Orodispersible formulations

Abstract

An orodispersible formulation for contraception or hormone replacement therapy containing an estrogen and a progestogen that has sufficient hardness, disintegration time and friability.

1 . An orodispersible solid dosage form, comprising:
 a first active ingredient in amount of up to about 0.5% w/w of the dosage form;   an intragranular component; and   an extragranular component,   wherein the intragranular component comprises:
 at least one intragranular diluent; 
 at least one intragranular disintegrant; and 
 at least one intragranular binder, 
   wherein the extragranular component comprises:
 at least one extragranular diluent; and 
 at least one extragranular disintegrant, 
   wherein the intragranular component constitutes from about 40% w/w to about 80% w/w of the orodispersible solid dosage form,   wherein an intragranular diluent content is from about 80% w/w to about 97% w/w of the intragranular component,   wherein an intragranular disintegrant content is from about 2% w/w to about 5% w/w of the intragranular component,   wherein an intragranular binder content is from about 0.2% w/w to about 7% w/w of the intragranular component,   wherein an extragranular diluent content is from about 70% w/w to about 88% w/w of the extragranular component,   wherein an extragranular disintegrant content is from about 4% w/w to about 12% w/w of the extragranular component, and   wherein the orodispersible solid dosage form disintegrates in about 60 seconds or less.   
     
     
         2 . The orodispersible solid dosage form of  claim 1 , wherein the intragranular disintegrant content in the intragranular component is lower than the extragranular disintegrant content in the extragranular component. 
     
     
         3 . The orodispersible solid dosage form of  claim 1 , wherein the extragranular component further comprises at least one extragranular binder. 
     
     
         4 . The orodispersible solid dosage form of  claim 3 , wherein an extragranular binder content is from about 3% w/w to about 12% w/w of the extragranular component. 
     
     
         5 - 15 . (canceled) 
     
     
         16 . The orodispersible solid dosage form of  claim 1 , wherein the at least one intragranular diluent and/or the at least one extragranular diluent is selected from the group consisting of microcrystalline cellulose, glucose, dextrose, fructose, lactose, mannitol, sorbitol and combinations thereof. 
     
     
         17 . The orodispersible solid dosage form of  claim 1 , wherein the at least one intragranular disintegrant and/or the at least one extragranular disintegrant is selected from the group consisting of croscarmellose sodium, sodium starch glycolate, crospovidone, and combinations thereof. 
     
     
         18 . The orodispersible solid dosage form of  claim 1 , wherein the at least one intragranular binder and/or the extragranular binder is selected from the group consisting of a starch, a partially pregelatinized starch, a fully pregelatinized starch, povidone, and combinations thereof. 
     
     
         19 . The orodispersible solid dosage form of  claim 1 , wherein the orodispersible solid dosage form is about 70 mg to about 90 mg. 
     
     
         20 . (canceled) 
     
     
         21 . The orodispersible solid dosage form of  claim 1 , wherein the orodispersible solid dosage form has a hardness from about 2 kP to about 7 kP. 
     
     
         22 . The orodispersible solid dosage form of  claim 1 , wherein the orodispersible solid dosage form has a friability of 0.3% or less. 
     
     
         23 . (canceled) 
     
     
         24 . The orodispersible solid dosage form of  claim 1 , wherein the first active ingredient is an estrogen. 
     
     
         25 . The orodispersible solid dosage form of  claim 24 , wherein the estrogen is selected from the group consisting of ethinyl estradiol, 17β-estradiol, 17β-estradiol-3-acetate, mestranol, conjugated estrogens, USP and estrone, and any salts or combinations thereof. 
     
     
         26 . The orodispersible solid dosage form of  claim 24  further comprising a second active ingredient, wherein said second active ingredient is a progestogen. 
     
     
         27 . The orodispersible solid dosage form of  claim 26 , wherein the progestogen is selected from the group consisting of 17-hydroxy progesterone esters and 19-nor-17-hydroxy progesterone esters, 17-alpha-ethinyl testosterone, 17-alpha-ethinyl-19-nortestosterone (norethindrone) and derivatives thereof, norethindrone acetate, norgestrel, nogestamate, desogestrel and D-17-beta-acetoxy-17-beta-ethyl-17-alpha-ethinyl-gon-4-en-3-one oxime, and combinations thereof. 
     
     
         28 . An orodispersible solid dosage form, comprising:
 a first active ingredient in amount of up to about 0.5% w/w of the dosage form;   at least one diluent, where a diluent content is about 80 to about 95% w/w of the orodispersible solid dosage form;   at least one binder, where a binder content is about 2 to about 7% w/w of the orodispersible solid dosage form; and   at least one disintegrant, where a disintegrant content is about 2 to about 8% w/w of the orodispersible solid dosage form,   wherein the orodispersible solid dosage form has an intragranular component and an extragranular component,   wherein the intragranular component constitutes from about 40% w/w to about 80% w/w of the orodispersible solid dosage form,   wherein the intragranular component comprises the least one diluent, the at least one disintegrant, and the at least one binder,   wherein the extragranular component comprises the at least one diluent and the at least one disintegrant, and   orodispersible solid dosage form disintegrates in about 60 seconds or less.   
     
     
         29 . The orodispersible solid dosage form of  claim 28 , wherein the extragranular component further comprises at least one binder. 
     
     
         30 . The orodispersible solid dosage form of  claim 28 , wherein the diluent content is about 82% w/w to about 93% w/w of the orodispersible solid dosage form. 
     
     
         31 . The orodispersible solid dosage form of  claim 28 , wherein the disintegrant content is about 3% w/w to about 8% w/w of the orodispersible solid dosage form. 
     
     
         32 . The orodispersible solid dosage form of any of  claim 28 , wherein the binder content is about 3% w/w to about 8% w/w of the orodispersible solid dosage form. 
     
     
         33 . The orodispersible solid dosage form of  claim 28 , wherein the at least one diluent is selected from the group consisting of microcrystalline cellulose, glucose, dextrose, fructose, lactose, mannitol, sorbitol and combinations thereof. 
     
     
         34 . The orodispersible solid dosage form of  claim 28 , wherein the at least one disintegrant is selected from the group consisting of croscarmellose sodium, sodium starch glycolate, crospovidone, and combinations thereof. 
     
     
         35 . The orodispersible solid dosage form of  claim 28 , wherein the at least one binder is selected from the group consisting of a starch, a partially pregelatinized starch, a fully pregelatinized starch, povidone, and combinations thereof. 
     
     
         36 . The orodispersible solid dosage form of  claim 28 , wherein the dosage form is about 70 mg to about 90 mg. 
     
     
         37 . (canceled) 
     
     
         38 . The orodispersible solid dosage form of  claim 28 , wherein the orodispersible solid dosage has a hardness from about 2 kP to about 7 kP. 
     
     
         39 . The orodispersible solid dosage form of  claim 28 , wherein the orodispersible solid dosage has a friability of 0.3% or less. 
     
     
         40 . (canceled) 
     
     
         41 . The orodispersible solid dosage form of  claim 28 , wherein the first active ingredient is an estrogen. 
     
     
         42 . The orodispersible solid dosage form of  claim 41 , wherein the estrogen is selected from the group consisting of ethinyl estradiol, 17β-estradiol, 17β-estradiol-3-acetate, mestranol, conjugated estrogens, USP and estrone, and any salts or combinations thereof. 
     
     
         43 . The orodispersible solid dosage form of  claim 41  further comprising a second active ingredient, wherein said second active ingredient is a progestogen. 
     
     
         44 . The orodispersible solid dosage form of  claim 43 , wherein the progestogen is selected from the group consisting of 17-hydroxy progesterone esters and 19-nor-17-hydroxy progesterone esters, 17-alpha-ethinyl testosterone, 17-alpha-ethinyl-19-nortestosterone (norethindrone) and derivatives thereof, norethindrone acetate, norgestrel, nogestamate, desogestrel and D-17-beta-acetoxy-17-beta-ethyl-17-alpha-ethinyl-gon-4-en-3-one oxime, and combinations thereof. 
     
     
         45 - 51 . (canceled) 
     
     
         52 . A method of contraception and/or hormone replacement therapy, comprising administering the orodispersible solid dosage form of  claim 1  to a female in need thereof. 
     
     
         53 . The method of  claim 52 , wherein the orodispersible solid dosage form is administered sublingually, buccally or sublabially. 
     
     
         54 - 64 . (canceled) 
     
     
         65 . A method of increasing oral absorption of ethinyl estradiol into and/or through the oral mucosa, comprising orally administering the orodispersible solid dosage form of  claim 41 . 
     
     
         66 . The method of  claim 65 , wherein the orodispersible solid dosage form is administered sublingually, buccally, or sublabially. 
     
     
         67 . The method of  claim 65 , wherein the orodispersible solid dosage form is placed on the tongue. 
     
     
         68 . The method of  claim 65 , wherein at least 90% of ethinyl estradiol in the orodispersible solid dosage form is absorbed into and/or through the oral mucosa and/or tongue. 
     
     
         69 - 73 . (canceled)