Transdermal estrogen/progestin dosage unit, system and process

A fertility-control system comprising one or more series of three transdermal absorption dosage units, said dosage units being transdermal estrogen/progestin dosage units comprising:

• a) a backing layer which is substantially impervious to the estrogen and progestin hormones to be delivered transdermally;
• b) a polymer layer which is adhered to said backing layer and which has dissolved and/or microdispersed therein an effective dosage amount of one or more effective estrogens absorbable transdermally and re pharmaceutically acceptable, said polymer being bioacceptable, providing a compatible environment for said one or more estrogens and permitting said one or more estrogens to be transmitted for transdermal absorption, and
• c) an adhesive layer in intimate contact with said polymer layer, said adhesive layer having dissolved and/or microdispersed therein an effective dosage amount of one or more effective progestins selected from the group consisting of norgestrel, levonorgestrel, and biocompatible derivatives or norgestrel and levonorgestrel, which are absorbable transdermally and are pharmaceutically acceptable, said adhesive layer being bioacceptable, providing a compatible environment for said one or more progestins, and permitting said one or more progestins and said one or more estrogens to be transmitted for transdermal absorption, said adhesive layer having an effective amount of transdermal skin absorption enhancing agent;
• said hormones being stable in said polymer and adhesive layers and being transdermally absorbed simultaneously to provide at least minimum effective daily doses of said hormones to effect fertility control, each dosage unit of which provides at least minimum effective daily dosage amounts of estrogen and progestin for about one week, said dosage units to be applied serially for about one week each, the first dosage unit to be applied about on the fifth day of the menstrual cycle, the second and third dosage units to be applied about 7 and about 14 days later, respectively, said application of said series of three transdermal absorption units to be repeated as desired to control fertility.

A fertility control system comprising one or more series of three transdermal dosage units, each dosage unit providing at least minimum effective daily dosage amounts of estrogen and progestin for about one week, said dosage units to be applied serially for about one week each, the first dosage unit to be applied about on the fifth day of the menstrual cycle, the second and third dosage units to be applied about 7 and 14 days thereafter, respectively;

• said dosage units comprising:
• a) a backing layer which is substantially impervious to the estrogen and progestin hormones to be delivered transdermally;
• b) a polymer layer which is adhered to said backing layer and which has dissolved and/or microdispersed therein an effective dosage amount of one or more effective estrogens absorbable transdermally and are pharmaceutically acceptable, said polymer being bioacceptable, providing a compatible environment for said one or more estrogens and permitting said one or more estrogens to be transmitted for transdermal absorption.
• c) adhesive layer having dissolved and/or microdispersed therein an effective dosage amount of one or more effective progestins, which are absorbable transdermally and are pharmaceutically acceptable, said adhesive layer being bioacceptable, providing a compatible environment for said one or more progestins, and permitting said one or more progestins and said one or more estrogens to be transmitted for transdermal absorption, said adhesive layer having an effective amount of transdermal skin absorption enhancing agent;
• and
• d) a separating layer made of a bioacceptable adhesive or polymer located between said polymer and adhesive layers and in intimate contact therewith through which said one or more estrogens are transmitted for desired transdermal absorption, said separating layer made using an adhesive or polymer which is free or substantially free of estrogen, progestin and enhancing agents;
• said hormones being stable in said polymer and adhesive layers and being transdermally absorbed simultaneously to provide at least minimum effective daily doses of said hormones to effect fertility control or estrogen replacement therapy;
• said dosage units further characterized as follows:
• a) first dosage unit having a progestin/estrogen transdermal absorption rate ratio from about 0.75/1 to about 1.25/1 based upon the progestin being levonorgestrel or levonorgestrel bioequivalent amount transdermally absorbed of another progestin used as said progestin and further based upon the estrogen being 17-beta-estradiol or 17-beta-estradiol bioequivalent amount transdermally absorbed of another estrogen used as said estrogen;
• b) second dosage unit having a progestin/estrogen transdermal absorption rate ratio from about 1.25/1 to about 2.5/1 based upon the progestin being levonorgestrel or levonorgestrel bioequivalent amount transdermally absorbed of another progestin used as said progestin and further based upon the estrogen being 17-beta-estradiol or a 17-beat-estradiol bioequivalent amount transdermally absorbed of another estrogen used as said progestin;
• and
• c) third dosage unit having a progestin/estrogen transdermal absorption rate ratio from about 2/1 to about 5/1 based upon the progestin being levonorgestrel or levonorgestrel bioequivalent amount transdermally absorbed of another progestin used as said progestin and further based upon the estrogen being 17-beta-estradiol or a 17-beta-estradiol bioequivalent amount transdermally absorbed of another estrogen used as said estrogen.

A process of estrogen replacement therapy by applying successively to the skin of a subject needing said therapy, dosage units which are transdermal estrogen-orgestin dosage units comprising:

• a) a backing layer which is substantially impervious to the estrogen and progestin hormones to be delivered transdermally;
• b) a polymer layer which is adhered to said backing layer and which has dissolved and/or microdispersed therein an effective dosage amount of one or more effective estrogens absorbable transdermally and are pharmaceutically acceptable, said polymer being bioacceptable, providing a compatible environment for said one or more estrogens and permitting said one or more estrogens to be transmitted for transdermal absorption, and
• c) an adhesive layer in intimate contact with said polymer layer, said adhesive layer having dissolved and/or microdispersed therein an effective dosage amount of one or more effective progestins selected from the group consisting of norgestrel, levonorgestrel, and biocompatible derivatives or norgestrel and levonorgestrel, which are absorbable transdermally and are pharmaceutically acceptable, said adhesive layer being bioacceptable, providing a compatible environment for said one or more progestins, and permitting said one or more progestins and said one or more estrogens to be transmitted for transdermal absorption, said adhesive layer having an effective amount of transdermal skin absorption enhancing agent;
• said hormones being stable in said polymer and adhesive layers and being transdermally absorbed simultaneously to provide at least minimum effective daily doses of said hormones to effect estrogen replacement therapy, which provide effective dosages respectively of one or more estrogens and one or more progestins for said replacement therapy.