Pharmacologically optimized multimodal drug delivery system for nordihydroguiaretic acid (NDGA)

1. A method for treating a metabolic disorder in a subject comprising oral administration of a nordihydroguiaretic acid (NDGA) composition to the subject, wherein the NDGA composition is comprised in a multi-modal drug delivery system defined by multi-modal NDGA delivery kinetics, and wherein the multi-modal drug delivery system comprises:

a first portion of the NDGA composition that is releasable at a peak pH of 1 to 4, and a second portion of the NDGA composition that is a releasable at a peak pH of 5.0 to 7.5, wherein over 30% of a total portion of NDGA present in the NDGA composition is present in the second portion, and over 90% of the total portion of NDGA present in the NDGA composition is releasable at a pH of 7.5 or lower, and

wherein the structure of the NDGA comprised in the first portion or the second portion of the single dose of NDGA is given by Formula I:

2. A method for treating a metabolic disorder in a subject comprising oral administration of a nordihydroguiaretic acid (NDGA) composition to the subject, wherein the NDGA composition is comprised in a multi-modal drug delivery system defined by multi-modal NDGA delivery kinetics, and wherein the multi-modal drug delivery system comprises:

a first portion of the NDGA composition that is releasable at a peak pH of 1 to 4, and a second portion of the NDGA composition that is releasable at a peak pH of 5.0 to 7.5, wherein over 10% of a total portion of NDGA present in the NDGA composition is present in the first portion, over 30 % of the total portion of NDGA present in the NDGA composition is present in the second portion, and over 90% of the total portion of NDGA present in the NDGA composition is releasable at a pH of 7.5 or lower, and

wherein the structure of the NDGA comprised in the first portion or the second portion of the single dose of NDGA is given by Formula I:

3. The method according to claim 1 , wherein over 10% but less than 30% of the total portion of NDGA present in the NDGA composition is present in the first portion.

4. The method according to claim 2 , wherein the multi-modal NDGA delivery kinetics comprises a bimodal absorption kinetic profile.

5. The method according to claim 1 , wherein the metabolic disorder is manifested by high free fatty acids, hyperlipidemia, hyperglycemia or hyperinsulinemia.

6. The method according to claim 5 , wherein the metabolic disorder is diabetes.

7. The method according to claim 6 , wherein the diabetes is non-insulin dependent diabetes mellitus (NIDDM).

8. The method according to claim 1 , wherein the multi-modal drug delivery system comprises a multi-layer tablet to control the release of the first portion and the second portion.

9. The method according to claim 1 , wherein the multi-modal drug delivery system comprises mixed beads or particles to control the release of the first portion and the second portion.

10. The method according to claim 1 , wherein the multi-modal drug delivery system comprises polymers to control the release of the first portion and the second portion.

11. The method according to claim 10 , wherein the polymers comprise a variably degradable polymer matrices.

12. The method according to claim 1 , wherein the multi-modal drug delivery system comprises a drug modification or conjugation.

13. The method according to claim 1 , wherein the multi-modal NDGA delivery kinetics comprise a bimodal absorption kinetic profile.

14. The method according to claim 1 , further comprising administering the NDGA composition once a day.

15. The method according to claim 1 , further comprising administering the NDGA composition twice a day.

16. The method according to claim 1 , wherein the NDGA composition contains between 200 to 2000 milligrams of NDGA.