Pharmaceutical composition for use as a contraceptive

Abstract

A pharmaceutical composition comprises, as a first active agent, 6β,7β;15β,16β-dimethylene-3-oxo-17α-pregn-4-ene-21,17-carbolactone (drospirenone) in an amount corresponding to a daily dosage, on administration of the composition, of from about 2 mg to about 4 mg, and, as a second active agent, 17α-ethinylestradiol (ethinylestradiol) in an amount corresponding to a daily dosage of from about 0.01 mg to about 0.05 mg, together with one or more pharmaceutically acceptable carriers or excipients. In a specific embodiment, the composition consists of a number of separately packaged and-individually removable daily dosage units placed in a packaging unit and intended for oral administration for a period of at least 21 consecutive days, wherein said daily dosage units comprises the combination of drospirenone and ethinylestradiol. The composition may further comprise 7 or less daily dosage units containing no active agent or containing ethinylestradiol alone.

1 . A pharmaceutical composition comprising, as a first active agent, 6β,7β;15β,16β-dimethylene-3-oxo-17α-pregn-4-ene-21,17-carbolactone (drospirenone) in an amount corresponding to a daily dosage, on administration of the composition, of from about 2 mg to about 4 mg, and, as a second active agent, 17α-ethinylestradiol (ethinylestradiol) in an amount corresponding to a daily dosage of from about 0.01 mg to about 0.05 mg, together with one or more pharmaceutically acceptable carriers or excipients.  
     
     
         2 . A composition according to  claim 1  wherein the drospirenone is in micronized form or sprayed from a solution onto particles of an inert carrier.  
     
     
         3 . A composition according to  claim 1  or  2 , comprising drospirenone in an amount corresponding to a daily dosage of from about 2.5 mg to about 3.5 mg, in particular about 3 mg.  
     
     
         4 . A composition according to  claim 1  wherein the ethinylestradiol is in micronized form or sprayed from a solution onto particles of an inert carrier.  
     
     
         5 . A composition according to  claim 1 , comprising ethinylestradiol in an amount corresponding to a daily dosage of from about 0.015 mg to about 0.04 mg, in particular from about 0.02 mg to about 0.03 mg.  
     
     
         6 . A composition according to  claim 1 , comprising an amount of drospirenone corresponding to a daily dosage of from about 3.0 to about 3.5 mg and ethinylestradiol in an amount corresponding to from about 0.015 to about 0.03 mg, in particular comprising an amount of drospirenone corresponding to a daily dosage of about 3.0 mg and ethinylestradiol in an amount corresponding to a daily dosage of 0.03 mg.  
     
     
         7 . A composition according to  claim 1  wherein the pharmaceutically acceptable carrier or excipient is selected so as to promote rapid dissolution of the first and second active agents.  
     
     
         8 . A composition according to  claim 1  wherein at least 70% of the first and second active substance are released within 30 minutes of administration thereof.  
     
     
         9 . A composition according to  claim 8 , wherein at least 80% of the first and second active agents are released within 20 minutes of administration thereof.  
     
     
         10 . A pharmaceutical preparation consisting of a number of separately packaged and individually removable daily dosage units placed in a packaging unit and intended for oral administration for a period of at least 21 consecutive days, wherein said daily dosage units comprises a combination of drospirenone in an amount of from about 2 mg to about 4 mg and ethinylestradiol in an amount from about 0.01 to about 0.05 mg.  
     
     
         11 . A preparation according to  claim 10 , which additionally comprises 7 or less daily dosage units containing no active agent intended for oral administration subsequent to the period of at least 21 consecutive days, the total number of daily dosage units being at least 28.  
     
     
         12 . A preparation according to  claim 10  or  11 , wherein the number of daily dosage units comprising the combination of drospirenone and ethinylestradiol is 21, 22, 23 or 24, and wherein the number of daily dosage units containing no active agent is 7, 6, 5 or 4.  
     
     
         13 . A preparation according to  claim 10 , wherein the number of daily dosage units comprising the combination of drospirenone and ethinylestradiol is 28, or a multiple of 28 such as 2-4, in particular 2 or 3, times 28.  
     
     
         14 . A preparation according to  claim 13 , which additionally comprises a number of daily dosage units comprising the combination of drospirenone and ethinylestradiol of 21, 22, 23 or 24, and a number of daily dosage units containing no active agent of 7, 6, 5 or 4.  
     
     
         15 . A preparation according to  claim 10 , wherein the at least 21 daily dosage units comprise drospirenone and ethinylestradiol in micronized form or sprayed from a solution onto particles of an inert carrier.  
     
     
         16 . A preparation according to  claim 10  wherein the at least 21 daily dosage units comprise drospirenone in an amount of from about 2.5 mg to about 3.5 mg, in particular about 3 mg, and ethinylestradiol in an amount of from about 0.015 mg to about 0.04 mg, in particular from about 0.015 mg to about 0.03 mg.  
     
     
         17 . A preparation according to  claim 10 , wherein the at least 21 daily dosage units comprise drospirenone in an amount of from about 3.0 to about 3.5 mg and ethinylestradiol in an amount corresponding to from about 0.015 to about 0.03 mg.  
     
     
         18 . A pharmaceutical preparation consisting of a number of separately packaged and individually removable daily dosage units placed in a packaging unit and intended for oral administration for a period of at least 28 consecutive days, wherein at least 21 of said daily dosage units comprises a combination of drospirenone in an amount of from about 2 mg to about 4 mg and ethinylestradiol in an amount from about 0.01 to about 0.05 mg, and wherein 7 or less of said daily dosage units contain ethinylestradiol alone in an amount from about 0.01 to about 0.05 mg.  
     
     
         19 . A preparation according to  claim 18 , wherein the number of daily dosage units comprising the combination of drospirenone and ethinylestradiol is 21, 22, 23 or 24, and wherein the number of daily dosage units comprising ethinylestradiol alone is 7, 6, 5 or 4.  
     
     
         20 . A preparation according to  claim 18  or  19 , wherein the at least 21 daily dosage units comprise drospirenone and ethinylestradiol in micronized form or sprayed from a solution onto particles of an inert carrier.  
     
     
         21 . A preparation according to  claim 18 , wherein the at least 21 daily dosage units comprise drospirenone in an amount of from about 2.5 mg to about 3.5 mg, in particular about 3 mg, and ethinylestradiol in an amount of from about 0.015 mg to about 0.04 mg, in particular from about 0.02 mg to about 0.03 mg.  
     
     
         22 . A preparation according to  claim 18 , wherein the at least 21 daily dosage units comprise drospirenone in an amount of from about 3.0 to about 3.5 mg and ethinylestradiol in an amount corresponding to from about 0.015 to about 0.03 mg.  
     
     
         23 . A method of inhibiting ovulation in a mammal, in particular a human, comprising administering, to said mammal, drospirenone in an amount in the range of from about 2 mg to about 4 mg of per day, together with ethinylestradiol in an amount of from about 0.01 mg to about 0.05 mg per day, said amounts being effective to inhibit ovulation in said mammal.  
     
     
         24 . A method according to  claim 23 , wherein the amount of drospirenone is in the range of from about 2.5 mg to about 3.5 mg, in particular about 3 mg of drospirenone per day.  
     
     
         25 . A method according to  claim 23 , wherein the amount of ethinylestradiol is from about 0.015 mg to about 0.04 mg, in particular from about 0.015 to about 0.03 mg per day.  
     
     
         26 . A method of preventing or treating androgen-induced disorders in a female mammal, in particular a female human, comprising administering, to said mammal, an amount of drospirenone in the range of from about 2 mg to about 4 mg per day, together with an amount of ethinylestradiol of from about 0.01 mg to about 0.05 mg per day, said amounts being effective to prevent or treat androgen-induced disorders in said mammal.  
     
     
         27 . A method according to  claim 26 , wherein the androgen-induced disorder is acne.  
     
     
         28 . A method of inhibiting ovulation in a mammal, in particular a human, comprising administering, to said mammal, on each day of at least 21 consecutive days, a daily dosage unit comprising a combination of drospirenone in an amount of from about 2 mg to about 4 mg and ethinylestradiol in an amount from about 0.01 to about 0.05 mg, followed by administering, on each day of 7 or less consecutive days, a daily dosage unit containing no active agent, or alternatively administering no daily dosage units for 7 or less consecutive days.  
     
     
         29 . A method according to  claim 28 , wherein the daily dosage units comprising the combination of drospirenone and ethinylestradiol are administered for 21, 22, 23 or 24 consecutive days, and wherein no daily dosage units or daily dosage units containing no active agent are administered for 7, 6, 5 or 4 consecutive days.  
     
     
         30 . A method according to  claim 28 , wherein the daily dosage units comprising the combination of drospirenone and ethinylestradiol are administered for 28 consecutive days.  
     
     
         31 . A method according to  claim 28 , wherein the daily dosage units comprising the combination of drospirenone and ethinylestradiol are administered for 2-4, preferably 2 or 3, times 28 consecutive days, followed by administration of the daily dosage units comprising the combination of drospirenone and ethinylestradiol for 21 consecutive days and subsequently administration of the daily dosage units containing no active agent, or alternatively no daily dosage units, for 7 consecutive days.  
     
     
         32 . A method of inhibiting ovulation in a mammal, in particular a human, comprising administering, to said mammal, on each day of at least 21 consecutive days, a daily dosage unit comprising a combination of drospirenone in an amount of from about 2 mg to about 4 mg and ethinylestradiol in an amount from about 0.01 to about 0.05 mg, followed by administering, on each day of 7 or less consecutive days, a daily dosage unit containing ethinylestradiol alone in an amount of from about 0.01 mg to about 0.05 mg.  
     
     
         33 . A method according to  claim 32 , wherein the daily dosage units comprising the combination of drospirenone and ethinylestradiol are administered for 21, 22, 23 or 24 consecutive days, and wherein the daily dosage units comprising ethinylestradiol alone are administered for 7, 6, 5 or 4 consecutive days.  
     
     
         34 . A method according to  claim 32 , wherein the daily dosage units comprising the combination of drospirenone and ethinylestradiol are administered for 2-4, preferably 2 or 3, times 28 consecutive days, followed by administration of the daily dosage units comprising the combination of drospirenone and ethinylestradiol for 21 consecutive days and subsequently administration of the daily dosage units comprising ethinylestradiol alone for 7 consecutive days.  
     
     
         35 . A method of promoting rapid dissolution of drospirenone from a unit dosage form on oral administration, the method comprising providing drospirenone in micronized form in said unit dosage form, or sprayed from a solution onto particles of an inert carrier in admixture with one or more pharmaceutically acceptable excipients that promote dissolution of the drospirenone.