Preservative free insulin formulations

1. An insulin formulation specifically adapted for aerosolization, the formulation comprising:

a major amount of water;

a minor amount of insulin; and

2 to 4 Zn 2+ per insulin hexamer,

wherein the formulation is preservative free thereby facilitating aerosolization of the formulation as an aerosolized liquid spray; and wherein the liquid spray is produced-without substantial foaming of the insulin formulation.

2. The insulin formulation of claim 1 , wherein the formulation has a concentration of about 100 IU/ml to about 1200 IU/ml of human insulin.

3. The insulin formulation of claim 1 , wherein the water comprises in volume about 99.8% to about 97.0%, and the insulin comprises in volume about 0.2% to about 3.0%.

4. The insulin formulation of claim 1 , wherein the formulation does not include phenol, metacresol, chloro-cresol, or thymol.

5. The insulin formulation of claim 1 , wherein the formulation does not include non-phenol preservatives selected from the group consisting of bicyclic aliphatic alcohols, tricyclic aliphatic alcohols, bicyclic aliphatic purines, and tricyclic aliphatic purines.

6. The insulin formulation of claim 1 , wherein the formulation does not include surfactants or detergents.

7. The insulin formulation of claim 1 , wherein the formulation comprises glycol.

8. The insulin formulation of claim 1 , wherein the formulation is aerosolizable using a vibrating aperture plate without substantial foaming of the formulation.

9. The insulin formulation of claim 8 , wherein the vibrating aperture plate has a plurality of apertures and vibrates at a frequency in a range from about 50 kHz to about 150 kHz.

10. A preservative-free insulin formulation comprising:

100 IU/ml to about 1200 IU/ml of human insulin;

a minor amount of HCl and NaOH; and

2 to 4 Zn 2+ per insulin hexamer,

wherein the formulation does not comprise a preservative.

11. The preservative-free insulin formulation of claim 10 , wherein the formulation has a pH of about 7.4.

12. The preservative-free insulin formulation of claim 10 , wherein the formulation does not include phenol, metacresol, chloro-cresol, or thymol.

13. The preservative-free insulin formulation of claim 10 , wherein the formulation does not include non-phenol preservatives selected from the group consisting of bicyclic aliphatic alcohols, tricyclic aliphatic alcohols, bicyclic aliphatic purines, and tricyclic aliphatic purines.

14. The preservative-free insulin formulation of claim 10 , wherein the formulation does not include surfactants or detergents.

15. The preservative-free insulin formulation of claim 10 , wherein the formulation comprises glycol.

16. A method for manufacturing a preservative-free insulin formulation comprising:

suspending human insulin powder in water, the human insulin powder comprising 2 to 4 Zn 2+ per insulin hexamer;

adding a minor amount of HCl to dissolve the human insulin and form an insulin solution;

after the human insulin is dissolved, adding a minor amount of NaOH to titrate the insulin solution to a desired pH; and

adding additional water to adjust the concentration of the insulin solution to 100 IU/ml to 1200 IU/ml human insulin;

wherein the inulin solution is devoid of preservatives.

17. The method of claim 16 , wherein the pH is about 3.0 when the HCl is added.

18. The method of claim 16 , wherein the insulin solution is titrated to about pH 7.4.

19. The method of claim 16 , wherein the formulation does not include phenol, metacresol, chloro-cresol, or thymol.

20. The method of claim 16 , wherein the formulation does not include non-phenol preservatives selected from the group consisting of bicyclic aliphatic alcohols, tricyclic aliphatic alcohols, bicyclic aliphatic purines, and tricyclic aliphatic purines.

21. The method of claim 16 , wherein the insulin formulation is also devoid of surfactants and detergents.