Pharmaceutical formulations

Abstract

The invention provides a solid oral dosage form comprising tenofovir alafenamide or a pharmaceutically acceptable salt thereof, and emtricitabine or a pharmaceutically acceptable salt thereof.

1 . A solid oral dosage form comprising tenofovir alafenamide or a pharmaceutically acceptable salt thereof and emtricitabine or a pharmaceutically acceptable salt thereof. 
     
     
         2 . The solid oral dosage form of  claim 1 , wherein the dosage form is substantially free of rilpivirine or a pharmaceutically acceptable salt thereof. 
     
     
         3 . A solid composition comprising tenofovir alafenamide or a pharmaceutically acceptable salt thereof wherein the proportion of tenofovir alafenamide or a pharmaceutically acceptable salt thereof in the composition is from about 2.5% to about 12% by weight. 
     
     
         4 . The solid composition of  claim 3 , wherein the proportion of tenofovir alafenamide or a pharmaceutically acceptable salt thereof in the composition is from about 4% to about 12% by weight. 
     
     
         5 . A solid composition comprising from about 2% to about 4% by weight tenofovir alafenamide hemifumarate. 
     
     
         6 . A solid composition comprising from about 5% to about 15% by weight tenofovir alafenamide hemifumarate. 
     
     
         7 . The solid oral dosage form or composition of any one of the preceding claims, wherein the dosage form or composition is a tablet. 
     
     
         8 . The tablet according to  claim 7 , wherein the total weight of the tablet is about 350 mg. 
     
     
         9 . The tablet according to  claim 7 , wherein the total weight of the tablet is 350 mg. 
     
     
         10 . The tablet according to any one of  claims 7 - 9 , wherein the tablet is coated with a film coating. 
     
     
         11 . The tablet according  claim 10 , wherein the film coating comprises Opadry II 
     
     
         12 . The tablet according to  claim 10  or  claim 11 , wherein the amount of the coating is 2-4% by weight of the core of the tablet. 
     
     
         13 . The tablet according to any one of  claims 10 - 12 , wherein the amount of the coating is about 3% of the weight of the core of the tablet. 
     
     
         14 . The tablet according to any one of  claims 7 - 9 , wherein the total weight of the tablet is 360.5 mg. 
     
     
         15 . The tablet according to any one of  claims 7 - 9 , wherein over 40% by weight of the tablet is emtricitabine or a pharmaceutically acceptable salt thereof and tenofovir alafenamide or a pharmaceutically acceptable salt thereof. 
     
     
         16 . The tablet according to any one of  claims 7 - 9 , wherein over 60% by weight of the tablet is emtricitabine or a pharmaceutically acceptable salt thereof and tenofovir alafenamide or a pharmaceutically acceptable salt thereof. 
     
     
         17 . The tablet according to  claim 16 , wherein over 60% by weight of the tablet is emtricitabine and tenofovir alafenamide hemifumarate. 
     
     
         18 . The tablet according to any of  claims 10 - 14  wherein over 40% by weight of the tablet is emtricitabine or a pharmaceutically acceptable salt thereof and tenofovir alafenamide or a pharmaceutically acceptable salt thereof. 
     
     
         19 . The tablet according to any of  claims 10 - 14 , wherein over 58% by weight of the tablet is emtricitabine or a pharmaceutically acceptable salt thereof and tenofovir alafenamide or a pharmaceutically acceptable salt thereof. 
     
     
         20 . The tablet according to  claim 19 , wherein over 58% by weight of the tablet is emtricitabine and tenofovir alafenamide hemifumarate. 
     
     
         21 . The tablet according to any one of  claims 7 - 9 , comprising 200 mg emtricitabine and 11.2 mg tenofovir alafenamide hemifumarate, wherein at least 50% of the total weight of the tablet is emtricitabine and tenofovir alafenamide hemifumarate. 
     
     
         22 . The tablet according to any one of  claims 10 - 14 , comprising 200 mg emtricitabine and 11.2 mg tenofovir alafenamide hemifumarate, wherein at least 50% of the total weight of the tablet is emtricitabine and tenofovir alafenamide hemifumarate. 
     
     
         23 . The tablet according to any one of  claims 7 - 9 , comprising 200 mg emtricitabine and 28 mg tenofovir alafenamide hemifumarate, wherein at least 50% of the total weight of the tablet is emtricitabine and tenofovir alafenamide hemifumarate. 
     
     
         24 . The tablet according to any one of  claims 10 - 14 , comprising 200 mg emtricitabine and 28 mg tenofovir alafenamide hemifumarate, wherein at least 50% of the total weight of the tablet is emtricitabine and tenofovir alafenamide hemifumarate. 
     
     
         25 . A composition comprising (a) tenofovir alafenamide or a pharmaceutically acceptable salt thereof, and (b) emtricitabine or a pharmaceutically acceptable salt thereof, where the total quantity of degradation products derived from the tenofovir alafenamide or the pharmaceutically acceptable salt thereof is less than 3% after storage for one month at 40° C./75% RH in open conditions. 
     
     
         26 . A composition comprising (a) tenofovir alafenamide or a pharmaceutically acceptable salt thereof, and (b) emtricitabine or a pharmaceutically acceptable salt thereof, where the total quantity of degradation products derived from the tenofovir alafenamide or the pharmaceutically acceptable salt thereof is less than 2.5% after storage for three months at 40° C./75% RH in closed conditions. 
     
     
         27 . A composition comprising (a) tenofovir alafenamide or a pharmaceutically acceptable salt thereof, and (b) emtricitabine or a pharmaceutically acceptable salt thereof, where the total quantity of degradation products derived from the tenofovir alafenamide or the pharmaceutically acceptable salt thereof is less than 2% after storage for twelve months at 30° C./75% RH in closed conditions. 
     
     
         28 . The compositions according to any one of  claims 25 - 27 , wherein the composition is a tablet. 
     
     
         29 . The tablet according to  claim 28  comprising 7-9% by weight tenofovir alafenamide hemifumarate, preferably about 8% by weight tenofovir alafenamide hemifumarate, wherein the total quantity of degradation products derived from the tenofovir alafenamide hemifumarate is less than about 2%, preferably about 1.7%, after storage for 3 months at 40° C./75% RH in closed conditions. 
     
     
         30 . The tablet according to  claim 29  comprising about 8% by weight tenofovir alafenamide hemifumarate and further comprising at least 55% by weight emtricitabine. 
     
     
         31 . The tablet according to  claim 28  comprising about 3-4% by weight tenofovir alafenamide hemifumarate, preferably about 3% by weight tenofovir alafenamide hemifumarate, wherein the total quantity of degradation products derived from the tenofovir alafenamide hemifumarate is less than about 2.5%, preferably about 1.8%, after storage for 3 months at 40° C./75% RH in closed conditions. 
     
     
         32 . The tablet according to  claim 31  comprising about 3% by weight tenofovir alafenamide hemifumarate and at least 55% by weight emtricitabine. 
     
     
         33 . The tablet according to  claim 28  wherein said tablet comprises tenofovir alafenamide hemifumarate and emtricitabine and the total quantity of degradation products derived from the tenofovir alafenamide hemifumarate is less than about 2% after storage for 12 months at 30° C./75% RH in closed conditions. 
     
     
         34 . The tablet according to  claim 33  comprising 7-9% by weight tenofovir alafenamide hemifumarate, preferably about 8% by weight tenofovir alafenamide hemifumarate, wherein the total quantity of degradation products derived from the tenofovir alafenamide hemifumarate is less than about 2%, preferably less than 1%, after storage for 12 months at 30° C./75% RH in closed conditions. 
     
     
         35 . The tablet according to  claim 34  comprising about 8% by weight tenofovir alafenamide hemifumarate and further comprising at least 55% by weight emtricitabine. 
     
     
         36 . The tablet according to  claim 33  comprising about 3-4% by weight tenofovir alafenamide hemifumarate, preferably about 3% by weight tenofovir alafenamide hemifumarate, wherein the total quantity of degradation products derived from the tenofovir alafenamide hemifumarate is less than about 2%, preferably less than 1.5% after storage for 12 months at 30° C./75% RH in closed conditions. 
     
     
         37 . The tablet according to  claim 36  comprising about 3% by weight tenofovir alafenamide hemifumarate and at least 55% by weight emtricitabine. 
     
     
         38 . The solid oral dosage form, the composition, or the tablet according to any one of  claims 1 - 37 , wherein the solid oral dosage form, the composition, or the tablet comprises excipients which consist of croscarmellose sodium, microcrystalline cellulose and magnesium stearate. 
     
     
         39 . The solid oral dosage form, the composition, or the tablet according to any one of  claims 1 - 37 , wherein the solid oral dosage form, the composition, or the tablet comprises 150-250 mg emtricitabine or a salt thereof, 5-35 mg tenofovir alafenamide or a salt thereof, 20-35 mg croscarmellose sodium, 70-120 mg microcrystalline cellulose and 1-7 mg magnesium stearate. 
     
     
         40 . The solid oral dosage form, the composition, or the tablet according to  claim 39 , wherein the solid oral dosage form, the composition, or the tablet comprises 200 mg emtricitabine, 11.2 mg tenofovir alafenamide hemifumarate, 28 mg croscarmellose sodium, 105.56 microcrystalline cellulose, 5.25 mg magnesium stearate and a film coating consisting of Opadry II Gray 85F97517. 
     
     
         41 . The solid oral dosage form, the composition, or the tablet according to  claim 39 , wherein the solid oral dosage form, the composition, or the tablet comprises 200 mg emtricitabine, 28 mg tenofovir alafenamide hemifumarate, 28 mg croscarmellose sodium, 88.70 mg microcrystalline cellulose, 5.25 mg magnesium stearate and a film coating consisting of Opadry II Blue 85F105057. 
     
     
         42 . A kit comprising a) the tablet according to any one of  claims 1 - 41  and b) a dessicant, preferably wherein said dessicant is silica gel. 
     
     
         43 . A method of producing a solid oral dosage form, composition or tablet of any one of the preceding claims. 
     
     
         44 . A dry granulated mixture of (a) tenofovir alafenamide or a pharmaceutically acceptable salt thereof, and (b) emtricitabine or a pharmaceutically acceptable salt thereof. 
     
     
         45 . A solid oral dosage form, composition or tablet according to any one of the preceding claims for use in the therapeutic treatment of an HIV infection. 
     
     
         46 . A method of therapeutic treatment of an HIV infection comprising administering to a subject a solid oral dosage form, composition or tablet according to any one of the preceding claims. 
     
     
         47 . A method of preventing HIV infection comprising administering to a subject a solid oral dosage form, composition or tablet according to any one of the preceding claims. 
     
     
         48 . The method of  claim 46 , wherein the solid oral dosage form, composition or tablet is administered at an interval of less than once daily. 
     
     
         49 . The method of  claim 47  or  claim 48 , wherein the solid oral dosage form, composition or tablet is administered prior to and following an event that would increase the individual's risk of acquiring HIV.