltrexone delivery pertinent to narcotic antagonist therapy. This study used radiolabelled naltrexone delivered to monkeys via implanted capsules made from a copolymer of caprolactone and D,L-lactide. Acute stage efficacy was obseiv ed over the course of 33 days with this system, even though the delivery rate was not quite zero order as with the norgestrel study. 

---