Controlled release formulations of opioid and nonopioid analgesics
First Claim
1. A sustained release dosage form for twice daily oral dosing to a human patient, comprising a) an immediate release component;
- b) a sustained release component, wherein said immediate release component and said sustained release component collectively contain a therapeutically effective amount of an opioid analgesic and a therapeutically effective amount of nonopioid analgesic, wherein said amount of nonopioid analgesic is between about 20 and about 100 times said amount of opioid analgesic by weight, and said sustained release component provides sustained release of each of said opioid analgesic and said nonopioid analgesic at rates proportional to each other in said dosage form.
1 Assignment
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Accused Products
Abstract
Sustained release dosage forms for twice daily oral dosing to a human patient for providing relief from pain are provided. The sustained release dosage form comprises an immediate release component and a sustained release component, wherein the immediate release component and the sustained release component collectively contain a therapeutically effective amount of an opioid analgesic and a therapeutically effective amount of nonopioid analgesic. In a preferred embodiment, the nonopioid analgesic is acetaminophen and the opioid analgesic is hydrocodone and pharmaceutically acceptable salts thereof, and in preferred embodiments, the pharmaceutically acceptable salt is bitartrate. The dosage forms produce plasma profiles in a patient characterized by a Cmax for hydrocodone of between about 0.6 ng/mL/mg to about 1.4 ng/mL/mg and an AUC for hydrocodone of between about 9.1 ng*hr/mL/mg to about 19.9 ng*hr/mL/mg (per mg hydrocodone bitartrate administered) and a Cmax for acetaminophen of between about 2.8 ng/mL/mg and 7.9 ng/mL/mg and an AUC for acetaminophen of between about 28.6 ng*hr/mL/mg and about 59.1 ng*hr/mL/mg (per mg acetaminophen administered) after a single dose.
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Citations
121 Claims
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1. A sustained release dosage form for twice daily oral dosing to a human patient, comprising
a) an immediate release component; -
b) a sustained release component, wherein said immediate release component and said sustained release component collectively contain a therapeutically effective amount of an opioid analgesic and a therapeutically effective amount of nonopioid analgesic, wherein said amount of nonopioid analgesic is between about 20 and about 100 times said amount of opioid analgesic by weight, and said sustained release component provides sustained release of each of said opioid analgesic and said nonopioid analgesic at rates proportional to each other in said dosage form. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87)
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88. A sustained release dosage form for twice daily oral dosing to a human patient, comprising
a) an immediate release component; -
b) a sustained release component, wherein said immediate release component and said sustained release component collectively contain a therapeutically effective amount of hydrocodone and a therapeutically effective amount of acetaminophen, wherein said amount of acetaminophen is between about 20 and about 100 times said amount of hydrocodone by weight, and wherein the dosage form produces a Cmax for hydrocodone of between about 0.6 ng/mL/mg to about 1.4 ng/mL/mg and a Cmax for acetaminophen of between about 2.8 ng/mL/mg and 7.9 ng/mL/mg after a single dose. - View Dependent Claims (89)
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90. A sustained release dosage form for twice daily oral dosing to a human patient, comprising
a) an immediate release component; b) a sustained release component, wherein said immediate release component and said sustained release component collectively contain a therapeutically effective amount of hydrocodone and a therapeutically effective amount of acetaminophen, wherein said amount of acetaminophen is between about 20 and about 100 times said amount of hydrocodone by weight, and wherein the dosage form produces an AUC for hydrocodone of between about 9.1 ng*hr/mL/mg to about 19.9 ng*hr/mL/mg and an AUC for acetaminophen of between about 28.6 ng*hr/mL/mg and about 59.1 ng*hr/mL/mg after a single dose. - View Dependent Claims (91)
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92. A sustained release dosage form for twice daily oral dosing to a human patient, comprising
a) an immediate release component; -
b) a sustained release component, wherein said immediate release component and said sustained release component collectively contain a therapeutically effective amount of hydrocodone and a therapeutically effective amount of acetaminophen, wherein said amount of acetaminophen is between about 20 and about 100 times said amount of hydrocodone by weight, wherein the dosage form exhibits a plasma concentration profile for hydrocodone characterized by a first peak concentration (Cmax1) occurring within about 1 to 2 hours after oral administration and a second peak concentration (Cmax2), occurring from about 5 to about 9 hours after oral administration to the human patient.
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93. A sustained release dosage form for twice daily oral dosing to a human patient, comprising
an immediate release component; - and
a sustained release component, wherein said immediate release component and said sustained release component collectively provide a therapeutically effective amount of a nonopioid analgesic and an opioid analgesic, and wherein said immediate release component and said sustained release compoenent provide a means for providing a Cmax for hydrocodone of between about 0.6 ng/mL/mg to about 1.4 ng/mL/mg and a Cmax for acetaminophen of between about 2.8 ng/mL/mg and 7.9 ng/mL/mg after a single dose in the plasma of the patient.
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94. A sustained release dosage form for twice daily oral dosing to a human patient, comprising
an immediate release component; - and
a sustained release component, wherein said immediate release component and said sustained release component collectively provide a therapeutically effective amount of a nonopioid analgesic and an opioid analgesic, and wherein said immediate release component and said sustained release compoenent provide a means for providing an AUC for hydrocodone of between about 9.1 ng*hr/mL/mg to about 19.9 ng*hr/mL/mg and an AUC for acetaminophen of between about 28.6 ng*hr/mL/mg and about 59.1 ng*hr/mL/mg after a single dose.
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95. A method for treating pain in a human patient, comprising orally administering to the human patient on a twice-a-day basis an oral sustained release dosage form comprising:
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(1) a semipermeable wall defining a cavity and including an exit orifice formed or formable therein;
(2) a drug layer comprising a therapeutically effective amount of an opioid analgesic and a nonopioid analgesic contained within the cavity and located adjacent to the exit orifice;
(3) a push displacement layer contained within the cavity and located distal from the exit orifice;
(4) a flow-promoting layer between the inner surface of the semipermeable wall and at least the external surface of the drug layer that is opposite the wall;
wherein the dosage form provides an in vitro rate of release of the opioid analgesic and the nonopioid analgesic for up to about 12 hours after being contacted with water in the environment of use. - View Dependent Claims (96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113)
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- 114. A method for providing an effective amount of an analgesic composition for treating pain in a human patient in need thereof, comprising orally admitting into a patient in need thereof a high load dosage form comprising an effective dose of an opioid analgesic agent and a nonopioid analgesic agent contained in a drug layer and an osmotic push composition, wherein said drug layer and push compositions are surrounded by an at least partially semipermeable wall permeable to the passage of water and impermeable to the passage of said analgesic agents, and an exit means in the wall for delivering the analgesic composition from the dosage form, wherein in operation, water enters through the at least partially semipermeable wall into the dosage form causing the osmotic push composition to expand and push the drug layer through the exit means, wherein the drug layer is exposed to the environment of use as an erodible composition, and wherein the nonopioid analgesic and the opioid analgesic are delivered at a controlled rate over a sustained period of time up to about 12 hours providing a therapeutically effective dose to the patient in need thereof.
- 117. A method for providing an effective concentration of an opioid analgesic and nonopioid analgesic in the plasma of a human patient for the treatment of pain, comprising orally admitting into a patient in need thereof a high load dosage form comprising an effective dose of an opioid analgesic agent and a nonopioid analgesic agent contained in a drug layer, an osmotic displacement composition, wherein said drug layer and displacement compositions are surrounded by an at least partially semipermeable wall permeable to the passage of water and impermeable to the passage of said analgesic agents, and an exit means in the wall for delivering the analgesic composition from the dosage form, wherein in operation, water enters through the at least partially semipermeable wall into the dosage form causing the osmotic displacement composition to expand and push the drug layer through the exit means, wherein the drug layer is exposed to the environment of use as an erodible composition, and wherein the nonopioid analgesic and the opioid analgesic are delivered at a proportional rate over a sustained period of time up to about 12 hours.
Specification