Nova Patents
CA2537103C

Once daily dosage forms of trospium

Abstract

A pharmaceutical composition of a pharmaceutically acceptable trospium salt, with upon administration to a human patient generates an average steady stat e blood levels of trospium with a minimum (Cmin) and maximum (Cmax) blood leve ls of about 0.5-2.5 ng/ml and about 2.0-6.0 ng/ml, respectively.

CA2537103C, drawing sheet 1
Sheet 1 of 15

Term

Term ended

Expired 4 November 2024, 1.9 years ago.

  1. Priority
  2. Filed
  3. Granted
  4. Expired
  5. Today

100 claims: 24 independent, 76 dependent

  1. 1
    CA 02537103 2009-09-10 50399-18(S) CLAIMS :1. An oral pharmaceutical composition comprising (1) between 25 mg and 80 mg of trospium chloride and (2) at least one component selected from a delayed release (DR) component comprising an enteric polymer that dissolves at pH above 4.5, and an extended release (XR) component comprising from 1% to 40% of a release controlling polymer, wherein at least a portion of said trospium chloride is contained in said at least one component whereby at a once daily dosage the composition provides steady state blood levels of trospium of a minimum of about 0.5 ng/ml and a maximum of about 6.0 ng/ml.
  2. 20
    The composition of any one of claims 7 to 16, which is a layered tablet, wherein each layer contains one of the components.
  3. 21
    The composition of any one of claims 7 to 16, which is a layered pellet, wherein either or both said DR and XR portion comprises the core of the pellet, and the IR portion surrounds the core.
  4. 22
    Use of the trospium composition as defined in claim 1, in the manufacture of a medicament which provides a daily dose for treating a urinary incontinence disease or condition in a mammal. CA 02537103 2009-09-10 50399-18(S)
  5. 23
    Use of a daily dose of the trospium composition as defined in claim 1, for treating a urinary incontinence disease or condition in a mammal, for at least a time sufficient to ameliorate the disease or condition.
  6. 24
    The use of claim 22 or 23, wherein the mammal is a human.
  7. 25
    The use of claim 22 or 23, wherein about 60 mg trospium chloride is present in ' the composition.
  8. 26
    The use of claim 22 or 23, which composition comprises an immediate release component containing no more than about 20 mg trospium chloride.
  9. 39
    42. A pharmaceutical composition for a once-a-day administration of trospium comprising (1) a total amount of trospium chloride which is less than 80 mg and (2) at least one component selected from an extended release (XR) component comprised of extended release particulates comprising from 1% to 40% of a release controlling polymer;and a delayed release (DR) component comprised of delayed release particulates comprising an enteric polymer that dissolves at pH above 4.5, wherein at least a portion of said trospium chloride is contained in the particulates of said at least one component whereby once-a-day administration of said pharmaceutical composition provides steady state blood levels of trospium that are substantially equivalent to steady state blood levels of trospium achieved with twice daily administration of 20 mg immediate release trospium chloride tablets .
  10. 53
    56. Use of a once-a-day formulation comprising a therapeutically effective amount of trospium chloride in the form of at least one component selected from a delayed release (DR) component comprising an enteric polymer that dissolves at pH above 4.5, and an extended release (XR) component comprising from 1% to 40% of a release controlling polymer, which provides steady state blood levels of trospium substantially equivalent to steady state blood levels of trospium achieved with twice daily administration CA 02537103 2009-09-10 50399-18(S) of 20 mg immediate release trospium chloride tablets and with a lessening of side effects, in the manufacture of a medicament for treating a mammal suffering from overactive bladder that would benefit from a once daily administration of a therapeutically effective amount of trospium chloride.
  11. 54
    57. Use of a once-a-day formulation comprising a therapeutically effective amount of trospium chloride in the form of at least one component selected from a delayed release (DR) component comprising an enteric polymer that dissolves at pH above 4.5, and an extended release (XR) component comprising from 1% to 40% of a release controlling polymer, which provides steady state blood levels of trospium substantially equivalent to steady state blood levels of trospium achieved with twice daily administration of 20 mg immediate release trospium chloride tablets and with a lessening of side effects, for treating a mammal suffering from overactive bladder that would benefit from a once daily administration of a therapeutically effective amount of trospium chloride.
  12. 55
    58. Use, for treating overactive bladder, of a pharmaceutical composition comprising a therapeutically effective amount of trospium chloride, in a delayed release formulation of trospium chloride, which releases trospium chloride at a pH of about 7.0 for enteral administration, and a carrier, wherein the pharmaceutical composition provides steady state blood levels of trospium of a minimum of about 0.5 ng/ml and a maximum of about 6.0 ng/ml.
  13. 56
    59. Use, for treating overactive bladder, of a pharmaceutical composition comprising a therapeutically effective amount of trospium chloride, in a delayed release formulation of trospium chloride, which releases trospium CA 02537103 2009-09-10 50399-18(S) chloride in the lower intestine for enteral administration, and a carrier, wherein the pharmaceutical composition provides steady state blood levels of trospium of a minimum of about 0.5 ng/ml and a maximum of about 6.0 ng/ml.
  14. 57
    60. Use, for treating overactive bladder, of a pharmaceutical composition comprising a therapeutically effective amount of trospium chloride, in a delayed release formulation of trospium chloride, which releases trospium chloride in the colon for enteral administration, and a carrier, wherein the pharmaceutical composition provides steady state blood levels of trospium of a minimum of about 0.5 ng/ml and a maximum of about 6.0 ng/ml.
  15. 58
    61. A pharmaceutical composition comprising from 25 to 80 mg of trospium chloride in which at least a portion of said trospium chloride is contained in a delayed release formulation, which comprises an enteric polymer that dissolves at a pH of about 7.0, releasing trospium chloride, wherein the pharmaceutical composition provides steady state blood levels of trospium of a minimum of about 0.5 ng/ml and a maximum of about 6.0 ng/ml.
  16. 59
    62. A pharmaceutical composition comprising from 25 to 80 mg trospium chloride in which at least a portion of said trospium chloride is contained in a delayed release formulation, which comprises an enteric polymer that dissolves in the lower intestine, colon, or both, releasing trospium chloride, wherein the pharmaceutical composition provides steady state blood levels of trospium of a minimum of about 0.5 ng/ml and a maximum of about 6.0 ng/ml.
  17. 60
    63. A process of preparation of a once daily dosage unit of trospium chloride, which will give steady state blood levels of trospium of a minimum of about 0.5 ng/ml and CA 02537103 2009-09-10 50399-18(S) a maximum of about 6.0 ng/ml, comprising the steps of :1. preparing at least one component selected from an extended release (XR) component and a delayed release (DR) component;2. optionally, combining the result of step 1 with at least one component selected from an XR component, a DR component and an immediate release (IR) component;and 3. encapsulating the result of step 1 or step 2 into a capsule, wherein the total dose of trospium chloride is less than about 80 mg.
  18. 69
    73. A once daily dosage form of trospium chloride comprising the composition as defined in any one of claims 1 to 16, 39 to 55, 61 and 62.
  19. 71
    75. An oral pharmaceutical composition of trospium comprising 25 to 80 mg of trospium chloride and a carrier, wherein at least part of the trospium chloride is contained in an extended release (XR) component or in a delayed release (DR) component, and wherein said composition at a once daily dosage provides steady state blood levels of CA 02537103 2009-09-10 • 50399-18(S) trospium of a minimum of about 0.5,ng/ml and a maximum of about 6.0 ng/ml, for use in treating a bladder dysfunction in a mammal.
  20. 72
    76. An oral pharmaceutical composition of trospium comprising at least one component selected from a delayed release (DR) component and an extended release (XR) component, and a carrier, wherein said composition contains between 25 mg and 80 mg of trospium chloride and at a once daily dosage provides steady state blood levels of trospium of a minimum of about 0.5 ng/ml and a maximum of about 6.0 ng/ml, while minimizing the occurrence of adverse side effects as compared to an immediate release formulation containing 40 mg of trospium chloride.
  21. 95
    99. An oral pharmaceutical composition of trospium, containing a once daily dose of trospium chloride and comprising a combination of a delayed release (DR) component comprising an enteric polymer that dissolves at pH above 4.5, and an extended release (XR) component comprising from CA 02537103 2009-09-10 50399-18(S) 1% to 40% of a release controlling polymer, wherein said DR component is composed of enteric coated pellets consisting essentially of:1. trospium chloride, 2. a sugar core, 3. hydroxypropyl methylcellulose, 4. a coating of the enteric polymer that delays release of the trospium chloride from the pellet for a period of time after administration, 5. triethyl citrate, 6. a protective overcoating, and 7. talc;and said XR component is composed of extended release pellets consisting essentially of: 1. trospium chloride, 2. a sugar core, 3. hydroxypropyl methylcellulose, 4. a surface coating that controls a release profile of the trospium chloride from the pellet after administration, 5. a protective overcoating, and 6. talc;and the once daily dose provides steady state blood levels of trospium of a minimum of about 0.5 ng/ml and a maximum of about 6.0 ng/ml, for use in treating a bladder dysfunction in a mammal.
  22. 96
    100. An oral pharmaceutical composition of trospium, containing a once daily dose of trospium chloride and comprising a mixture of enteric coated pellets and extended release pellets in a ratio of 1:1, the enteric coated pellets consisting essentially of trospium chloride, sugar spheres, hydroxypropyl methylcellulose, methacrylic acid copolymer, triethyl citrate, and talc and wherein the extended release pellets consist essentially of trospium chloride, sugar spheres, hydroxypropyl methylcellulose, ethyl cellulose, OPADRY WHITE™ and talc;and the once daily dose provides steady state blood levels of trospium of a minimum of about 0.5 ng/ml and a maximum of about 6.0 ng/ml, for use in treating a bladder dysfunction in a mammal.
  23. 99
    103. The composition of any one of claims 99 to 102, 5 wherein the bladder dysfunction is overactive bladder (OAB) with symptoms of urge urinary incontinence, urgency and urinary frequency and the composition is in a capsule.
  24. 100
    104. The composition of any one of claims 1 to 21, 42 to 55, 61 and 62, further comprising a carrier. 10 105. The use of claim 56 or 57, wherein the formulation further comprises a carrier. SMART & BIGGAR OTTAWA, CANADA PATENT AGENTS
Independent claims24