Modifying drug release in suspensions of ionic resin systems
The present invention includes compositions and methods for delivering one or more unit dosage units by modifying the release profile of an optionally coated drug-resin complex suspended in an ionic salt solution, wherein the optionally coated drug-resin complex includes one or more active agents loaded on to one or more ion-exchange resin particles, and wherein the release of the one or more active agents is modulated by the one or more ionic salts in solution.
1. A method for modifying the release of at least one pharmacologically active drug from a coated drug-ionic resin in a controlled-release liquid formulation comprising:
adding one or more ionic salts to a controlled-release oral liquid formulation comprising one or more coated drug-ionic resins loaded with one or more pharmacologically active drugs, wherein the addition of said one or more ionic salts increases the amount of at least one pharmacologically active drug released from the drug-ionic resin in the first hour as observed in vitro.
2. The method of claim 1 , wherein the one or more drug-ionic resins are coated with a water-permeable diffusion barrier.
3. The method of claim 1 , wherein one or more pharmacologically active drugs comprise both an immediate release pharmacologically active drug and an extended release pharmacologically active drug.
4. The method of claim 1 , wherein the drug-ionic resins further comprise one or more polymers selected from the group consisting of cellulose, ethylcellulose, methylcellulose, propylcellulose, methoxypropylcellulose, cellulose nitrate, poly(vinyl alcohol), poly(vinyl chloride), polystyrene, polyethylene, polypropylene, poly(ethylene-co-vinyl acetate), poly(hydroxybutyric acid), poly(hydroxyvalerianic acid-co-hydroxybutyric acid), poly(lactic acid), poly(glycolic acid), poly(lactic acid-co-glycolic acid), poly(ε-caprolactones), poly(ε-caprolactone-co-DL-lactic acid), poly(maleic anhydride), polyamides, gelatin, chitosan, collagen, poly(hydroxyalkyl)-L-glutamines, poly(γ-ethyl-L-glutaminate-co-glutamic acid), poly(L-leucine-co-L-aspartic acid), poly(proline-co-glutamic acid), poly(alkyl 2-cyanoacrylates), polyurethanes, poly(methyl methacrylate), poly(methyl methacrylate-co-methacrylic acid) and poly(methacrylate-co-hydroxypropyl methacrylate), polystyrene, polistirex, salts, combinations and mixtures thereof.
5. The method of claim 1 , wherein the ionic salt comprises an inorganic salt.
6. The method of claim 1 , wherein the ionic salt is sodium chloride.
7. The method of claim 1 , wherein the oral liquid formulation comprises a first pharmacologically active drug and a second pharmacologically active drug and the one or more ionic salts modify the release profile of the first pharmacologically active drug but not the second pharmacologically active drug.
8. The method of claim 1 , wherein the one or more pharmacologically active drugs comprises phenylephrine HCl.
9. The method of claim 1 , wherein the one or more pharmacologically active drugs comprises chlorpheniramine maleate.
10. The method of claim 1 , wherein the one or more pharmacologically active drugs comprises dextromethorphan HBr.
11. The method of claim 1 , wherein the one or more pharmacologically active drugs comprises ibuprofen polistirex.
12. The method of claim 1 , wherein the one or more pharmacologically active drugs comprises loratidine polistirex.
13. The method of claim 1 , wherein the one or more pharmacologically active drugs comprises hydrocodone bitartarate polistirex.
14. The method of claim 1 , wherein the one or more pharmacologically active drugs comprises chlorpheniramine maleate and hydrocodone bitartarate polistirex.
15. The method of claim 1 , wherein the one or more pharmacologically active drugs comprises pseudoefedrine HCl.
16. The method of claim 1 , wherein the one or more pharmacologically active drugs comprises promethazine.
17. The method of claim 3 , wherein the one or more pharmacologically active drugs comprises chlorpheniramine maleate and hydrocodone bitartarate polistirex.
18. The method of claim 1 , wherein the release of said amount is measured in a dissolution assay using a USP dissolution apparatus II with 900 ml of 0.1N HCl dissolution medium at pH 1.2.
19. A controlled-release oral liquid composition comprising one or more coated drug-ionic resins loaded with one or more pharmacologically active drugs, wherein the oral liquid composition is improved by increasing the ionic strength of the oral liquid composition by addition of one or more ionic salts whereby the amount of at least one pharmacologically active drug released from the drug-ionic resin in the first hour is increased as observed in vitro.
20. The composition of claim 19 , wherein the one or more drug-ionic resins are coated with a water-permeable diffusion barrier.
21. The composition of claim 19 , wherein one or more pharmacologically active drugs comprise both an immediate release pharmacologically active drug and an extended release pharmacologically active drug.
22. The composition of claim 19 , wherein the drug-ionic resins further comprise one or more polymers selected from the group consisting of cellulose, ethylcellulose, methylcellulose, propylcellulose, methoxypropylcellulose, cellulose nitrate, poly(vinyl alcohol), poly(vinyl chloride), polystyrene, polyethylene, polypropylene, poly(ethylene-co-vinyl acetate), poly(hydroxybutyric acid), poly(hydroxyvalerianic acid-co-hydroxybutyric acid), poly(lactic acid), poly(glycolic acid), poly(lactic acid-co-glycolic acid), poly(ε-caprolactones), poly(ε-caprolactone-co-DL-lactic acid), poly(maleic anhydride), polyamides, gelatin, chitosan, collagen, poly(hydroxyalkyl)-L-glutamines, poly(γ-ethyl-L-glutaminate-co-glutamic acid), poly(L-leucine-co-L-aspartic acid), poly(proline-co-glutamic acid), poly(alkyl 2-cyanoacrylates), polyurethanes, poly(methyl methacrylate), poly(methyl methacrylate-co-methacrylic acid) and poly(methacrylate-co-hydroxypropyl methacrylate), polystyrene, polistirex, salts, combinations and mixtures thereof.
23. The composition of claim 19 , wherein the ionic salt comprises an inorganic salt.
24. The composition of claim 19 , wherein the ionic salt is sodium chloride.
25. The composition of claim 19 , wherein the oral liquid formulation comprises a first pharmacologically active drug and a second pharmacologically active drug and the one or more ionic salts modify the release profile of the first pharmacologically active drug but not the second pharmacologically active drug.
26. The composition of claim 19 , wherein the one or more pharmacologically active drugs comprises chlorpheniramine maleate and hydrocodone bitartarate polistirex.
27. The composition of claim 21 , wherein the one or more pharmacologically active drugs comprises chlorpheniramine maleate and hydrocodone bitartarate polistirex.
28. The composition of claim 19 , wherein the release of said amount is measured in a dissolution assay using a USP dissolution apparatus II with 900 ml of 0.1N HCl dissolution medium at pH 1.2.