Impregnated powder improving bioavailability and/or solubility and method of production

• US 7,569,274 B2
• Filed: 03/05/2004
• Issued: 08/04/2009
• Est. Priority Date: 03/06/2003
• Status: Expired due to Fees

• Current Assignee: SAS Galenix Innovations
• Original Assignee: SAS Galenix Innovations
• Inventors: Besse, Laurence, Alphonse, Myriam, Besse, Jerome
• Primary Examiner(s): Kiliman; Leszek
• Application Number:
  US10/547,797
• Publication Number:
  US 20060182691A1
• Time in Patent Office: 1,978 Days
• Field of Search: 428/403, 428/404, 428/405, 428/406, 428/407, 427/212, 427/213.3
• US Class Current: 428/403
• CPC Class Codes: A61K 9/143 with inorganic compounds
• CPC Class Codes: A61K 9/146 with organic macromolecular compounds
• CPC Class Codes: A61K 9/2077 Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
• CPC Class Codes: Y10T 428/2982 Particulate matter [e.g., sphere, flake, etc.]
• CPC Class Codes: Y10T 428/2991 Coated
• CPC Class Codes: Y10T 428/2993 Silicic or refractory material containing [e.g., tungsten oxide, glass, cement, etc.]
• CPC Class Codes: Y10T 428/2995 Silane, siloxane or silicone coating
• CPC Class Codes: Y10T 428/2996 Glass particles or spheres
• CPC Class Codes: Y10T 428/2998 including synthetic resin or polymer

Abstract

This invention relates to an impregnated powder for increasing the bioavailabilty and/or the solubility of at least one active principle comprising a solid, inert support in a particle form impregnated by a liquid medium comprising a hydrophobic phase and optionally a hydrophilic phase, at least one surfactant and at least one active principle dissolved in at least one of said phases, wherein said active principle(s) is(are) also present in at least one of said phases in the form of a suspension.

Such an impregnated powder is used as a base for various preparations in the pharmaceutical, parapharmaceutical and cosmetic field, in the food complement field and in the food processing industry.

Claims

1. An impregnated powder for increasing the bioavailability and/or the solubility of at least one active principle comprising a solid inert support, in a particle form impregnated by a liquid medium comprising a hydrophobic phase and a hydrophilic phase, at least one surfactant and at least one active principle wherein said active principle(s) is (are) dissolved in one of said hydrophilic or hydrophobic phases, and in the form of a suspension in the other one of said phases, wherein the phase in which the active principle(s) is (are) dissolved is an active principle saturated solution.

2. An impregnated powder according to claim 1, wherein the liquid medium moreover comprises at least one co-surfactant.

3. An impregnated powder according to claim 1, wherein the co-surfactant(s) is (are) selected from the group consisting of alcohols, glycol ethers, glycol and the derivatives thereof, propylene glycol and the derivatiyes thereof, lauryl esters of propylene glycol, polyglycerol and the derivatives thereof, oleyl esters of polyglycerol and ethyldiglycol.

4. An impregnated powder according to claim 1, wherein the surfactant(s) is (are) selected from the group consisting of non ionic, anionic, cationic and amphiphilic surfactants.

5. An impregnated powder according to claim 1, wherein the surfactant(s) is (are) at least 1%, based on the weight of the liquid medium.

6. An impregnated powder according to claim 1, wherein the hydrophobic phase of the liquid medium is selected from the group consisting of vegetable oils mineral oils, animal oils, synthetic oils, monoglycerides, diglycerides, triglycerides, fatty alcohols and derivatives thereof, polyol esters, liquid paraffin, long chain hydrocarbons, tocopherol and derivatives thereof, aliphatic fatty acids, fatty acid esters, silicone oils, phospholipid compounds and derivatives thereof, and mixtures thereof.

7. An impregnated powder according to claim 1, wherein the hydrophilic phase of the liquid medium is selected from the group consisting of water, hydroalcoholic mixtures, saline aqueous solutions, buffered aqueous solutions, water-polyethylene glycol mixtures, water-glycerol mixtures, glucose aqueous solutions and water-propylene glycol mixtures.

8. An impregnated powder according to claim 1, wherein the active material(s) is (are) selected from the group consisting of hydrosoluble, liposoluble and amphiphilic active materials.

9. A dry impregnated powder according to claim 1, wherein the active material(s) is (are) selected from the group consisting of pharmaceutical agents, parapharmaceutical agents, cosmetic agents, and food ingredients.

10. An impregnated powder according to claim 9, wherein the active material(s) is (are) selected from the group consisting of active materials used in the following pharmacotherapeutic families:

allergology, anesthesia/resuscitation, cancerology and hematology, cardiology and angiology, contraception and pregnancy interruption, dermatology, endocrinology, gastroentero-pathology, gynecology, immunology, infectiology, metabolism and nutrition, neurology/psychiatry, ophthalmology, otorhinolaryngology, pneumology, rhumatology, stomatology, toxicology, urology/nephrology, as well as analgesic and antispasmodic drugs, anti-inflammatory drugs, the contrast products used in radiology, hemostatics and blood treatment products and derivatives thereof.

11. An impregnated powder according to claim 1, wherein the liquid medium contains from 0.001% to 70% by weight of active material based on the total weight of the liquid system.

12. An impregnated powder according to claim 1, wherein the liquid medium moreover comprises at least one adhesive agent.

13. An impregnated powder according to claim 1, wherein the liquid medium moreover comprises at least one penetration builder.

14. An impregnated powder according to claim 1, wherein the liquid medium moreover comprises at least one thermoreversible polymer.

15. An impregnated powder according to claim 1, wherein the liquid medium is 1% to 99% based on the total weight of the impregnated powder.

16. An impregnated powder according to claim 1, wherein the inert solid support is selected from the group consisting of natural silicas, silica gels, fumed silicas, precipitated silicas, clays, talc, magnesium hydroxide, aluminum hydroxide, magnesium oxide, maltodextrins, cyclodextrins, cellulose derivatives and mixtures thereof.

17. An impregnated powder according to claim 1, wherein it comprises one or more builders selected from the group consisting of flavoring agents, perfumes, essential oils, dyes, antioxidants, preservatives, sweeteners and fillers.

21. An impregnated powder according to claim 1, wherein the impregnated powder is supplied in a packaging adapted to the administration of all or part of such an impregnated powder.

22. An impregnated powder according to claim 1, wherein all or part of such an impregnated powder is provided in a form selected from the group consisting of bags, stick-packs, wipes, capsules, pressurized flasks, non pressurized flasks, and powder sprays provided through a nasal, oral or vaginal route.

23. An impregnated powder according to claim 1, wherein all or part of such an impregnated powder is provided in a form selected from the group consisting of bare or blistered tablets, sugar-coated tablets, coated tablets (soluble coating, pH-dependent or independent coating, with a gastric, intestinal or other release), matricial tablets, osmotic tablets, multilayered tablets, effervescent tablets, dual core tablets, floating tablets, forms with gastric residence and/or floating forms, mucoadhesive forms, capsules, powders, multiparticle forms such as granules, coated microgranules (sugar-coated, with a soluble, pH-dependent coating) or not coated microgranules, mucoadhesive forms, and atomized solids.

24. An impregnated powder according to claim 1, wherein it is as a galenic form with a release profile selected from the group consisting of immediate, modified, delayed, bimodal and pulsed release.

25. A method of preparing a pharmaceutical dosage form comprising the impregnated powder according to claim 1, comprising:

providing said impregnated powder;

providing one or more pharmaceutically-acceptable excipients; and

forming a pharmaceutical dosage form selected from the group consisting of bare or blistered tablets, sugar-coated tablets, coated tablets (soluble coating, pH-dependent or independent coating, with a gastric, intestinal or other release), matricial tablets, osmotic tablets, multilayered tablets, effervescent tablets, dual core tablets, floating tablets, forms with gastric residence and/or floating forms, mucoadhesive forms, capsules, powders, multiparticle forms such as granules, coated microgranules (sugar-coated, with a soluble, pH-dependent coating) or not coated microgranules, mucoadhesive forms and atomized solids by combining said one or more pharmaceutically-acceptable excipients with the impregnated powder of claim 1.

26. An impregnated powder according to claim 5, wherein the surfactant(s) is (are) 2% to 70%, based on the weight of the liquid microemulsion.

27. An impregnated powder according to claim 26, wherein the surfactant(s) is (are) 10% to 60%, based on the weight of the liquid microemulsion.

28. An impregnated powder according to claim 11, wherein the liquid medium contains from 0.5% to 60% by weight of active material based on the total weight of the liquid system.

29. An impregnated powder according to claim 28, wherein the liquid medium is 20% to 90%, based on the total weight of the impregnated powder.

30. An impregnated powder according to claim 29, wherein the liquid medium is 40% to 90% based on the total weight of the impregnated powder.

31. An impregnated powder according to claim 30, wherein the liquid medium is 50% to 80% based on the total weight of the impregnated powder.

18. A method for producing an impregnated powder comprising the steps of:

obtaining a liquid medium comprising an hydrophilic phase and a hydrophobic phase, at least one surfactant and at least one dissolved active principle in at least one of said phases and present in at least one of said phases in the form of a suspension, wherein the phase in which the active principle(s) is (are) dissolved is an active principle saturated solution;

mixing a suitable amount of the liquid medium and a suitable amount of an inert solid support in a particle form liable to adsorb the liquid medium; and

recovering an impregnated powder.

19. A method according to claim 18, wherein the liquid medium is obtained by solubilizing an amount of active principle(s) in one of said phases, mixing to the phase containing the dissolved active principle(s) in the other of said phases, and adding an additional amount of active principle(s) to the mixture of two phases in order to obtain a suspension.

20. A method according to claim 18, wherein the liquid medium is obtained by mixing the two phases and adding an amount of active principle(s) sufficient to obtain a dissolution of the active principle(s) in at least one of the phases and a suspension of the active principle(s) in at least one of the other phases.