Embedded micellar nanoparticles

1. A solid composition comprising nanosized micelles, wherein said micelles comprise a poorly soluble active substance dissolved in an auxiliary material or a mixture of auxiliary materials,

wherein said auxiliary material or said mixture of auxiliary materials is chosen from polyoxyethylene stearates, Polyoxyethylene sorbitan fatty acid esters, Polyoxyethylene Castor Oil Derivatives, Vitamin E TPGS, nonionic polyoxyethylene-polyoxypropylene block co-polymers, water-soluble long chain organic phosphate esters, and inulin lauryl carbamate,

wherein said micelles are embedded in a water-soluble carrier, wherein said water-soluble carrier is chosen from:

alkylcelluloses;

hydroxyalkylcelluloses;

hydroxyalkyl-alkylcelluloses;

carboxyalkylcelluloses;

alkali metal salts of carboxyalkylcelluloses;

carboxyalkylalkylcelluloses;

starches;

pectines;

chitin derivates;

polysaccharides, alkali metal and ammonium salts thereof;

carrageenans, galactomannans, tragacanth, agar-agar, gummi arabicum, guar gummi, and xanthan gummi;

polyacrylic acids and the salts thereof;

polymethacrylic acids and the salts thereof, methacrylate copolymers;

polyvinylalcohol;

polvinylpyrrolidone, copolymers of polyvinylpyrrolidone with vinyl acetate;

polyalkylene oxides; and

copolymers of ethylene oxide and propylene oxide; and

wherein the composition is a powder that remains free flowing when heated above the melting point of the main auxiliary material.

2. The composition according to claim 1 , wherein said micelles have an effective average particle size of less than about 1000 nm.

3. The composition according to claim 2 , wherein said micelles have an effective average particle size of less than about 500 nm.

4. The composition according to claim 1 , wherein said micelles have an effective average particle size of less than about 1000 nm.

5. The composition according to claim 4 , wherein said micelles have an effective average particle size of less than about 500 nm.

6. The composition according to claim 1 , wherein said auxiliary material or said mixture of auxiliary materials comprises at least 10% w/w of a surfactant and optionally one or more co-solvents and/or one or more co-surfactants.

7. The composition according to claim 6 , wherein said co-solvent is chosen from alkylene glycols, polyhydric alcohols, linear polyols, and mixtures thereof.

8. The composition according to claim 7 , wherein said co-solvent is Polyethylene Glycol (PEG).

9. The composition according to claim 8 , wherein said co-solvent is Polyethylene Glycol (PEG) having a molecular weight equal to or less than 800 Daltons.

10. The composition according to claim 8 , wherein said co-solvent is Polyethylene Glycol (PEG) having a molecular weight ranging from 950 to 20,000 Daltons.

11. The composition according to claim 1 , wherein the composition is in the form of a powder, granules, a compressed tablet, a sublingual tablet, a buccal tablet, a filled capsule, or a filled sachet.

12. The composition according to claim 1 , wherein said poorly soluble active substance is chosen from cannabinoid agonists, cannabinoid inverse agonists and cannabinoid antagonists.

13. The composition according to claim 12 , wherein said poorly soluble active substance is (4S)-3-(4-chlorophenyl)-4,5-dihydro-N-methyl-4-phenyl-N′-(1-piperidinyl-sulfonyl) - 1H-pyyrazole-1-carboximidamide.

14. The composition according to claim 12 , wherein said poorly soluble active substance is (4S)-3-(4-chlorophenyl)-N-[(4-chlorophenyl)sulfonyl]-4,5-dihydro-N′-methyl-4-phenyl -1H-pyrazole-1-carboximidamide.

15. The composition according to claim 12 , wherein said poorly soluble active substance is (4S)-3-(4-chlorophenyl)-4,5-dihydro-N-methyl-4-phenyl-N′-[[4-(trifluoromethyl)-phenyl]sulfonyl]-1H-pyrazole-1-carboximidamide.

16. A process for preparing a solid pharmaceutical composition, comprising:

A) combining a poorly soluble active substance, an auxiliary material or a mixture of auxiliary materials, optionally one or more additional auxiliary materials, a matrix forming material, and water to form nanosized micelles; and

B) drying the mixture obtained in (A) to obtain a solid pharmaceutical composition, wherein the micelles are embedded in the matrix forming material, and wherein the composition is a powder that remains free flowing when heated above the melting point of the main auxiliary material;

wherein said auxiliary material or said mixture of auxiliary materials is chosen from polyoxyethylene stearates, Polyoxyethylene sorbitan fatty acid esters, Polyoxyethylene Castor Oil Derivatives, Vitamin E TPGS, nonionic polyoxyethylene-polyoxypropylene block co-polymers, water-soluble long chain organic phosphate esters, and inulin lauryl carbamate; and

wherein said water-soluble carrier is chosen from:

alkylcelluloses;

hydroxyalkylcelluloses;

hydroxyalkyl-alkylcelluloses;

carboxyalkylcelluloses;

alkali metal salts of carboxyalkylcelluloses;

carboxyalkylalkylcelluloses;

starches:

pectines;

chitin derivates;

polysaccharides, alkali metal and ammonium salts thereof;

carrageenans, galactomannans, tragacanth, agar-agar, gummi arabicum, guar gummi, and xanthan gummi;

polyacrylic acids and the salts thereof;

polymethacrylic acids and the salts thereof, methacrylate copolymers;

polyvinylalcohol;

polvinylpyrrolidone, copolymers of polyvinylpyrrolidone with vinyl acetate:

polyalkylene oxides; and

copolymers of ethylene oxide and propylene oxide.

17. The process according to claim 16 , wherein the combining of step (A) comprises:

(a) dissolving the poorly soluble active substance in the auxiliary material or the mixture of auxiliary materials;

(b) optionally adding one or more additional auxiliary materials to the solution obtained in (a);

(c) mixing the solution obtained in (a) or (b) with water to form the nanosized micelles; and

(d) dissolving the matrix forming material in the mixture obtained in (c).

18. The process according to claim 16 , wherein step the combining of step (A) comprises:

(a) dissolving the poorly soluble active substance in the auxiliary material or the mixture of auxiliary materials;

(b) optionally adding one or more additional auxiliary materials to the solution obtained in (a);

(c) dissolving the matrix forming material in water; and

(d) mixing the solution obtained in (a) or (b) with the solution obtained in (c) to form the nanosized micelles.

19. The process according to claim 16 , wherein the combining of step (A) comprises:

(a) dissolving the poorly soluble active substance in the auxiliary material or the mixture of auxiliary materials;

(b) dissolving the solution obtained in (a) in water to form the nanosized micelles;

(c) optionally adding one or more additional auxiliary materials to the solution obtained in (b); and

(d) dissolving the matrix forming material in the mixture obtained in (b) or (c).

20. The process according to claim 16 , wherein the combining of step (A) comprises:

(a) dissolving the auxiliary material or the mixture of auxiliary materials in water;

(b) dissolving the poorly soluble active substance in the solution obtained in (a);

(c) optionally adding one or more additional auxiliary materials to the solution obtained in (b), wherein the solution obtained in (b) or (c) contains micelles comprising the poorly soluble active substance; and

(d) dissolving the matrix forming material in the solution obtained in (b) or (c).

21. The process according to claim 16 , wherein said drying of (B) is performed by freeze drying, spray drying, freeze spray drying, vacuum drying, or a combination thereof.

22. The process according to claim 16 , further comprising processing said solid pharmaceutical composition into granules, a compressed tablet, a sublingual tablet, a buccal tablet, or filling a capsule or sachet with said solid pharmaceutical composition.