.

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: 5,580,578

« Back to Dashboard

Details for Patent: 5,580,578

Title: Controlled release formulations coated with aqueous dispersions of acrylic polymers
Abstract:A stable solid controlled release formulation having a coating derived from an aqueous dispersion of a hydrophobic acrylic polymer includes a substrate including an active agent selected from the group consisting of a systemically active therapeutic agent, a locally active therapeutic agent, a disinfecting and sanitizing agent, a cleansing agent, a fragrance agent and a fertilizing agent, overcoated with an aqueous dispersion of the plasticized water-insoluble acrylic polymer. The formulation provides a stable dissolution of the active agent which is unchanged after exposure to accelerated storage conditions.
Inventor(s): Oshlack; Benjamin (New York, NY), Pedi, Jr.; Frank (Yorktown Heights, NY), Chasin; Mark (Manalapan, NJ)
Assignee: Euro-Celtique, S.A. (LU)
Filing Date:Jul 27, 1993
Application Number:08/097,558
Claims:1. A controlled release formulation comprising a substrate containing an active agent in an amount sufficient to provide a desired effect in an environment of use, said substrate coated with a plasticized aqueous dispersion consisting essentially of ammoniomethacrylate copolymers which are copolymerizates of acrylic and methacrylic esters having a low content of quaternary ammonium groups in an amount sufficient to obtain a controlled release of said active agent when said formulation is exposed to an environmental fluid, said coated substrate being cured at a temperature greater than the glass transition temperature of the aqueous dispersion of said plasticized water-insoluble acrylic polymer for about 24 to about 60 hours until a curing endpoint is reached at which said cured coated substrate provides a stabilized dissolution of said active agent which is unchanged after exposure to accelerated storage conditions, said endpoint being determined by comparing the dissolution profile of the formulation immediately after curing to the dissolution profile of the formulation after exposure to accelerated storage conditions of at least one month at a temperature of 37.degree. C. and at a relative humidity of 80%.

2. The formulation of claim 1, wherein said water-insoluble acrylic polymer is comprised of monomers selected from the group consisting of an ester of acrylic acid, an ester of methacrylic acid, an alkyl ester of acrylic acid, an alkyl ester of methacrylic acid, and mixtures of any of the foregoing.

3. The formulation of claim 1, wherein said substrate is coated to a weight gain from about 2% to about 50%.

4. The formulation of claim 1, wherein said active agent is selected from the group consisting of a systemically active therapeutic agent, a locally active therapeutic agent, a disinfecting agent, a cleansing agent, a fragrance, a fertilizing agent, a deodorant, a dye, an animal repellant, an insect repellant, a pesticide, a herbicide, a fungicide, and a plant growth stimulant.

5. The formulation of claim 4, wherein said locally active therapeutic agent is selected from the group consisting of an antifungal agent, an antibiotic, an antiviral agent, a breath freshener, an antitussive agent, an anti-cariogenic agent, an analgesic agent, a local anesthetic, an antiseptic, an anti-flammatory agent, a hormonal agent, an antiplaque agent, an acidity reducing agent, and a tooth desensitizer.

6. The formulation of claim 6, wherein said systemically active therapeutic agent is selected from the group consisting of antihistamines, analgesics, non-steroidal anti-inflammatory agents, gastro-intestinals, anti-emetics, anti-epileptics, vasodilators, anti-tussive agents, expectorants, anti-asthmatics, hormones, diuretics, anti-hypotensives, anti-hypertensives, bronchodilators, antibiotics, antivirals, antihemorrhoidals, steroids, hypnotics, psychotropics, antidiarrheals, mucolytics, sedatives, decongestants, laxatives, vitamins, and stimulants.

7. The formulation of claim 4, wherein said active agent is an opioid analgesic selected from the group consisting of hydromorphone, oxycodone, morphine, levorphanol, methadone, meperidine, heroin, dihydrocodeine, codeine, hydrocodone, tramadol, dihydromorphine, buprenorphine, mixed opiate receptor agonist-antagonists, salts, hydrates and solvents of any of the foregoing, and mixtures of any of the foregoing.

8. The formulation of claim 6, wherein said substrate is a pharmaceutically acceptable bead, and a plurality of said coated, cured beads are placed in a capsule in an amount sufficient to provide an effective controlled release dose when contacted by an aqueous solution.

9. The formulation of claim 1, wherein said substrate is a tablet core.

10. The formulation of claim 6, wherein said formulation provides effective blood levels of said systemically active therapeutic agent for about 24 hours.

11. The formulation of claim 7, wherein said formulation provides effective blood levels of said systemically active therapeutic agent for about 24 hours.

12. The formulation of claim 8, wherein said beads are coated with said aqueous dispersion of water-insoluble acrylic polymer to a weight gain from about 2 to about 25 percent.

13. The formulation of claim 1, wherein said coating is cured for a time period from about 24 to about 48 hours, until said endpoint is reached.

14. The formulation of claim 2, wherein said water-insoluble acrylic polymer comprises a mixture of copolymers of acrylic and methacrylic esters having a molar ratio of ammonium groups to (meth)acrylic esters from about 1:20 to about 1:40.

15. The formulation of claim 2, wherein said water-insoluble acrylic polymer comprises a mixture of a first copolymer of acrylic and methacrylic esters having a molar ratio of ammonium groups to (meth)acrylic esters of about 1:20 and a second copolymer of acrylic and methacrylic esters having a molar ratio of ammonium groups to (meth)acrylic esters of about 1:40, the ratio of said first copolymer to said second copolymer being from about 0:100 to about 100:0.

16. The formulation of claim 1, which provides a stable dissolution of said active agent which is unchanged after exposure to accelerated storage conditions of a temperature of 40.degree. C. and a relative humidity of 75% for 3 months.

17. The formulation of claim 1, which provides a stable dissolution of said active agent which is unchanged after exposure to accelerated storage conditions which are deemed appropriate by the United States Food & Drug Administration for the purpose of according expiration dating for said formulation.

18. The formulation of claim 1, wherein said cured coated substrate, when subjected to in-vitro dissolution after exposure to said accelerated conditions, releases an amount of said active agent which does not vary at any given time point by more than about 15% of the total amount of active agent released when compared to in-vitro dissolution conducted prior to storage.

19. The formulation of claim 1, wherein said cured coated substrate, when subjected to in-vitro dissolution after exposure to said accelerated conditions, releases an amount of said active agent which does not vary at any given time point by more than about 10% of the total amount of active agent released when compared to in-vitro dissolution conducted prior to storage.

20. The formulation of claim 1, wherein said cured coated substrate, when subjected to in-vitro dissolution after exposure to said accelerated conditions, releases an amount of said active agent which does not vary at any given time point by more than about 7% of the total amount of active agent released when compared to in-vitro dissolution conducted prior to storage.

21. The formulation of claim 1, wherein a portion of the amount of said active agent included in said formulation is incorporated into a coating on said substrate.

22. A solid controlled release formulation, comprising a substrate containing an active agent in an amount sufficient to provide a desired effect in an environment of use, said substrate coated with a plasticized aqueous dispersion consisting essentially of ammoniomethacrylate copolymers which are copolymerizates of acrylic and methacrylic esters having a low content of quaternary ammonium groups in an amount sufficient to obtain a controlled release of said active agent when said formulation is exposed to an environmental fluid, said coated substrate being cured at a temperature greater than the glass transition temperature of the plasticized water-insoluble acrylic polymer for about 24 to about 60 hours until an endpoint is reached at which said cured coated substrate, when exposed to an environment of use, releases said active agent in amounts which do not vary at any time point along the dissolution curve by more than about 15% of the total amount of active agent released, when compared to the in-vitro dissolution of said coated substrate prior to curing.

23. The formulation of claim 22, wherein said cured, coated substrate provides the same rate of release immediately after curing to said endpoint, and after subsequent exposure to accelerated storage conditions of one month at a temperature of 37.degree. C. and at a relative humidity of 80%.

24. The formulation of claim 22, wherein said cured, coated substrate provides the same rate of release immediately after curing to said endpoint, and after subsequent exposure to accelerated storage conditions of one month at a temperature of 40.degree. C. and at a relative humidity of 75%.

25. The formulation of claim 22, wherein said water-insoluble acrylic polymer is comprised of monomers selected from the group consisting of an ester of acrylic acid, an ester of methacrylic acid, an alkyl ester of acrylic acid, an alkyl ester of methacrylic acid, and mixtures of any of the foregoing.

26. The formulation of claim 22, wherein said substrate is coated to a weight gain from about 2% to about 50%.

27. The formulation of claim 22, wherein said active agent is selected from the group consisting of a systemically active therapeutic agent, a locally active therapeutic agent, a disinfecting agent, a cleansing agent, a fragrance, a fertilizing agent, a deodorant, a dye, an animal repellant, an insect repellant, a pesticide, a herbicide, a fungicide, and a plant growth stimulant.

28. The formulation of claim 27, wherein said locally active therapeutic agent is selected from the group consisting of an antifungal agent, an antibiotic, an antiviral agent, a breath freshener, an antitussive agent, an anti-cariogenic agent, an analgesic agent, a local anesthetic, an antiseptic, an anti-flammatory agent, a hormonal agent, an antiplaque agent, an acidity reducing agent, and a tooth desensitizer.

29. The formulation of claim 27, wherein said systemically active therapeutic agent is selected from the group consisting of antihistamines, analgesics, non-steroidal anti-inflammatory agents, gastro-intestinals, anti-emetics, anti-epileptics, vasodilators, anti-tussive agents, expectorants, anti-asthmatics, hormones, diuretics, anti-hypotensives, anti-hypertensives, bronchodilators, antibiotics, antivirals, antihemorrhoidals, steroids, hypnotics, psychotropics, antidiarrheals, mucolytics, sedatives, decongestants, laxatives, vitamins, and stimulants.

30. The formulation of claim 27, wherein said substrate is a pharmaceutically acceptable bead, and a plurality of said coated, cured beads are placed in a capsule in an amount sufficient to provide an effective controlled release dose when contacted by an aqueous solution.

31. The formulation of claim 22, wherein said substrate is a tablet core.

32. The formulation of claim 29, wherein said substrate is selected from the group consisting of a tablet core and a plurality of pharmaceutically inert beads, and said cured, coated formulation when administered orally provides effective blood levels of said systemically active therapeutic agent for about 24 hours.

33. The formulation of claim 29, wherein said substrate is selected from the group consisting of a tablet core and a plurality of pharmaceutically inert beads, and said cured, coated formulation when administered orally provides effective blood levels of said systemically active therapeutic agent for about 12 hours.

34. The formulation of claim 32, wherein said active agent is an opioid analgesic selected from the group consisting of hydromorphone, oxycodone, morphine, levorphanol, methadone, meperidine, heroin, dihydrocodeine, codeine, hydrocodone, tramadol, dihydromorphine, buprenorphine, mixed opiate receptor agonist-antagonists, salts, hydrates and solvents of any of the foregoing, and mixtures of any of the foregoing.

35. The formulation of claim 22, wherein said coating is cured for a time period from about 24 to about 48 hours, until said endpoint is reached.

36. A solid controlled release oral dosage formulation, comprising a substrate containing a systemically active therapeutic agent in an amount sufficient to provide a desired therapeutic effect when said formulation is orally administered, said substrate being coated with an aqueous dispersion consisting, essentially of a plasticized copolymer of acrylic and methacrylic acid esters having a permeability which is unaffected by the pH conditions prevailing in the digestive tract, to a weight gain sufficient to obtain a controlled release of said active agent when measured by the USP Paddle or Basket Method at 100 rpm at 900 ml aqueous buffer (pH between 6 and 7.2) at 37.degree. C. from about 0% to about 42.5% (by wt) active agent released after 1 hour, from about 25% to about 55% (by wt) active agent released after 2 hours, from about 45% to about 75% (by wt) active agent released after 4 hours and greater than about 55% (by wt) active agent released after 6 hours, said coated substrate being cured at a temperature greater than the glass transition temperature of said aqueous dispersion of the plasticized acrylic polymer for a time period of about 20 to about 60 hours, said coated substrate when subjected to accelerated storage conditions of at least one month at 40.degree. C./75% RH releasing an amount of said therapeutically active agent upon in-vitro dissolution which does not vary at any given time point by more than about 15% of the total amount of therapeutically active agent released when compared to in-vitro dissolution conducted prior to storage, and when administered orally providing effective blood levels of said systemically active therapeutic agent for at least about 12 hours.

37. The formulation of claim 36, wherein said therapeutically active agent is selected from the group consisting of antihistamines, analgesics, non-steroidal anti-inflammatory agents, gastro-intestinals, anti-emetics, anti-epileptics, vasodilators, anti-tussive agents, expectorants, anti-asthmatics, hormones, diuretics, anti-hypotensives, anti-hypertensives, bronchodilators, antibiotics, antivirals, antihemorrhoidals, steroids, hypnotics, psychotropics, antidiarrheals, mucolytics, sedatives, decongestants, laxatives, vitamins, and stimulants.

38. The formulation of claim 36, wherein said water-insoluble acrylic polymer comprises a mixture of copolymers of acrylic and methacrylic esters having a molar ratio of ammonium groups to (meth)acrylic esters from about 1:20 to about 1:40.

39. The formulation of claim 36, which provides a stable dissolution of said active agent which is unchanged after exposure to accelerated storage conditions of a temperature of 40.degree. C. and a relative humidity of 75% for 3 months.

40. The formulation of claim 37, wherein said active agent is an opioid analgesic selected from the group consisting of hydromorphone, oxycodone, morphine, levorphanol, methadone, meperidine, heroin, dihydrocodeine, codeine, hydrocodone, tramadol, dihydromorphine, buprenorphine, mixed opiate receptor agonist-antagonists, salts, hydrates and solvents of any of the foregoing, and mixtures of any of the foregoing.

41. The formulation of claim 36, wherein said substrate is a pharmaceutically acceptable bead, and a plurality of said coated, cured beads are placed in a capsule in an amount sufficient to provide an effective controlled release dose when said capsule is orally administered.

42. The formulation of claim 40, wherein a portion of the amount of said active agent included in said formulation is incorporated into a coating on said substrate.

43. A solid controlled release oral dosage formulation, comprising a substrate containing a systemically active therapeutic agent in an amount sufficient to provide a desired therapeutic effect when said formulation is orally administered, said substrate being coated with an aqueous dispersion consisting essentially of a plasticized copolymer of acrylic and methacrylic acid esters having a permeability which is unaffected by the pH conditions prevailing in the digestive tract, to a weight gain sufficient to obtain a controlled release of said active agent when measured by the USP Paddle or Basket Method at 100 rpm at 900 ml aqueous buffer (pH between 1.6 and 7.2) at 37.degree. C. from about 0% to about 42.5% (by wt) active agent released after 1 hour, from about 5% to about 60% (by wt) active agent released after 2 hours, from about 15% to about 75% (by wt) active agent released after 4 hours and from about 20% to about 90% (by wt) active agent released after 8 hours, said coated substrate being cured at a temperature greater than the glass transition temperature of said aqueous dispersion of the plasticized acrylic polymer for a time period of about 20 to about 60 hours, said coated substrate when subjected to accelerated storage conditions of at least one month at 40.degree. C./75% RH releasing an amount of said therapeutically active agent upon in-vitro dissolution which does not vary at any given time point by more than about 15% of the total amount of therapeutically active agent released when compared to in-vitro dissolution conducted prior to storage, and when administered orally providing effective blood levels of said systemically active therapeutic agent for about 24 hours.

44. The formulation of claim 43, wherein said systemically active therapeutic agent is selected from the group consisting of antihistamines, analgesics, non-steroidal anti-inflammatory agents, gastro-intestinals, anti-emetics, anti-epileptics, vasodilators, anti-tussive agents, expectorants, anti-asthmatics, hormones, diuretics, anti-hypotensives, anti-hypertensives, bronchodilators, antibiotics, antivirals, antihemorrhoidals, steroids, hypnotics, psychotropics, antidiarrheals, mucolytics, sedatives, decongestants, laxatives, vitamins, and stimulants.

45. The formulation of claim 43, wherein said water-insoluble acrylic polymer comprises a mixture of copolymers of acrylic and methacrylic esters having a molar ratio of ammonium groups to (meth)acrylic esters from about 1:20 to about 1:40.

46. The formulation of claim 43, which provides a stable dissolution of said active agent which is unchanged after exposure to accelerated storage conditions of a temperature of 40.degree. C. and a relative humidity of 75% for 3 months.

47. The formulation of claim 44, wherein said agent is an opioid analgesic selected from the group consisting of hydromorphone, oxycodone, morphine, levorphanol, methadone, meperidine, heroin, dihydrocodeine, codeine, hydrocodone, tramadol, dihydromorphine, buprenorphine, mixed opiate receptor agonist-antagonists, salts, hydrates and solvents of any of the foregoing, and mixtures of any of the foregoing.

48. The formulation of claim 43, wherein said substrate is a pharmaceutically acceptable bead, and a plurality of said coated, cured beads are placed in a capsule in an amount sufficient to provide an effective dose when said capsule is orally administered.

49. The formulation of claim 43, wherein a portion of the amount of said active agent included in said formulation is incorporated into a coating on said substrate.

50. A solid controlled release formulation, comprising a substrate containing an active agent in an amount sufficient to provide a desired effect in an environment of use, said substrate coated with an aqueous dispersion consisting essentially of a plasticized water-insoluble acrylic polymer comprised of monomers selected from the group consisting of an ester of acrylic acid, an ester of methacrylic acid, an alkyl ester of acrylic acid, an alkyl ester of methacrylic acid, and mixtures of any of the foregoing, in an amount sufficient to obtain a controlled release of said active agent when said formulation is exposed to an environmental fluid, said coated substrate including at least one passageway through said coating through which said active agent is released, said coated substrate being cured at a temperature greater than the glass transition temperature of the plasticized aqueous dispersion for a time period of about 20 to about 60 hours until an endpoint is reached at which said cured coated substrate, when subjected to in-vitro dissolution, releases said active agent in amounts which do not vary at any time point along the dissolution curve by more than about 15% of the total amount of active agent released, when compared to the in-vitro dissolution of said coated substrate prior to curing.

51. A controlled release dosage form, comprising a solid substrate comprising an effective amount of a therapeutically active agent, said solid substrate coated with an aqueous dispersion consisting essentially of a copolymer of acrylic and methacrylic acid esters having a low content of quaternary ammonium groups, in an amount effective to provide a controlled release of said therapeutically active agent when said coated substrate is exposed to gastrointestinal fluid, said coated substrate being cured at a temperature greater than the glass transition temperature of said aqueous dispersion of the plasticized acrylic polymer for a time period of about 20 to about 60 hours, said coated substrate when subjected to in-vitro dissolution after exposure to accelerated storage conditions of at least one month at 40.degree. C./75% RH releasing an amount of said therapeutically active agent which does not vary at any given dissolution time point by more than about 15% of the total amount of therapeutically active agent released when compared to in-vitro dissolution conducted prior to storage.

52. The controlled release dosage form of claim 51 which is administered once a day.

53. The controlled release dosage form of claim 51 which is administered twice a day.

54. The controlled release dosage form of claim 51 wherein said substrate comprises a pharmaceutically acceptable inert bead upon which said therapeutically active agent is coated and a plurality of said coated beads are placed in a capsule to provide said effective amount of said therapeutically active agent.

55. The controlled release dosage form of claim 51 which is a coated tablet.

56. The controlled release dosage form of claim 51, wherein said therapeutically active agent is an opioid analgesic selected from the group consisting of hydromorphone, oxycodone, morphine, levorphanol, methadone, meperidine, heroin, dihydrocodeine, codeine, dihydromorphine, buprenorphine, salts thereof, and mixtures thereof.
« Back to Dashboard

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

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