ORAL PHARMACEUTICAL FORMULATION COMPRISING CANNABINOIDS AND POLOXAMER
The present invention relates to a novel cannabinoid oral pharmaceutical dosage form, based on a Type IV or Type IV-like formulation, as classified using the Lipid Formulation Classification System. The formulation comprises a combination of at least two cannabinoids. The first cannabinoid is selected from the group consisting of tetrahydrocannabinol (THC) and analogues thereof; and the second cannabinoid is selected from the group consisting of cannabidiol (CBD) and analogues thereof.
1 . An oral pharmaceutical formulation comprising a first cannabinoid selected from the group consisting of tetrahydrocannabinol (THC) and analogues thereof; a second cannabinoid selected from the group consisting of cannabidiol (CBD) and analogues thereof; at least one poloxamer; and a solvent, wherein the solvent is defined according to formula (I)
wherein R 1 and R 2 are independently selected from hydrogen, C(O)CH 3 , OH, C(O)CH 3 , CH 2 OH and C(O)OCH 2 CH 3 ; R 3 is independently selected from CH 3 , CH 2 OH, OH, CH 2 OC(O)CH 3 and CH 2 C(O)CH 2 CH 3 ; and R 4 is independently selected from hydrogen and C(O)OCH 2 CH 3 .
2 . The formulation according to claim 1 , wherein the first cannabinoid is selected from the group consisting of tetrahydrocannabinol (THC), tetrahydrocannabinolic acid (THCA), tetrahydrocannabivarin (THCV) and tetrahydrocannabivarinic acid (THCVA); and the second cannabinoid is selected from the group consisting of cannabidiol (CBD), cannabidiolic acid (CBDA), cannabidivarin (CBDV) and cannabidivarinic acid (CBDVA).
3 . The formulation according to claim 1 , wherein the first cannabinoid is tetrahydrocannabinol (THC) and the second cannabinoid is cannabidiol (CBD).
4 . The formulation according to claim 1 , wherein the cannabinoids are synthetic or highly purified from their natural source.
5 . The formulation according to claim 1 , wherein the ratio by weight of the first cannabinoid to the second cannabinoid is in the range of from 100:1 to 1:100, preferably 60:1 to 1:60, more preferably 20:1 to 1:20, most preferably 5:1 to 1:5.
6 . The formulation according to claim 1 , wherein the ratio by weight of the first cannabinoid to the second cannabinoid is 1:1.
7 . The formulation according to claim 1 , wherein the total amount of cannabinoids is in an amount of from about 10 to 50 wt %, based on the total composition, preferably from about 10 to 30 wt %, more preferably from about 20 to 30 wt %.
8 . The formulation according to claim 1 , wherein the at least one poloxamer is defined according to formula (II)
wherein each a is independently an integer of from 10 to 110 and b is an integer of from 20 to 60.
9 . The formulation according to claim 8 , wherein each a is 12 and b is 20.
10 . The formulation according to claim 8 , wherein each a is 80 and b is 27.
11 . The formulation according to claim 1 , wherein the poloxamer is poloxamer 124 or poloxamer 188, or a mixture thereof.
12 . The formulation according to claim 1 , wherein the total amount of poloxamer is present in an amount of from about 25 to 75 wt %, based on the total composition, preferably from about 25 to 60 wt %, more preferably from about 30 to 60 wt %.
13 . The formulation according to claim 1 , wherein the formulation comprises two poloxamers.
14 . The formulation according to claim 13 , wherein the two poloxamers are poloxamer 124 and poloxamer 188.
15 . The formulation according to claim 1 , wherein the solvent is selected from the group consisting of diacetin, propylene glycol, triacetin, monoacetin, propylene glycol diacetate, triethyl citrate and mixtures thereof.
16 . The formulation according to claim 1 , wherein the solvent is selected from the group consisting of propylene glycol, propylene glycol diacetate, triethyl citrate and mixtures thereof.
17 . The formulation according to claim 1 , wherein the solvent is selected from the group consisting of propylene glycol, triethyl citrate and mixtures thereof.
18 . The formulation according to claim 1 , wherein the solvent is triethyl citrate.
19 . The formulation according to claim 1 , wherein the solvent is present in an amount of from about 10 to 80 wt %, based on the total composition, preferably about 20 to 80 wt %, more preferably about 20 to 65 wt %, even more preferably about 20 to 50 wt %, most preferably about 20 to 30 wt %.
20 . The formulation according to claim 1 , further comprising an antioxidant, preferably in an amount of from 0.001 to 5 wt %, more preferably 0.001 to 2.5 wt %, based on the total composition.
21 . The formulation according to claim 20 , wherein the antioxidant is selected from the group consisting of butylated hydroxyltoluene, butylated hydroxyl anisole, alpha-tocopherol (Vitamin E), ascorbyl palmitate, ascorbic acid, sodium ascorbate, ethylenediamino tetraacetic acid, cysteine hydrochloride, citric acid, sodium citrate, sodium bisulfate, sodium metabisulfite, lecithin, propyl gallate, sodium sulfate, monothioglycerol and mixtures thereof.
22 . The formulation according to claim 21 , wherein the antioxidant is selected from the group consisting of alpha-tocopherol (Vitamin E), monothioglycerol, ascorbic acid, citric acid and mixtures thereof.
23 . The formulation according to claim 1 , wherein the formulation is a Type IV or Type IV-like formulation according to the Lipid Formulation Classification System.
24 . The formulation according to claim 1 , wherein the formulation is substantially oil-free.
25 . The formulation according to claim 1 , wherein the formulation is a solid at 20° C. and 1 atm.
26 . The formulation according to claim 1 , wherein the formulation is an oral dosage form selected from the group consisting of mucoadhesive gel, a tablet, a powder, a liquid gel capsule, solid capsule, an oral solution, granule, or extrudates.
27 - 30 . (canceled)
31 . A method of treating a patient having a disease or disorder selected from the group consisting of Dravet Syndrome, Lennox Gastaut Syndrome, myocolonic seizures, juvenile myocolonic epilepsy, refractory epilepsy, schizophrenia, juvenile spasms, West syndrome, infantile spasms, refractory infantile spasms, tuberous sclerosis complex, brain tumors, neuropathic pain, cannabis use disorder, post-traumatic stress disorder, anxiety, early psychosis, Alzheimer's Disease, and autism, comprising administering a formulation according to claim 1 to the patient.
32 . A method of treating a patient having atonic, absence or partial seizures, in particular, simple or complex seizures, comprising administering a formulation according to claim 1 to the patient.
33 - 34 . (canceled)