Galenical system for active transport, method for preparation and use

• US 8,911,788 B2
• Filed: 04/26/2010
• Issued: 12/16/2014
• Est. Priority Date: 03/24/2003
• Status: Active Grant

• Current Assignee: Capsugel France SAS (Lonza Group AG)
• Original Assignee: Capsugel France SAS (Lonza Group AG)
• Inventors: Ioualalen, Karim, Raynal, Rose-Anne
• Primary Examiner(s): Palenik, Jeffrey T
• Application Number:
  US12/767,248
• Publication Number:
  US 20100221298A1
• Time in Patent Office: 1,695 Days
• Field of Search: None
• US Class Current: 424/502
• CPC Class Codes: A61K 31/167 having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
• CPC Class Codes: A61K 31/65 Tetracyclines
• CPC Class Codes: A61K 31/7048 having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin , digitoxin or digoxin
• CPC Class Codes: A61K 47/12 Carboxylic acids; Salts or anhydrides thereof
• CPC Class Codes: A61K 47/44 Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin synthetic glycerides, e.g. medium-chain triglycerides, A61K47/14
• CPC Class Codes: A61K 9/0095 Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches A61K9/0007 takes precedence; eatable gels or foams A61K9/0056; oral mucosa adhesive forms A61K9/006
• CPC Class Codes: A61K 9/14 Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles microspheres A61K9/16; microcapsules A61K9/50; nanocapsules, nanoparticles of the matrix type A61K9/51
• CPC Class Codes: A61K 9/1617 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 23/02 Local anaesthetics
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system

Abstract

The invention relates to a novel galenical system for taste masking, protecting an active substance, in particular in an acid medium, modulating releasing properties, masking mucous irritability and toxicity of certain active substances, for preparing aqueous forms which have a masked taste, are stable and pH independent. Said invention also relates, in particular to a galenical system which is embodied in the form of lipidic solid particles and strictly hydrophobic and devoid of water, surface active agents, emulsifiers, solvent traces and which is characterized in that it comprises at least one type of hydrophobic wax and at least one type of fatty non-neutralized acid.

Claims

1. A galenic system in the form of strictly hydrophobic solid lipidic particles comprising at least one hydrophobic wax;

at least one non-neutralized fatty acid; and

an active constituent that has been eliminated from the surface of the lipidic particles by washing said particles with a washing mixture comprising ethanol, wherein the particles have a size between 0.5 microns and 1,500 microns, contain no water, surfactants, emulsifying agents, or traces of solvents, and have a melting temperature between 15°

C. and 75°

C.

2. A galenic system according to claim 1, wherein said galenic system is solid at a temperature of up to 45°

C.

3. A galenic system according to claim 1, wherein the lipidic particles are in a spherical form.

4. A galenic system according to claim 1, wherein the hydrophobic wax is a vegetable, animal or mineral wax, or a mix of at least one wax and at least one non-amphiphilic oil.

5. A galenic system according to claim 1, wherein the quantity of wax is between 0.5% and 99%.

6. A galenic system according to claim 1, wherein the melting point of the wax is between 15°

C. and 75°

C.

7. A galenic system according to claim 1, wherein the wax is chosen from among triglycerides and derivatives, palm oil, Carnauba wax, Candellila wax, Alfa wax, cocoa butter, ozokerite, vegetable waxes, beeswaxes and modified beeswaxes.

8. A galenic system according to claim 1, wherein the non-neutralized fatty acid is chosen from among fatty acids with linear chains with between 4 and 18 carbon atoms.

9. A galenic system according to claim 1, wherein the fatty acid has a content by mass of between 0.5% and 75%.

10. A galenic system according to claim 1, wherein said galenic system in the form of lipidic particles with a size of between 10 microns and 250 microns.

11. A galenic system according to claim 1, having a melting temperature between 30°

C. and 45°

C., after incorporation of the active constituent.

12. A galenic system according to claim 1, wherein the capacity of the particles for holding the active constituent varies from 0.02% to 75% by weight of the particles.

13. A galenic system according to claim 1, wherein the capacity of the particles for holding the active constituent varies from 5 to 50%.

14. A galenic system according to claim 1, wherein said galenic system solid at a temperature of up to 37.5°

C.

15. A galenic system according to claim 1, wherein the quantity of wax is between 1% and 55%.

16. A galenic system according to claim 1, wherein the melting point of the wax is between 30°

C. and 45°

C.

17. A galenic system according to claim 1, wherein the wax is olive wax, rice wax, hydrogenated jojoba wax or absolute flower waxes.

18. A galenic system according to claim 1, wherein the non-neutralised fatty acid is myristic acid, lauric acid, palmitic acid or oleic acid.

19. A galenic system according to claim 1, wherein the fatty acid has a content by mass of between 1% and 30%.

20. A galenic system according to claim 1, further comprising a mineral filler.

21. A galenic system according to claim 1, wherein the active ingredient is selected from the group consisting of hydrophilic compounds and hydrophobic compounds.

22. A galenic system according to claim 1, wherein the active ingredient is selected from the group consisting of antibiotics, antifungicides, antiparasites, anti-malaria agents, adsorbents, hormones and derivatives, nicotine, antihistamines, steroidal and non-steroidal anti-inflammatory agents, antiallergic agents, antalgics, local anaesthetics, antivirals, antibodies and molecules acting on the immunitary system, cytostatics and anticancer agents, antalgics, hypolipemiants, vasodilators, vasoconstrictors, inhibitors of the angiotensin and phosphodiesterase conversion enzyme, nitrated and antianginal derivatives, betablocking agents, calcium inhibitors, antidiuretics and diuretics, bronchodilators, opiates and derivatives, barbiturates, benzodiazepines, molecules acting on the central nervous system, nucleic acids, peptides, anthracenic compounds, paraffin oil, polyethylene glycol, mineral salts, antispasmodic agents, gastric antisecretion agents, clay and polyvinylpyrrolidone gastric cytoprotectors, starch, and mixtures thereof.

23. A galenic system according to claim 1, wherein the at least one hydrophobic wax is present in an amount ranging from 1% to 50%.

24. A galenic system according to claim 1, wherein the at least one hydrophobic wax is present in an amount of about 80%.

25. A galenic system according to claim 1, wherein the at least one hydrophobic wax is present in an amount of about 70%.

26. A galenic system according to claim 1, wherein the at least one hydrophobic wax is present in an amount of about 50%.

27. A galenic system according to claim 26, wherein the at least one hydrophobic wax is beeswax.

28. A process for preparing the galenic system according to claim 1, comprising:

a.) hot mixing the wax and the non-neutralized fatty acid, while stirring, at 2°

C. or 3°

C. above the melting point of the compound with the highest melting point;

b.) forming lipidic droplets comprising the active constituent by dispersing the wax/fatty acid mixture obtained in the first step in a gel, wherein said gel;

i.) is immiscible with said mixture;

ii.) has been adjusted to be the same temperature as the wax/fatty acid mixture with which it is mixed; and

iii.) contains a gelling agent at a concentration between 0.1 g/L to 30 g/L;

c.) immediately at the end of injection, cooling the droplets below the solidification temperature of the mix and washing the formed particles with a washing mixture comprising ethanol; and

d.) recovering the washed particles by sieving and drying.

29. A composition comprising at least one galenic system containing an active constituent as described in claim 1.

30. A composition according to claim 29, contained in a cosmetic, pharmaceutical, veterinary or food composition.

31. A composition according to claim 29, to be used for oral administration or by injection.

32. A process according to claim 28, wherein the gelling agent is present at a concentration between 0.2 g/L and 20 g/L.

33. A process according to claim 28, wherein the washing mixture contains between 0% and 25% ethanol.

34. A process according to claim 28, wherein the gel is prepared with a shear thinning and non-surface active gelifying agent chosen among carboxyvinyl polymers such as polyacrylic polymers not modified by hydrophobic groups or surfactants, carrageenans, thickeners and polysaccharidic gels such as xanthenes, guar and carob gums, alginates, cellulose derivatives, pectins, agar or a mix of these products.