Compositions and Methods For Increasing the Bioavailability of Pulmonarily Administered Insulin
A pharmaceutical composition suitable for pulmonary delivery includes insulin and EDTA. The presence of EDTA is effective to increase the relative pulmonary bioavailability of the insulin compared to the relative pulmonary bioavailability exhibited by a composition having the same components but absent the EDTA. The composition is in dry powder form. A method of treating or ameliorating diabetes or a related condition in a mammal includes administering by inhalation a pharmacologically effective amount of the composition. A method of improving the pulmonary bioavailability of an insulin composition includes adding EDTA to an insulin composition suitable for pulmonary delivery, wherein the composition is in dry powder form.
1 . A pharmaceutical composition suitable for pulmonary delivery, comprising:
insulin; and
EDTA;
wherein the presence of said EDTA is effective to increase the relative pulmonary bioavailability of the insulin compared to the relative pulmonary bioavailability exhibited by a composition having the same components but absent said EDTA, and
wherein the composition is in dry powder form.
2 . The pharmaceutical composition of claim 1 , wherein the EDTA is a sodium salt of ethylene diaminetetraacetic acid.
3 . The pharmaceutical composition of claim 1 , comprising from about 5 to about 90 solid weight percent of said EDTA.
4 . The pharmaceutical composition of claim 1 , comprising from about 10 to about 85 solid weight percent of said EDTA.
5 . The pharmaceutical composition of claim 1 , comprising from about 30 to about 70 solid weight percent of said EDTA.
6 . The pharmaceutical composition of claim 1 , comprising from about 50 to about 70 solid weight percent of said EDTA.
7 . The pharmaceutical composition of claim 1 , wherein particles of the powder have a mass median diameter (MMD) from about 1-5 microns.
8 . The pharmaceutical composition of claim 1 , wherein particles of the powder have a mass median aerodynamic diameter (MMAD) of less than about 10 microns.
9 . The pharmaceutical composition of claim 1 , wherein particles of the powder have an MMAD of less than about 5 microns.
10 . The pharmaceutical composition of claim 1 , wherein particles of the powder have an MMAD of less than about 3.5 microns.
11 . The pharmaceutical composition of claim 1 , which, when administered by inhalation, results in a relative pulmonary bioavailability that is at least about 3 fold of the relative pulmonary bioavailability of a composition having the same components and absent said EDTA.
12 . The pharmaceutical composition of claim 1 , which, when administered by inhalation, results in a relative pulmonary bioavailability that is at least about 2 fold of the relative pulmonary bioavailability of a composition having the same components and absent said EDTA.
13 . The pharmaceutical composition of claim 1 , which, when administered by inhalation, results in a relative pulmonary bioavailability that is at least about 1.5 fold of the relative pulmonary bioavailability of a composition having the same components and absent said EDTA.
14 . The pharmaceutical composition of claim 1 , which, when administered by inhalation, results in a relative pulmonary bioavailability that is at least about 1.2 fold of the relative pulmonary bioavailability of a composition having the same components and absent said EDTA.
15 . A method of treating or ameliorating diabetes or a related condition in a mammal, which method comprises administering by inhalation a pharmacologically effective amount of the composition of claim 1 .
16 . The method of claim 15 , wherein the EDTA is a sodium salt of EDTA.
17 . The method of claim 15 , wherein the composition comprises from about 5 to about 90 solid weight percent of said EDTA.
18 . The method of claim 15 , wherein the composition comprises from about 10 to about 85 solid weight percent of said EDTA.
19 . The method of claim 15 , wherein the composition comprises from about 30 to about 75 solid weight percent of said EDTA.
20 . The method of claim 15 , wherein the composition comprises from about 50 to about 70 solid weight percent of said EDTA.
21 . The method of claim 15 , wherein particles of the powder have an MMD from about 1-5 microns.
22 . The method of claim 15 , wherein particles of the powder have an MMAD of less than about 10 microns.
23 . The method of claim 15 , wherein particles of the powder have an MMAD of less than about 5 microns.
24 . The method of claim 15 , wherein particles of the powder have an MMAD of less than about 3.5 microns.
25 . The method of claim 15 , wherein the inhalation results in a relative pulmonary bioavailability that is at least about 3 fold of the relative pulmonary bioavailability of a composition having the same components and absent said EDTA.
26 . The method of claim 15 , wherein the inhalation results in a relative pulmonary bioavailability that is at least about 2 fold of the relative pulmonary bioavailability of a composition having the same components and absent said EDTA.
27 . The method of claim 15 , wherein the inhalation results in a relative pulmonary bioavailability that is at least about 1.5 fold of the relative pulmonary bioavailability of a composition having the same components and absent said EDTA.
28 . The method of claim 15 , wherein the inhalation results in a relative pulmonary bioavailability that is at least about 1.2 fold of the relative pulmonary bioavailability of a composition having the same components and absent said EDTA.
29 . The method of claim 15 , wherein the composition is administered using a dry powder inhaler.
30 . The method of claim 15 , wherein the composition is administered using an MDI.
31 . The method of claim 15 , wherein said pharmacologically effective amount is administered in a plurality of unit dosages.
32 . A method of improving the pulmonary bioavailability of an insulin composition, comprising adding EDTA to an insulin composition suitable for pulmonary delivery, wherein the composition is in dry powder form.
33 . The method of claim 32 , wherein the EDTA is a sodium salt of EDTA.
34 . The method of claim 32 , wherein the composition comprises from about 5 to about 90 solid weight percent of said EDTA.
35 . The method of claim 32 , wherein the composition comprises from about 10 to about 85 solid weight percent of said EDTA.
36 . The method of claim 32 , wherein the composition comprises from about 30 to about 75 solid weight percent of said EDTA.
37 . The method of claim 32 , wherein the composition comprises from about 50 to about 70 solid weight percent of said EDTA.
38 . The method of claim 32 , wherein particles of the powder have an MMD from about 1-5 microns.
39 . The method of claim 32 , wherein particles of the powder have an MMAD of less than about 10 microns.
40 . The method of claim 32 , wherein particles of the powder have an MMAD of less than about 5 microns.
41 . The method of claim 32 , wherein particles of the powder have an MMAD of less than about 3.5 microns.
42 . The method of claim 32 , wherein the improvement results in a relative pulmonary bioavailability that is at least about 3 fold of the relative pulmonary bioavailability of a composition having the same components and absent said EDTA.
43 . The method of claim 32 , wherein the improvement results in a relative pulmonary bioavailability that is at least about 2 fold of the relative pulmonary bioavailability of a composition having the same components and absent said EDTA.
44 . The method of claim 32 , wherein the improvement results in a relative pulmonary bioavailability that is at least about 1.5 fold of the relative pulmonary bioavailability of a composition having the same components and absent said EDTA.
45 . The method of claim 32 , wherein the improvement results in a relative pulmonary bioavailability that is at least about 1.2 fold of the relative pulmonary bioavailability of a composition having the same components and absent said EDTA.
46 . The method of claim 32 , wherein the composition is administered using a dry powder inhaler.
47 . The method of claim 32 , wherein the composition is administered using an MDI.
48 . The method of claim 32 , wherein said pharmacologically effective amount is administered in a plurality of unit dosages.