Pharmaceutical composition for use as a contraceptive

Abstract

A pharmaceutical composition comprises, as a first active agent, 6β,7β;15β,16β-dimethene-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 .- 35 . (canceled) 
     
     
         36 . A pharmaceutical composition comprising ethinylestradiol and inert carrier particles containing drospirenone on their surface, wherein
 drospirenone is present in the composition in an amount corresponding to a daily dosage of from about 2 mg to about 4 mg;   ethinylestradiol is present in the composition in an amount corresponding to a daily dosage of from about 0.01 mg to about 0.05 mg; and   at least 70% of said drospirenone is dissolved from said composition within 30 minutes, as determined by USP XXIII Paddle Method II using water at 37° C. as the dissolution media and 50 rpm as the stirring rate.   
     
     
         37 . The composition according to  claim 36 , wherein said composition comprises inert carrier particles containing ethinylestradiol on their surface. 
     
     
         38 . The composition according to  claim 36  or  37 , wherein said composition further comprises a carrier or excipient which acts to promote dissolution of both active substances. 
     
     
         39 . The composition according to  claim 38 , wherein said carrier or excipient is selected from the group consisting of carboxymethyl cellulose, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, gelled starch, gelatin and polyvinylpyrrolidone. 
     
     
         40 . The composition according to  claim 39 , wherein said carrier or excipient is polyvinylpyrrolidone. 
     
     
         41 . The composition according to  claim 36 ,  37 ,  39  or  40 , wherein at least 80% of said drospirenone is dissolved from said composition within 20 minutes, as determined by USP XXIII Paddle Method II using water at 37° C. as the dissolution media and 50 rpm as the stirring rate. 
     
     
         42 . The composition according to  claim 36 ,  37 ,  39  or  40 , wherein drospirenone is present in an amount corresponding to a daily dosage of from 2.5 mg to 3.5 mg. 
     
     
         43 . The composition according to  claim 42 , wherein drospirenone is present in an amount corresponding to a daily dosage of about 3 mg. 
     
     
         44 . The composition according to  claims 36 ,  37 ,  39  and  40 , wherein ethinylestradiol is present in an amount corresponding to a daily dosage of from 0.015 mg to 0.03 mg. 
     
     
         45 . The composition according to  claim 36 ,  37 ,  39  or  40 , wherein said composition is in the form of an oral dosage unit. 
     
     
         46 . The composition according to  claim 45 , wherein said oral dosage unit is in the form of a tablet, a capsule or a pill. 
     
     
         47 . The composition according to  claim 41 , wherein drospirenone is present in an amount corresponding to a daily dosage of about 3 mg. 
     
     
         48 . The composition according to  claim 43 , wherein ethinylestradiol is present in an amount corresponding to a daily dosage of from 0.015 mg to 0.03 mg. 
     
     
         49 . The composition according to  claim 48 , wherein said composition is in the form of an oral dosage unit. 
     
     
         50 . A pharmaceutical preparation comprising a number of separately packaged and individually removable oral dosage units as defined in  claim 45  placed in a packaging unit and intended for oral administration for a period of at least 21 consecutive days. 
     
     
         51 . The preparation according to  claim 50 , wherein the number of oral dosage units is 28, or a multiple of 28. 
     
     
         52 . The preparation according to  claim 51 , wherein the number of oral dosage units is 2 times 28, 3 times 38, or 4 times 28. 
     
     
         53 . The preparation according to  claim 50 , which additionally comprises 7 or less oral dosage units containing no active agent intended for oral administration subsequent to the period of at least 21 days, the total number of daily dosage units being at least 28. 
     
     
         54 . The preparation according to  claim 52 , wherein the number of oral dosage units is 21, 22, 23, or 24, and wherein the number of oral dosage units containing no active agent is 7, 6, 5 or 4. 
     
     
         55 . A pharmaceutical preparation comprising a number of separately packaged and individually removable oral 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 oral dosage units are as defined in  claim 45 , and wherein 7 or less of said oral dosage units contain ethinylestradiol alone in an amount from about 0.01 mg to about 0.05 mg. 
     
     
         56 . The preparation according to  claim 55 , wherein the number of oral dosage units is 21, 22, 23 or 24, and wherein the number of oral dosage units containing ethinylestradiol alone is 7, 6, 5 or 4. 
     
     
         57 . A pharmaceutical preparation comprising a number of separately packaged and individually removable oral dosage units as defined in  claim 46  placed in a packaging unit and intended for oral administration for a period of at least 21 consecutive days. 
     
     
         58 . The preparation according to  claim 57 , wherein the number of oral dosage units is 28, or a multiple of 28. 
     
     
         59 . The preparation according to  claim 58 , wherein the number of oral dosage units is 2 times 28, 3 times 38, or 4 times 28. 
     
     
         60 . The preparation according to  claim 57 , which additionally comprises 7 or less oral dosage units containing no active agent intended for oral administration subsequent to the period of at least 21 days, the total number of daily dosage units being at least 28. 
     
     
         61 . The preparation according to  claim 59 , wherein the number of oral dosage units is 21, 22, 23, or 24, and wherein the number of oral dosage units containing no active agent is 7, 6, 5 or 4. 
     
     
         62 . A pharmaceutical preparation comprising a number of separately packaged and individually removable oral 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 oral dosage units are as defined in  claim 46 , and wherein 7 or less of said oral dosage units contain ethinylestradiol alone in an amount from about 0.01 mg to about 0.05 mg. 
     
     
         63 . The preparation according to  claim 62 , wherein the number of oral dosage units is 21, 22, 23 or 24, and wherein the number of oral dosage units containing ethinylestradiol along is 7, 6, 5 or 4. 
     
     
         64 . A method for preparing a pharmaceutical composition as defined in  claim 36 , comprising spraying a solution of drospirenone onto the surface of inert carrier particles followed by incorporation of the particles in the composition. 
     
     
         65 . A method for preparing a pharmaceutical composition as defined in  claim 37 , comprising spraying a solution of drospirenone onto the surface of inert carrier particles and spraying a solution of ethinylestradiol onto the surface of inert carrier particles followed by incorporation of the particles in the composition.