Pharmaceutical compositions comprising active drugs, contraceptive kits comprising active drugs, and methods of administering the same

Abstract

The present invention relates to pharmaceutical compositions and kits comprising pharmaceutical compositions, and methods for administering pharmaceutical compositions comprising active contraceptive drugs in a patient. Specifically, the pharmaceutical compositions may comprise progestogen-only contraceptives (“POC”), such as Drospirenone.

1 - 168 . (canceled) 
     
     
         169 - 189 . (canceled) 
     
     
         190 . A pharmaceutical composition comprising:
 a single daily progestogen-only contraceptive, formulated in a solid form for oral administration to a patient;   wherein the progestogen-only contraceptive comprises about 2 mg to about 6 mg drospirenone and one or more pharmaceutically-acceptable excipients;   wherein said excipients comprise a binder, a filler, a glidant, and a lubricant;   wherein the dissolution rate of said drospirenone in said pharmaceutical composition is such that when subjected to an in vitro dissolution test according to the USP XXIII Paddle Method: no more than 50% of said drospirenone initially present in said pharmaceutical composition is dissolved within 30 minutes; and   wherein said pharmaceutical composition does not include an estrogen.   
     
     
         191 . The pharmaceutical composition of  claim 190 , wherein said binder is selected from one or more of the following: starches, gums, microcrystalline cellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, hydroxypropylmethyl cellulose, and polyvinyl pyrrolidone. 
     
     
         192 . The pharmaceutical composition of  claim 190 , wherein said filler is selected from one or more of the following: lactose anhydrous, microcrystalline cellulose, starch, pregelatinized starch, modified starch, dibasic calcium phosphate dihydrate, calcium sulfate trihydrate, calcium sulfate dihydrate, calcium carbonate, lactose, dextrose, sucrose, mannitol, and sorbitol. 
     
     
         193 . The pharmaceutical composition of  claim 190 , wherein said glidant is selected from one or more of the following: silicon dioxide, magnesium trisilicate, powdered cellulose, starch, talc and tribasic calcium phosphate. 
     
     
         194 . The pharmaceutical composition of  claim 190 , wherein said lubricant is selected from one or more of the following: magnesium stearate, calcium stearate, zinc stearate, talc, propylene glycol, PEG, stearic acid, vegetable oil, sodium benzoate, sodium lauryl sulfate, magnesium lauryl sulfate, and mineral oil polyoxyethylene monostearate. 
     
     
         195 . The pharmaceutical composition of  claim 190 , wherein said drospirenone is provided in a particle form. 
     
     
         196 . The pharmaceutical composition of  claim 195 , wherein said drospirenone particles are obtained by a process consisting of: milling, crystallization, precipitation, sieve, or a combination thereof. 
     
     
         197 . The pharmaceutical composition of  claim 196 , wherein said milling process comprises subjecting said drospirenone to one or more mills selected from the group consisting of: a fluid energy mill, a ball mill, a rod mill, a hammer mill, a cutting mill, and an oscillating granulator. 
     
     
         198 . The pharmaceutical composition of  claim 195 , wherein said drospirenone particles have a size distribution characterized by a d 50  particle size in the range of about 10 μm to about 60 μm. 
     
     
         199 . The pharmaceutical composition of  claim 190 , wherein said drospirenone is provided in an amount of about 4 mg. 
     
     
         200 . The pharmaceutical composition of  claim 190 , wherein said active pharmaceutical composition tablets further comprise a coating comprising a film-forming agent and one or more suitable excipients. 
     
     
         201 . The pharmaceutical composition of  claim 200 , wherein said one or more suitable excipients of said coating are selected from the group consisting of: softeners, fillers, and colorants. 
     
     
         202 . The pharmaceutical composition of  claim 190 , wherein said pharmaceutical composition exhibits improved pharmacokinetics as compared to combined oral contraceptives containing drospirenone. 
     
     
         203 . The pharmaceutical composition of  claim 202 , wherein said improved pharmacokinetics comprises one or more of the following: a delayed mean T max , a reduced mean C max , and a reduced mean AUC oh-tlast . 
     
     
         204 . The pharmaceutical composition of  claim 190 , wherein said pharmacokinetic profile improves the tolerance of said drospirenone as compared to combined oral contraceptives containing drospirenone. 
     
     
         205 . The pharmaceutical composition of  claim 204 , wherein said improved tolerance comprises a reduction in side-effects comprising one or more of the following: hyperkalemia, spotting, and irregular bleeding. 
     
     
         206 . The pharmaceutical composition of  claim 190 , wherein said pharmacokinetic profile improves said patient's bleeding profile as compared to conventional progestogen-only contraceptives. 
     
     
         207 . The pharmaceutical composition of  claim 206 , wherein said improved bleeding profile comprises a reduction in the incidence of unscheduled spotting and bleeding. 
     
     
         208 . A pharmaceutical composition comprising:
 a single daily progestogen-only contraceptive, formulated in a solid form for oral administration to a patient;   wherein the progestogen-only contraceptive comprises about 2 mg to about 6 mg drospirenone and one or more pharmaceutically-acceptable excipients;   wherein said excipients comprise a binder, a filler, a glidant, and a lubricant;   wherein said pharmaceutical composition, when orally administered to said patient under fasting conditions, provides a pharmacokinetic profile for drospirenone comprising:
 (i) a mean T max  ranging from about 2.2 hours to about 6 hours; and 
 (ii) a mean C max  which is less than about 30 ng/ml; and 
   wherein said pharmaceutical composition does not include an estrogen.   
     
     
         209 . The pharmaceutical composition of  claim 208 , wherein said binder is selected from one or more of the following: starches, gums, microcrystalline cellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, hydroxypropylmethyl cellulose, and polyvinyl pyrrolidone. 
     
     
         210 . The pharmaceutical composition of  claim 208 , wherein said filler is selected from one or more of the following: lactose anhydrous, microcrystalline cellulose, starch, pregelatinized starch, modified starch, dibasic calcium phosphate dihydrate, calcium sulfate trihydrate, calcium sulfate dihydrate, calcium carbonate, lactose, dextrose, sucrose, mannitol, and sorbitol. 
     
     
         211 . The pharmaceutical composition of  claim 208 , wherein said glidant is selected from one or more of the following: silicon dioxide, magnesium trisilicate, powdered cellulose, starch, talc and tribasic calcium phosphate. 
     
     
         212 . The pharmaceutical composition of  claim 208 , wherein said lubricant is selected from one or more of the following: magnesium stearate, calcium stearate, zinc stearate, talc, propylene glycol, PEG, stearic acid, vegetable oil, sodium benzoate, sodium lauryl sulfate, magnesium lauryl sulfate, and mineral oil polyoxyethylene monostearate. 
     
     
         213 . The pharmaceutical composition of  claim 208 , wherein said drospirenone is provided in an amount of about 4 mg. 
     
     
         214 . The pharmaceutical composition of  claim 208 , wherein said pharmacokinetic profile for said drospirenone additionally comprises an AUC 0h-tlast  which is at least 300 ng·h/ml. 
     
     
         215 . The pharmaceutical composition of  claim 208 , wherein said active pharmaceutical composition tablets further comprise a coating comprising a film-forming agent and one or more suitable excipients. 
     
     
         216 . The pharmaceutical composition of  claim 215 , wherein said one or more suitable excipients of said coating are selected from the group consisting of: softeners, fillers, and colorants.