Safe and stable nimodipine formulation for injection and method for preparing same
The present invention relates to the technical field of pharmaceutics, and in particular, to a safe and stable nimodipine formulation for injection and a method for preparing same. The present invention provides a lyophilized nimodipine-cyclodextrin powder for injection, comprising sulfobutylether-β-cyclodextrin, which can significantly improve the solubility, safety, and dilution stability of nimodipine, and increase patient compliance and the convenience of clinical use. Compared with a commercially available nimodipine injection NIMOTOP, the present invention has significant advantages in safety and dilution stability.
1 . A safe and stable nimodipine formulation for injection comprising sulfobutyl ether-β-cyclodextrin and nimodipine,
wherein the mass ratio of sulfobutyl ether-β-cyclodextrin to nimodipine is 350:1 to 700:1.
2 . The nimodipine for injection according to claim 1 , wherein the content of nimodipine is 0.01-0.14% g/mL, and the content of sulfobutyl ether-β-cyclodextrin is 10-50% g/mL.
3 . The safe and stable nimodipine formulation for injection according to claim 1 , wherein the mass ratio of sulfobutyl ether-β-cyclodextrin to nimodipine is 400:1 to 600:1, the content of nimodipine is 0.02-0.10% g/mL, and the content of sulfobutyl ether-β-cyclodextrin is 10-40% g/mL.
4 . The safe and stable nimodipine formulation for injection according to claim 1 , wherein the mass ratio of sulfobutyl ether-β-cyclodextrin to nimodipine is 450:1 to 550:1, the content of nimodipine is 0.04-0.06% g/mL, and the content of sulfobutyl ether-β-cyclodextrin is 20-30% g/mL.
5 . A safe and stable nimodipine formulation for injection comprising sulfobutyl ether-β-cyclodextrin and nimodipine, wherein the mass ratio of sulfobutyl ether-β-cyclodextrin to nimodipine is 350:1 to 700:1; and the nimodipine formulation for injection comprises:
Nimodipine
0.01-0.20%
g/mL
Sulfobutyl ether-β-cyclodextrin
10-50%
g/mL
Ethanol
0-5%
mL/mL
Water for injection
Balance.
6 . The safe and stable nimodipine formulation for injection according to claim 5 , wherein the nimodipine formulation for injection comprises:
Nimodipine
0.01-0.14%
g/mL
Sulfobutyl ether-β-cyclodextrin
10-50%
g/mL
Ethanol
0-3.5%
mL/mL
Water for injection
Balance.
7 . A preparation method for the safe and stable nimodipine formulation for injection as described in claim 5 , wherein the preparation method comprises the following steps:
(a) weighing the prescribed amount of sulfobutyl ether-β-cyclodextrin, adding an appropriate amount of water for injection, and stirring at a certain temperature to dissolve to obtain a sulfobutyl ether-β-cyclodextrin aqueous solution;
(b) weighing the prescribed amount of nimodipine and adding the prescribed amount of ethanol to dissolve to obtain a nimodipine ethanol solution;
(c) adding the solution of step (b) or nimodipine powder to the solution of step (a) under a certain stirring temperature and speed, stirring for a certain period, adding water for injection to the full amount, sterilely filtering with a 0.22 μm microporous filter membrane, filling, freeze-drying, and packaging to obtain the safe and stable nimodipine for injection.
8 . The preparation method according to claim 7 , wherein the stirring temperature in steps (a) and (c) is 20-100° C.
9 . The preparation method according to claim 7 , wherein the stirring time in step (c) is 10-300 minutes.
10 . The preparation method according to claim 7 , wherein the stirring speed in step (c) is 0.5-10.0 m/s.
11 . The safe and stable nimodipine formulation for injection according to claim 1 , wherein the nimodipine formulation has a dilution stability time of more than 24 h.
12 . The safe and stable nimodipine formulation for injection according to claim 5 , wherein the nimodipine formulation has a dilution stability time of more than 24 h.