Pharmaceutical formulations

• US 7,025,992 B2
• Filed: 09/12/2001
• Issued: 04/11/2006
• Est. Priority Date: 02/14/2001
• Status: Active Grant

• Current Assignee: GW Research Limited (Jazz Pharmaceuticals Plc)
• Original Assignee: GW Pharmaceuticals Limited (Jazz Pharmaceuticals Plc)
• Inventors: Whittle, Brian A., Guy, Geoffrey W.
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): YOUNG, MICAH PAUL
• Application Number:
  US09/951,022
• Publication Number:
  US 20030021752A1
• Time in Patent Office: 1,672 Days
• Field of Search: 449/448, 449/449, 449/450, 449/260, 514/937
• US Class Current: 424/725
• CPC Class Codes: A61K 9/0031 Rectum, anus
• CPC Class Codes: A61K 9/0056 Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
• CPC Class Codes: A61K 9/006 Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
• CPC Class Codes: A61K 9/1075 Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers A61K9/0026 takes precedence
• CPC Class Codes: A61K 9/122 Foams; Dry foams edible foams A61K9/0056
• CPC Class Codes: A61K 9/209 containing drug in at least two layers or in the core and in at least one outer layer

Abstract

The invention relates to pharmaceutical formulations for use in the administration of lipophilic medicaments via mucosal surfaces. In particular the invention provides pharmaceutical formulations for use in administration of a lipophilic medicament via a mucosal surface which upon hydration form an emulsion containing the lipophilic medicament which is capable of adhering to a mucosal surface and allowing controlled release of the medicament. The invention further provides pharmaceutical formulations which contain, as active ingredients, specific combinations of cannabinoids in pre-defined ratios.

Claims

1. A Cannabis-based pharmaceutical formulation “

for use in administration via a mucosal surface”

which comprises both the cannabinoids cannabidiol (CBD) and tetrahydrocannabinol (THC), or the cannabinoids tetrahydrocannabinovarin (THCV) and cannabidivarin (CBDV), wherein the formulation is in a liquid dosage form producing particles having a mean aerodynamic particle size between 15 and 45 microns.

2. A pharmaceutical formulation according to claim 1 wherein the particle size is between 20 and 40 microns.

3. A pharmaceutical formulation according to claim 1 wherein to average particle size is about 33 microns.

4. A pharmaceutical formulation according to claim 1 which comprises both the cannabinoids cannabidiol (CBD) and tetrahydrocannabinol (THC) in approximately equal amounts by weight.

5. A pharmaceutical formulation according to claim 1 which comprises both the cannabinoids cannabidiol (CBD) and tetrahydrocannabinol (THC), wherein the THC is present in an amount by weight which is greater than the amount by weight of CBD.

6. A pharmaceutical formulation according to claim 1 which comprises both the cannabinoids cannabidiol (CBD) and tetrahydrocannabinol (THC), wherein the CBD is present in an amount by weight which is greater than the amount by weight of THC.

7. A formulation according claim 1 which is substantially free of cannabinoids other than CUD and THC.

8. A formulation according to claim 1 which is substantially free of other cannabinoids found in Cannabis sp.

9. A formulation according to claim 1 wherein said CBD and THC are in substantially pure form.

10. A formulation according to claim 1 which tither comprises one or more other cannabinoids.

11. A formulation according to claim 10 wherein the one or more other cannabinoids are tetrahydrocannabinovarin (THCV) and/or cannabidivarin (CBDV).

12. A formulation according to claim 1 wherein the CBC and THC are derived from at least one extract from at least one Cannabis plant, said at least one extract comprising all the naturally occurring cannabinoids in said plant.

13. A formulation according to claim 12 wherein the Cannabis plant is selected from Cannabis saliva, Cannabis indica, a genetic cross between them, a self-cross or a hybrid thereof.

14. A formulation according to claim 13 wherein the Cannabis plant is Cannabis saliva, subspecies indica and is selected from var. indica and var. kafiristanica.

15. A formulation as claimed in claim 12 which comprises extracts from two or more different Cannabis varieties.

16. A formulation according to claim 12 wherein said extract is prepared by supercritical or sub-critical fluid extraction of dried Cannabis plant.

22. A formulation according to claim 1 which allows delivery of at least 1.0 mg of cannabinoids per 0.1 ml of liquid formulation.

23. A formulation according to claim 12 which is a botanical drug product prepared from a botanical drug substance.

24. A formulation according to claim 12 wherein each extract is derived from a specific chemovar.

25. A formulation according to claim 23 wherein the botanical drug substance has an HPLC profile with THC, CBD and CEN having retention times of 9.6-10.6 minutes, 5.4-5.9 minutes and 7.9-8.7 minutes respectively.

26. A formulation according to claim 25 wherein the extract comprises a CBD herbal drug extract having about 84% CBD and about 6% THC.

27. A formulation according to claim 25 wherein the extract comprises a THC herbal drug extract having about 89% TEC and about 2% CBD.

28. A pharmaceutical formulation according to claim 1 which comprises both the cannabinoids tetrahydrocannabinovarin (THCV) and cannabidivarin (CBDV) wherein the CBDV is present in an amount by weight which is greater than the amount by weight of THCV.

29. A formulation according to claim 28 which further comprises CBD and/or THC.

30. A formulation according to claim 28 which is substantially free from other cannabinoids found in Cannabis sp.

31. A formulation according to claim 28 wherein the CBDV and THCV form part of an extract from a Cannabis plant, said extract comprising all of the naturally occurring cannabinoids in said plant.

32. A formulation according to claim 31 wherein the Cannabis plant is selected from Cannabis sativa, Cannabis indica or a genetic cross between them, a self-cross or a hybrid thereof.

33. A formulation according to claim 28 which allows delivery of at least 1.0 mg of cannabinoids per 0.1 ml of liquid formulation.

34. A formulation according to claim 28 which is a botanical drug product prepared from a botanical drug substance.

35. A formulation according to claim 28 wherein each extract is derived from a specific chemovar.

37. A formulation according to claim 1 which is not in the form of a propellant-driven aerosol or a propellant-driven liquid spray.

38. A formulation according to claim 1 which is in the form of a pump action spray.

17. A method of preparing a Cannabis-based pharmaceutical formulation which comprises CBD and THC or CBDV and THCV which method comprises the steps of:

a) providing at least one dried Cannabis plant containing CBD and THC or CBDV and THCV;

b) preparing an extract of said at least one Cannabis plant;

c) formulating a material from said extract or extracts prepared in step (b)

d) further formulating the product of step (c) into a pharmaceutical formulation in a liquid dosage form producing particles having a mean aerodynamic particle size between 15 and 45 microns.

18. A method according to claim 17 wherein the extract of step (b) is prepared using at least one of the following procedures:

(i) maceration, (ii) percolation, (iii) extraction with solvent such as C₁-C₅ alcohols, norflurane or HFA227, and (iv) subcritical or supercritical fluid extraction.

19. A method according to claim 17 wherein prior to extraction said dried Cannabis is heated to a temperature of from about 60°

C. to about 225°

C., preferably about 100°

C. to about 15°

C., to decarboxylate the acid form of any cannabinoids present in the extract.

20. A method according to claim 17 which comprises extracting said at least one Cannabis plant with supercritical or subcritical CO_2.

21. A method according to any one of claim 20 wherein after extraction with said supercritical or subcritical fluid said extract is subjected to “

winterisation”

to remove waxes from the extract.

36. A Cannabis-based pharmaceutical formulation which is obtainable byte method of claim 17.