.

Pharmaceutical Business Intelligence

  • Anticipate P&T budget requirements
  • Evaluate market entry opportunities
  • Find generic sources and suppliers
  • Predict branded drug patent expiration

► Plans and Pricing

Upgrade to enjoy subscriber-only features like email alerts and data export. See the Plans and Pricing

DrugPatentWatch Database Preview

Details for Patent: 6,048,548

« Back to Dashboard

Details for Patent: 6,048,548

Title: Sustained release heterodisperse hydrogel systems-amorphous drugs
Abstract:Sustained release oral solid dosage forms comprising agglomerated particles of a therapeutically active medicament in amorphous form, a gelling agent, an ionizable gel strength enhancing agent and an inert diluent, as well as processes for preparing and using the same are disclosed. The sustained release oral solid dosage forms are useful in the treatment of hypertension in human patients.
Inventor(s): Baichwal; Anand (Wappingers Falls, NY)
Assignee: Edward Mendell Co., Inc. (Patterson, NY)
Filing Date:Jun 29, 1998
Application Number:09/106,438
Claims:1. A method of preparing a bioavailable sustained release oral dosage form comprising

combining (i) a medicament in amorphous form, (ii) a wetting agent and (iii) a sustained release excipient to obtain a mixture; said sustained release excipient comprising a gelling agent, an ionizable gel enhancing agent, and an inert diluent, the ratio of inert diluent to gelling agent being from about 1:8 to about 8:1; said ionizable gel strength enhancing agent increasing the gel strength of a gel formed when said solid dosage form is exposed to an aqueous solution and said gelling agent comprising xanthan gum and locust bean gum in a ratio of said xanthan gum to said locust bean gum of from about 1:3 to about 3:1;

thereafter drying and milling said mixture to obtain a sustained release product; and

then forming said sustained release product into orally administrable unit doses.

2. The method of claim 1, wherein the medicament has an aqueous solubility of less than 10 g/liter.

3. The method of claim 1, wherein the wetting agent is polyethylene glycol.

4. The method of claim I, wherein said medicament is selected from the group consisting of nifedipine, nimodipine, nivadipine, nitrendipine, nisolidipine, niludipine, nicardipine and felodipine.

5. The method of claim 4 wherein said medicament is nifedipine.

6. The method of claim 3 wherein the polyethylene glycol is mixed with water to form a polyethylene glycol-water slurry prior to its being, combined with the medicament and the sustained release excipient.

7. The method of claim 1, wherein said, gelling agent, ionizable gel enhancing agent and inert diluent are premanufactured as a sustained release excipient.

8. The method of claim 1, further comprising adding a hydrophobic material to the sustained release excipient prior to combining the medicament, wetting agent and sustained release excipient.

9. The method of claim 1, further comprising dissolving the medicament in the wetting agent and then adding the gelling agent, ionizable gel enhancing agent, inert diluent and a hydrophobic material to the resulting combination.

10. The method of claim 1, wherein said gelling agent further comprises an agent selected from the group consisting of alginates, carrageenan, pectin, guar gum, xanthan gum, locust bean gum, modified starch, a cellulosic material and mixtures of any of the foregoing.

11. The method of claim 10, wherein said cellulosic material is selected from the group consisting of hydroxypropylmethylcellulose, methylcellulose, sodium carboxymethylcellulose and hydroxypropyl cellulose and mixtures of any of the foregoing.

12. The method of claim 1, wherein said ionizable gel strength enhancing agent is selected from the group consisting of monovalent, divalent and multivalent organic or inorganic salts and mixture thereof.

13. The method of claim 1, wherein said ionizable gel strength enhancing agent is selected from the group consisting of an alkali metal sulfate, alkali metal chloride, alkali metal borate, alkali metal bromide, alkali metal citrate, alkali metal acetate, alkali metal lactate, alkaline earth metal sulfate, alkaline earth metal chloride, alkaline earth metal borate, alkaline earth metal bromide, alkaline earth metal citrate, alkaline earth metal acetate, alkaline earth metal lactate and mixtures thereof.

14. The method of claim 1, wherein said composition further comprises an amount of a pharmaceutically acceptable hydrophobic material effective to slow the hydration of the gelling agent when said solid dosage form is exposed to gastrointestinal fluid.

15. A method of treating a patient comprising administering a dosage form prepared according to claim 1 to a patient in need of antihypertensive treatment.

16. A method of preparing a bioavailable sustained release oral dosage form comprising:

combining a hydrophobic material and a sustained release excipient comprising a gelling agent, an ionizable gel enhancing agent and an inert diluent, the ratio of inert diluent to gelling agent being from about 1:8 to about 8:1, said ionizable gel strength enhancing agent increasing the gel strength of a gel formed when said solid dosage form is exposed to an aqueous solution, and said gelling agent comprising xanthan gum and locust bean gum in a ratio of said xanthan gum to said locust bean gum of from about 1:3 to about 3:1;

combining said hydrophobic material and sustained release excipient with (i) a medicament in amorphous form and (ii) a wetting agent to obtain a mixture;

drying and milling said mixture to obtain a sustained release product; and

then forming said sustained release product into orally administrable unit doses.

17. A method of preparing a bioavailable sustained release oral dosage form comprising:

dissolving a medicament in amorphous form in a wetting agent and then adding (i) a hydrophobic material and (ii) a sustained release excipient comprising a gelling agent, an ionizable gel enhancing agent and an inert diluent to obtain a mixture; and thereafter drying and milling said mixture to obtain a sustained release product; the ratio of inert diluent to gelling agent being from about 1:8 to about 8:1, said ionizable gel strength enhancing agent increasing the gel strength of a gel formed when said solid dosage form is exposed to an aqueous solution and said gelling agent comprising xanthan gum and locust bean gum in a ratio of said xanthan gum to said locust bean gum of from about 1:3 to about 3:1; and

then forming said sustained release product into orally administrable unit doses.

18. A method of preparing a bioavailable sustained release oral dosage form comprising:

dry blending a medicament in amorphous form and a sustained release excipient to obtain a sustained release product; said sustained release excipient comprising a gelling agent comprising xanthan gum and locust bean gum in a ratio of said xanthan gum to said locust bean gum of from about 1:3 to about 3:1, an ionizable gel enhancing agent which increases the gel strength of a gel formed when said solid dosage form is exposed to an aqueous solution, and an inert diluent, the ratio of inert diluent to gelling agent being from about 1:8 to about 8:1; and

then forming said sustained release product into orally administrable unit doses.

19. The method of claim 18, further comprising admixing a wetting agent with the dry blended mixture of medicament, gelling agent, ionizable gel enhancing agent and inert diluent to form a wetting agent-based slurry, and then drying and milling the resultant mixture.

20. The method of claim 19, wherein said gelling agent, ionizable gel enhancing agent and inert diluent are premanufactured as a sustained release excipient.

21. The method of claim 1, wherein the wetting agent comprises a pharmaceutically acceptable solid wetting agent.

22. The method of claim 21, wherein the wetting agent is a mixed surfactant/wetting agent system.

23. The method of claim 22, wherein the mixed surfactant/wetting agent system is selected from the group consisting of sodium lauryl sulfate/solid polyethylene glycol (PEG) 6000 and sodium lauryl sulfate/solid PEG 6000/stearic acid.

24. The method of claim 1, wherein the wetting agent is included in an amount from about 5% to about 10%, by weight, of the sustained release product.

25. The method of claim 1, wherein the medicament is nifedipine and the wetting agent is included in an amount from about 2% to about 20%, by weight, of said sustained release product.

26. The method of claim 1, wherein the unit doses of a sustained release oral solid dosage form are coated with a hydrophobic polymer to a weight gain from about 1% to about 20%, by weight.

27. The method of claim 1, wherein said sustained release excipient comprises from about 10 to about 99 percent by weight of a gelling agent comprising a heteropolysaccharide gum and a homopolysaccharide gum, from about 1 to about 20 percent by weight of an ionizable gel strength enhancing agent, and from about 0 to about 89 percent by weight of an inert pharmaceutical diluent.

28. The method of claim 1, wherein the sustained release excipient comprises from about 10 to about 75 percent gelling agent, from about 2 to about 15 percent ionizable gel strength enhancing agent, and from about 30 to about 75 percent inert diluent.

29. The method of claim 1, wherein the sustained release excipient comprises from about 30 to about 75 percent gelling agent, from about 5 to about 10 percent ionizable gel strength enhancing agent, and from about 15 to about 65 percent inert diluent.

30. The method of claim 14, wherein the hydrophobic material is selected from the group consisting of an alkylcellulose, hydrophobic cellulosic materials, polymers or copolymers derived from acrylic or methacrylic acid esters, copolymers of acrylic and methacrylic acid esters, zein, waxes, shellac, and hydrogenated vegetable oils.

31. The method of claim 14, wherein the pharmaceutically acceptable hydrophobic material is included in the sustained release excipient in an amount from about 1 to about 20 percent by weight.

32. The method of claim 14, wherein the solvent for the hydrophobic material is ethanol.

33. The method of claim 14, wherein the hydrophobic material is ethyl cellulose.

34. The method of claim 1, further comprising the step of coating the orally administrable unit doses with a hydrophobic coating.

35. The method of claim 34, wherein the oral solid dosage form is coated with the hydrophobic coating to a weight gain of from about 1 to about 20 percent.

36. The method of claim 34, wherein the oral solid dosage form is coated with an enteric coating material in addition to the hydrophobic coating.

37. The method of claim 1, wherein the oral solid dosage form is coated with an enteric coating material.

38. The method of claim 37, wherein the enteric coating material is selected from the group consisting of cellulose acetate phthalate, hydroxypropylmethylcellulose phthalate, polyvinylacetate phthalate, methacrylic acid copolymer, shellac, hydroxypropylmethylcellulose succinate, cellulose acetate trimellitate, and mixtures of any of the foregoing.

39. The method of claim 1, wherein the oral solid dosage form is coated with a hydrophilic coating.

40. The method of claim 34, wherein the oral solid dosage form is coated with a hydrophlic coating in addition to the hydrophobic coating.

41. The method of claim 37, wherein the oral solid dosage form is coated with a hydrophilic coating in addition to the enteric coating.

42. The method of claim 36, wherein the oral solid dosage form is coated with a hydrophilic coating in addition to the hydrophobic coating and enteric coating.

43. The method of claim 39, wherein the hydrophilic coating is hydroxypropylmethylcellulose.

44. The method of claim 16, wherein the hydrophobic material is ethyl cellulose.

45. The method of claim 17, wherein the hydrophobic material is ethyl cellulose.
« Back to Dashboard

For more information try a trial or see the database preview and plans and pricing

How are People Using DrugPatentWatch?

Drugs may be covered by multiple patents or regulatory protections. All trademarks and applicant names are the property of their respective owners or licensors. Although great care is taken in the proper and correct provision of this service, thinkBiotech LLC does not accept any responsibility for possible consequences of errors or omissions in the provided data. The data presented herein is for information purposes only. There is no warranty that the data contained herein is error free. thinkBiotech performs no independent verifification of facts as provided by public sources nor are attempts made to provide legal or investing advice. Any reliance on data provided herein is done solely at the discretion of the user. Users of this service are advised to seek professional advice and independent confirmation before considering acting on any of the provided information. thinkBiotech LLC reserves the right to amend, extend or withdraw any part or all of the offered service without notice.

`abc