Advances in drug delivery: modern drug delivery systems for contraception.

Controlled drug delivery systems are vehicles which regulate the release of a drug to the target tissues. They are ideally suitable for contraceptives because they eliminate daily administration and reduce the steroid load which may cause delayed return of fertility on termination or cancer. 5 kinds of contraceptive drug delivery systems are in use: monthly injections very long-acting injections medicated IUDs or vaginal rings nondegradable implants and biodegradable implants. Monthly injections may consist of an estrogen-progesterone combination a progestagen alone or an estrogen alone. The progestagens used a medroxyprogesterone acetate (depo-progesterone) algestone acetofenid (dihydroxyprogesterone acetophenide) hydroxyprogesterone caproate norgestrel and norethisterone enanthate. The estrogen component is usually estradiol (cipionate enanthate valerate undecylate hexahydrobenzoate or benzoate butyrate ester). Steroid release is prolonged by esterification or by using a crystal suspension. Two injectables are on or near the market: Deladroxate and Cyclo-Provera. Long-acting injectable contraceptives are progesterone derivatives whose action is prolonged by solubility limitations or by formation of prodrugs. 2 commercial products are available: Depo-Provera (medroxyprogesterone acetate) and Norigest (norethisterone enanthate) Medroxyprogesterone acetate suppresses ovulation at the hypothalamic level; norethisterone enanthate acts on the hypothalamus and later on the cervix and uterus. Medicated IUDs usually use copper progesterone and levonorgestrel as active agents. The disadvantage of IUDs is that they must be inserted by medical personnel. The 2 most common medicated IUDs are the Progestasert which prevents blastocyst implantation by releasing 65ug a day of progesterone; and the Cu-7 which releases 9.87 ug copper a day. Vaginal rings made of polysiloxane (Silastic 82) release steroid (medroxyprogesterone acetate norethisterone norgestrel or levonorgestrel) that inhibits ovulation and prevents sperm penetration. The rings may be removed for intercourse. Nondegradable implants are silastic capsules or rods implanted subdermally which may be retained for 2 to 7 years. Their disadvantages are that they must be medically implanted and they may migrate. Their mode of action is interference with ovulation or luteal function. The most extensively used is Norplant. Biodegradable polymers include polyepsilon caprolactone polyglycolic acid and polylactic acid containing microspheres of norethisterone. The steroid is released over 6 months and the polymer biodegrades within 6 to 12 months.