Solid pharmaceutical compositions comprising biopterin derivatives and uses of such compositions

1. A method for preparing a lyophilized solid pharmaceutical composition comprising

a) a compound having the formula (I):

and/or a compound having the formula (II):

 and

b) two different sodium phosphate salts, wherein the two different sodium phosphate salts are NaH 2 PO 4 ·2H 2 O and Na 2 HPO 4 ·2H 2 O, and wherein the quantity of the NaH 2 PO 4 ·2H 2 O and Na 2 HPO 4 ·2H 2 O present in the composition is chosen such that the molar ratio of both NaH 2 PO 4 ·2H 2 O and Na 2 HPO 4 ·2H 2 O to compound (I) or compound (II) ranges from 0.02 to 0.5 and optionally NaCl;

the method comprising:

aa) dissolving the compound of the formula (III) and/or (II):

with a buffer,

wherein the buffer comprises the two different sodium phosphate salts, wherein the buffer is prepared by

separately dissolving in water NaH 2 PO 4 ·2H 2 O and Na 2 HPO 4 ·2H 2 O,

then adding the NaH 2 PO 4 ·2H 2 O solution to the Na 2 HPO 4 ·2H 2 O solution to obtain a sodium phosphate solution with a pH of 7.4, and

then adding the sodium phosphate solution to a 5N NaOH solution; and

bb) lyophilization of the solution obtained in aa).

2. The method of claim 1 , wherein the lyophilisate obtained in bb) is filled into a 50 ml vial.

3. The method of claim 2 , wherein the lyophilisate obtained in bb) is filled into a 50 ml vial

(i) in an amount of about 1-1.5 g; or

(ii) in an amount of about 0.9-1.4 g.

4. The method of claim 3 , wherein the buffer comprises 12-16% (w/w) NaOH 5N, 8-12% (w/w) sodium hydrogen phosphate buffer and 74-78% (w/w) water for injection.

5. The method of claim 1 , wherein the buffer comprises 12-16% (w/w) NaOH 5N, 8-12% (w/w) sodium hydrogen phosphate buffer and 74-78% (w/w) water for injection.

6. The method of claim 1 , wherein the solution obtained in aa) is sterile filtered.

7. The method of claim 1 , wherein buffer is prepared with degassed buffer.

8. The method of claim 7 , wherein buffer is degassed with nitrogen until the oxygen content is <1.0 ppm.

9. The method of claim 1 , wherein after the preparation of the solution, the lyophilisation is started at most 2 hours later.

10. The method of claim 3 , wherein the lyophilisate obtained in bb) is filled into a 50 ml vial for (i) in an amount of about 1.25 g solid formulation or for (ii) in an amount of 1.15 g solid formulation.

11. The method of claim 6 , wherein the solution obtained in aa) is sterile filtered with a 0.22 μm filter.