Pharmaceutical compositions comprising prasugrel and cyclodextrin derivatives and methods of making and using the same

1. A pharmaceutical composition comprising:

prasugrel, and

a cyclodextrin derivative of Formula I:

wherein n is 4, 5 or 6;

R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 and R 9 are independently selected from: —OH, a straight-chain or branched —O—(C 1 -C 8 -(alkylene))-SO 3 − group, a substituted or unsubstituted straight-chain, branched, or cyclic —O—(C 1 -C 10 ) group, a substituted straight-chain, branched, or cyclic —S—(C 1 -C 10 ) group, and a saccharide;

wherein the composition is formulated for oral administration; and

wherein the cyclodextrin derivative is present in a concentration of at least 50:1 by mole relative to the prasugrel.

2. The pharmaceutical composition of claim 1 , further comprising at least one pharmaceutically acceptable excipient.

3. The pharmaceutical composition of claim 1 , wherein the bioavailability of the prasugrel in the composition is greater than an eqiumolar amount of prasugrel alone.

4. The pharmaceutical composition of claim 1 , wherein the time to therapeutic onset of prasugrel is reduced by at least 20%.

5. The pharmaceutical composition of claim 1 , wherein the cyclodextrin derivative is present in a concentration of at least 100:1 by mole relative to the prasugrel.

6. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition has a pH of 2 to 4.

7. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition has a pH of 4 to 9.

8. A pharmaceutical composition comprising

prasugrel, and

a cyclodextrin derivative of Formula I:

wherein n is 4, 5 or 6;

R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 and R 9 are independently selected from: —OH, a straight-chain or branched —O—(C 1 -C 8 -(alkylene))-SO 3 − group, a substituted or unsubstituted straight-chain, branched, or cyclic —O—(C 1 -C 10 ) group, a substituted straight-chain, branched, or cyclic —S—(C 1 -C 10 ) group, and a saccharide;

wherein the composition is formulated for oral or parenteral administration; and

wherein the cyclodextrin derivative is present in a concentration of at least 50:1 by mole relative to the prasugrel.

9. The pharmaceutical composition of claim 8 , wherein at least one of R 1 , R 2 , R 3 , R 4 , R 5 , R 4 , R 7 , R 8 and R 9 is a —O-(hydroxy-substituted-C 3 ) group.

10. The pharmaceutical composition of claim 8 , wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 and R 9 are independently OH or a straight-chain or branched —O—(C 1 -C 8 -(alkylene))-SO 3 − group, and wherein the degree of substitution with a straight-chain or branched —O—(C 1 -C 8 -(alkylene))-SO 3 − group is 4 to 8 per cyclodextrin derivative.

11. The pharmaceutical composition of claim 8 , wherein at least one of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 and R 9 is substituted with a —O-(straight-chain C4-(alkylene))-SO 3 − group.

12. The pharmaceutical composition of claim 8 , wherein the cyclodextrin derivative is a compound of formula II:

wherein R=(H) 21-x or (—(CH 2 ) 4 —SO 3 − Na + ) x , and wherein x=6.0-7.1.

13. The pharmaceutical composition of claim 12 , comprising an agent selected from: a carrier, a diluent, a preservative, an antioxidant, a second therapeutic agent, an acidifying agent, an alkalinizing agent, a buffering agent, a bulking agent, a complexation enhancing agent, a cryoprotectant, a density modifier, an electrolyte, a flavor, a fragrance, a lyophilizing aid, a plasticizer, a solubility-enhancing agent, a stabilizing agent, a surface tension modifier, a volatility modifier, a viscosity modifier, and combinations thereof.

14. The pharmaceutical composition of claim 12 , further comprising a sweetener.

15. The pharmaceutical composition of claim 12 , wherein the composition is selected from the group consisting of a solution, a suspension, and an emulsion.

16. The pharmaceutical composition of claim 12 , wherein the composition further comprises 1 mg to 120 mg of prasugrel.

17. A method of treating a disease, disorder or condition having an etiology associated with platelet aggregation or of a disease, disorder or condition that is therapeutically responsive to prasugrel, comprising administering a pharmaceutical composition according to claim 1 to a subject in need thereof.

18. The method of claim 17 , wherein the composition is administered as a unit dosage form comprising a maintenance dose of 1 mg to 20 mg of prasugrel.

19. The method of claim 17 , wherein the composition is administered as a unit dosage form comprising a loading dose comprising 20 mg to 120 mg of prasugrel.

20. The method of claim 17 , wherein the disorder is selected from: an acute coronary syndrome, a recent myocardial infarction, a recent stroke, an established peripheral arterial disease, ST-segment elevation acute myocardial infarction, non-ST-segment elevation acute coronary syndrome, a recent percutaneous coronary intervention, a recent angioplasty, a thromboembolism, a pulmonary embolism, a deep vein thrombosis, atherosclerosis, diabetes mellitus, a transient ischemic event, a secondary ischemic event, vascular death with established peripheral arterial disease, cardiovascular disease, cerebrovascular disease, angina pectoris, cardiac arrhythmia, sickle cell crisis, and combinations thereof.