Oral dosage forms of ketamine

1. An oral dosage form comprising ketamine or a pharmaceutically acceptable salt or solvate thereof,

wherein the dosage form provides an in vitro release of ketamine, when measured according to the USP Basket Method I in 0.1M HCl at 37° C. at 100 rpm, of 0 to 40% after 2 hours, of 10 to 70% after 4 hours, of 30 to 85% after 6 hours and of 45 to 100% after 8 hours,

wherein the dosage form provides an in vitro release of ketamine, when measured according to the USP 1 Basket Method in 0.1M HCl at 100 rpm, after one hour at 37° C., in an aqueous solution containing 20% by volume of ethanol, in a ratio of less than 2:1 relative to the amount of ketamine released, so measured, after one hour at 37° C. in an ethanol-free aqueous solution,

wherein the dosage form is a multi-particulate controlled release tablet,

wherein the tablet comprises pellets each containing

i) a core comprising

1 to 30 wt. % inert beads,

5 to 400 mg and 1 to 40 wt. % ketamine hydrochloride,

0.01 to 10 wt. % binder, and

0 to 10 wt. % glidant, and

ii) a release control layer comprising

1 to 40 wt. % of a release control substance coated upon the core, wherein the release control substance is a water insoluble polymer,

0.01 to 10 wt % pore builder,

0.01 to 10 wt. % plasticizer, and

0 to 15 wt. % glidant, and

wherein the pellets are contained in an external phase comprising

carboxymethyl cellulose, optionally in the form of a salt, as a pharmaceutically acceptable excipient,

20 to 85 wt. % filler,

0 to 3 wt. % lubricant, and

0 to 5 wt. % glidant,

wherein the tablet optionally comprises an external film coating, and

wherein all wt. % are based on the total weight of the tablet, without the film coating.

2. The oral dosage form according to claim 1 , wherein the core comprises a layer comprising ketamine coated on an inert core.

3. The oral dosage form according to claim 1 , wherein the release control substance is an alkyl cellulose.

4. The oral dosage form according to claim 1 , wherein the dosage form is administered once or twice daily.

5. The oral dosage form according to claim 1 , wherein the administration of a single oral dosage form leads in-vivo to a C max of ketamine of 1 to 150 ng/ml and to a AUC 0-∞ of 5 to 1000 h·ng/ml.

6. The oral dosage form according to claim 1 , wherein T max of ketamine is 3 to 9 h.

7. The oral dosage form according to claim 1 having an absolute bioavailability F abs of 5 to 25%.

8. A method for the treatment of neuropathic pain and to avoid dose dumping upon ingestion of alcohol, said method comprising orally administering the oral dosage form of claim 1 to a subject in need thereof.

9. A method for the treatment of a patient suffering from spinal cord injury, multiple sclerosis, cancer, immune mediated disorders, a metabolic condition, herpes zoster infection, HIV-related neuropathies, nutritional deficiencies and to avoid dose dumping upon ingestion of alcohol by the patient, said method comprising orally administering to the patient the oral dosage form of claim 1 .

10. A method for preparing an oral dosage form according to claim 1 , comprising:

a) coating inert cores with a layer comprising ketamine or a pharmaceutically acceptable salt or solvent thereof,

b) coating the coated inert cores with a release-control layer comprising the release-controlling substance, thus forming pellets,

c) mixing the pellets with at least one pharmaceutically acceptable excipient,

d) forming a tablet from the mixture comprising the pellets and the at least one pharmaceutically acceptable excipient.

11. The oral dosage form according to claim 1 , wherein the release control substance is ethylcellulose.

12. The oral dosage form according to claim 1 , wherein the tablet comprises a break-line for facilitating its division in to into two or more units.

13. The oral dosage form according to claim 1 , wherein ratio is less than 1.5:1.

14. The oral dosage form according to claim 1 , wherein ratio is less than 1.2:1.

15. A method of claim 9 wherein the metabolic condition is diabetes.