FAST DISSOLVING PHARMACEUTICAL COMPOSITIONS
The present disclosure relates to the field of pharmaceutical compositions. Furthermore, the present invention relates to an immediate release pharmaceutical composition in the form of a non-effervescent tablet composition comprising dasatinib and a gas generating agent.
1 . A method for reducing pleural effusion in a patient suffering from a proliferative disorder by administering a pharmaceutical composition comprising dasatinib as an amorphous solid dispersion, wherein the administered amount of dasatinib is 20% to 30% lower in intra-subject variability of Cmin than a dose required for delivering a therapeutically effective amount of dasatinib in the fasted state using a conventional crystalline dasatinib formulation.
2 . The method of claim 1 , wherein the pharmaceutical composition, comprises: (a) particles comprising (i) dasatinib in an amount of about 10% by weight to about 70% by weight of the particles; and (ii) at least one polymeric stabilizing and matrix-forming component.
3 . The method of claim 2 , wherein the pharmaceutical composition further comprises (b) at least one disintegrant agent in an amount of about 4% by weight to about 16% by weight; (c) at least one gas generating agent in an amount of about 8% by weight to about 22% by weight; and (d) at least one acidic pH modifier in an amount of about 2% by weight to about 6% by weight.
4 . The method of claim 2 , wherein the pharmaceutical composition further comprises (b) at least one disintegrant agent in an amount of about 4% by weight to about 16% by weight; (c) at least one gas generating agent in an amount of about 8% by weight to about 22% by weight; and (d) at least one acidic pH modifier in an amount of about 2% by weight to about 6% by weight and wherein the gas generating agent is selected from a group consisting of sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, sodium sulfite, potassium sulfite, an ammonium cation, and a combination thereof.
5 . The method of claim 2 , wherein the pharmaceutical composition further comprises (b) at least one disintegrant agent in an amount of about 4% by weight to about 16% by weight; (c) at least one gas generating agent in an amount of about 8% by weight to about 22% by weight; and (d) at least one acidic pH modifier in an amount of about 2% by weight to about 6% by weight and wherein the gas generating agent is selected from a group consisting of sodium bicarbonate, potassium bicarbonate, and a combination thereof.
6 . The method of claim 2 , wherein the pharmaceutical composition further comprises (b) at least one disintegrant agent in an amount of about 4% by weight to about 16% by weight; (c) at least one gas generating agent in an amount of about 8% by weight to about 22% by weight; and (d) at least one acidic pH modifier in an amount of about 2% by weight to about 6% by weight and wherein the acidic pH modifier is selected from a group consisting of sorbic acid, adipic acid, succinic acid, fumaric acid, tartaric acid, and a combination thereof.
7 . The method of claim 3 , wherein the mole ratio of the gas generating agent to the acidic pH-modifier ranges from about 4:1 to about 1:4.
8 . The method of claim 3 , wherein the disintegrating agent comprises crospovidone.
9 . The method of claim 1 , wherein the pharmaceutical composition comprises dasatinib in an amount of about 15 mg, about 36 mg, about 50 mg, about 57 mg, about 70 mg, or about 100 mg.
10 . The method of claim 1 , where the proliferative disorder is selected from newly diagnosed adults with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase; adults with chronic, accelerated, or myeloid or lymphoid blast phase Ph+ CML with resistance or intolerance to prior therapy including imatinib; and adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) with resistance or intolerance to prior therapy.
11 . A method for reducing pleural effusion in a patient suffering from a proliferative disorder by administering a pharmaceutical composition comprising dasatinib as an amorphous solid dispersion, wherein the administered amount of dasatinib is 20% to 30% less than a dose required for delivering a therapeutically effective amount of dasatinib in the fasted state using a conventional crystalline dasatinib formulation.
12 . The method of claim 11 , wherein the pharmaceutical composition, comprises: (a) particles comprising (i) dasatinib in an amount of about 10% by weight to about 70% by weight of the particles; and (ii) at least one polymeric stabilizing and matrix-forming component.
13 . The method of claim 12 , wherein the pharmaceutical composition further comprises (b) at least one disintegrant agent in an amount of about 4% by weight to about 16% by weight; (c) at least one gas generating agent in an amount of about 8% by weight to about 22% by weight; and (d) at least one acidic pH modifier in an amount of about 2% by weight to about 6% by weight.
14 . The method of claim 12 , wherein the pharmaceutical composition further comprises (b) at least one disintegrant agent in an amount of about 4% by weight to about 16% by weight; (c) at least one gas generating agent in an amount of about 8% by weight to about 22% by weight; and (d) at least one acidic pH modifier in an amount of about 2% by weight to about 6% by weight and wherein the gas generating agent is selected from a group consisting of sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, sodium sulfite, potassium sulfite, an ammonium cation, and a combination thereof.
15 . The method of claim 12 , wherein the pharmaceutical composition further comprises (b) at least one disintegrant agent in an amount of about 4% by weight to about 16% by weight; (c) at least one gas generating agent in an amount of about 8% by weight to about 22% by weight; and (d) at least one acidic pH modifier in an amount of about 2% by weight to about 6% by weight and wherein the gas generating agent is selected from a group consisting of sodium bicarbonate, potassium bicarbonate, and a combination thereof.
16 . The method of claim 12 , wherein the pharmaceutical composition further comprises (b) at least one disintegrant agent in an amount of about 4% by weight to about 16% by weight; (c) at least one gas generating agent in an amount of about 8% by weight to about 22% by weight; and (d) at least one acidic pH modifier in an amount of about 2% by weight to about 6% by weight and wherein the acidic pH modifier is selected from a group consisting of sorbic acid, adipic acid, succinic acid, fumaric acid, tartaric acid, and a combination thereof.
17 . The method of claim 13 , wherein the mole ratio of the gas generating agent to the acidic pH-modifier ranges from about 4:1 to about 1:4.
18 . The method of claim 13 , wherein the disintegrating agent comprises crospovidone.
19 . The method of claim 11 , wherein the pharmaceutical composition comprises dasatinib in an amount of about 15 mg, about 36 mg, about 50 mg, about 57 mg, about 70 mg, or about 100 mg.
20 . The method of claim 11 , where the proliferative disorder is selected from newly diagnosed adults with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase; adults with chronic, accelerated, or myeloid or lymphoid blast phase Ph+ CML with resistance or intolerance to prior therapy including imatinib; and adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) with resistance or intolerance to prior therapy.