INSULIN FORMULATIONS FOR RECONSTITUTION INTO HIGH CONCENTRATION LIQUID SOLUTIONS
A dry powder insulin formulation for reconstitution including insulin, a buffering agent, and a salt. The dry powder insulin formulation includes between about 70 and 95% w/w of insulin, between about 5 and 30% w/w of the buffering agent, and less than about 1% w/w of the salt. The dry powder insulin formulation has less than about 5% water content.
1 . A dry powder insulin formulation for reconstitution comprising:
insulin;
a buffering agent; and
a salt, wherein:
the dry powder insulin formulation comprises between about 70 and 95% w/w of insulin, between about 5 and 30% w/w of the buffering agent, and less than about 1% w/w of the salt; and
the dry powder insulin formulation has less than about 5% water content.
2 . The dry powder insulin formulation for reconstitution of claim 1 , wherein:
the buffering agent comprises one or more of citrate, phosphate, acetate, Tris(hydroxymethyl)aminomethane (TRIS), glycine, or glycylglycine.
3 . The dry powder insulin formulation for reconstitution of claim 1 , wherein:
a feedstock used to produce the dry power insulin formulation has a pH of between about 7.5 and 9.0 and comprises less than about 0.6% w/w zinc.
4 . The dry powder insulin formulation for reconstitution of claim 1 , wherein:
the dry powder insulin formulation is spray-dried.
5 . The dry powder insulin formulation for reconstitution of claim 1 , wherein:
the dry powder insulin formulation is lyophilized.
6 . The dry powder insulin formulation for reconstitution of claim 1 , wherein:
the dry powder insulin formulation does not contain a stabilizer or a preservative.
7 . A method of reconstituting a dry powder insulin formulation, the method comprising:
providing a dry powder insulin formulation comprising:
insulin;
a buffering agent; and
a salt, wherein the dry powder insulin formulation has less than about 5% water content; and
combining the dry powder insulin formulation with a solvent to reconstitute the dry powder insulin formulation into a liquid insulin formulation having an insulin concentration between about 30 IU (1 mg/mL) and 2000 IU (70 mg/mL).
8 . The method of reconstituting a dry powder insulin formulation of claim 7 , wherein:
the liquid insulin formulation has a concentration of greater than about 35 mg/mL.
9 . The method of reconstituting a dry powder insulin formulation of claim 7 , wherein:
the solvent is water.
10 . The method of reconstituting a dry powder insulin formulation of claim 7 , wherein:
combining the dry powder insulin formulation with the solvent reconstitutes the dry powder insulin formulation in between about 60 and 120 seconds.
11 . The method of reconstituting a dry powder insulin formulation of claim 7 , wherein:
the dry powder insulin formulation does not contain a stabilizer or a preservative.
12 . A method of reconstituting a dry powder insulin formulation, the method comprising:
providing a dry powder insulin formulation in a first chamber of a syringe, the dry powder insulin formulation comprising:
insulin;
a buffering agent; and
a salt, wherein the dry powder insulin formulation has less than about 5% water content;
providing a solvent in a second chamber of the syringe;
introducing the solvent into the first chamber to combine the dry powder insulin formulation with the solvent to reconstitute the dry powder insulin formulation into a liquid insulin formulation;
separating the second chamber from the first chamber; and
transferring the liquid insulin formulation into an insulin delivery device.
13 . The method of reconstituting a dry powder insulin formulation of claim 12 , wherein:
the delivery device comprises a pen injector, an inhaler, or a liquid nebulizer.
14 . The method of reconstituting a dry powder insulin formulation of claim 12 , wherein:
the dry powder insulin formulation does not contain a stabilizer or a preservative.
15 . The method of reconstituting a dry powder insulin formulation of claim 12 , wherein:
transferring the liquid insulin formulation to the insulin delivery device comprises inserting the first chamber into an insulin delivery device.
16 . A method of manufacturing a dry powder insulin formulation for later reconstitution, comprising:
dissolving insulin into a feedstock having a pH of between about 7.5 to 9.0 to form an insulin-containing solution, the feedstock comprising a solvent, a buffering agent and a salt; and
drying the insulin-containing solution to form a dry powder insulin formulation comprising between about 70 and 95% w/w of insulin, between about 5 and 30% w/w of the buffering agent, less than about 1% w/w of the salt, and less than about 5% water content.
17 . The method of manufacturing a dry powder insulin formulation for later reconstitution of claim 16 , wherein:
drying the insulin-containing solution comprises spray drying the insulin-containing solution.
18 . The method of manufacturing a dry powder insulin formulation for later reconstitution of claim 17 , wherein:
an inlet temperature of gas used to spray dry the insulin-containing solution is between about 110° C. and 160° C.; and
an outlet temperature of gas used to spray dry the insulin-containing solution is between about 60° C. and 95° C.
19 . The method of manufacturing a dry powder insulin formulation for later reconstitution of claim 16 , wherein:
drying the insulin-containing solution comprises lyophilizing the insulin-containing solution.
20 . The method of manufacturing a dry powder insulin formulation for later reconstitution of claim 16 , wherein:
dry particles of the dry powder insulin formulation have a mass median diameter (MMD) of less than about 2 to 50 μm.