Crystalline molecular comlpexes of tadalafil
Crystalline molecular complexes of tadalafil are disclosed. The crystalline molecular complexes include those of tadalafil and oxalic acid, tadalafil and 4-hydroxybenzoic acid, tadalafil and 3-phenylpropanoic acid, tadalafil and malonic acid, tadalafil and methylparaben, and tadalafil and propylparaben. Pharmaceutical compositions containing the crystalline molecular complexes are also disclosed.
1. A crystalline molecular complex of tadalafil comprising tadalafil and a propylparaben co-former.
2. A crystalline molecular complex of tadalafil and propylparaben according to claim 1 where the molar ratio of the tadalafil and the propylparaben in the molecular complex is 1:1.
3. A crystalline molecular complex of tadalafil and propylparaben according to claim 1 , wherein the molecular complex is characterized by at least one of the following:
an X-ray powder diffractogram in accordance with FIG. 11 ; or
a Fourier transform infrared spectrum in accordance with FIG. 12 .
4. A crystalline molecular complex of tadalafil and propylparaben of claim 1 , wherein the molecular complex is characterized by: an X-ray powder diffractogram having peaks at 5.2, 10.5, 15.3, 18.7, 20.6, 22.0, and 24.5 °2θ±0.2 °2θ; an infrared spectrum having peaks at 747, 1098, 1271, 1433, 1645, 1700, and 3338 cm −1 ±cm −1 ; or both.
5. A pharmaceutical composition comprising a crystalline molecular complex of tadalafil and propylparaben of claim 4 and a pharmaceutically acceptable carrier.
6. A pharmaceutical composition comprising a crystalline molecular complex of tadalafil and propylparaben of claim 1 and a pharmaceutically acceptable carrier.
7. A method for making a crystalline molecular complex of tadalafil and propylparaben according to claim 1 , comprising the steps of:
grinding tadalafil and propylparaben; and
adding acetonitrile to the ground tadalafil and propylparaben.
8. A method for making a crystalline molecular complex of tadalafil and propylparaben according to claim 1 , comprising the steps of:
slurrying tadalafil, propylparaben, and acetonitrile; and
drying the slurried tadalafil, propylparaben, and acetonitrile.