Pharmaceutical Formulation Containing Opioid Agonist, Opioid Antagonist and Gelling Agent
Disclosed in certain embodiments is an oral dosage form comprising a therapeutically effective amount of an opioid analgesic, an opioid antagonist and one or more pharmaceutically acceptable excipients; the dosage form further including a gelling agent in an effective amount to impart a viscosity unsuitable for administration selected from the group consisting of parenteral and nasal administration to a solubilized mixture formed when the dosage form is crushed and mixed with from about 0.5 to about 10 ml of an aqueous liquid.
1 - 40 . (canceled)
41 . A pharmaceutical dosage form comprising:
a mixture comprising (i) buprenorphine or a pharmaceutically acceptable salt thereof;
(ii) naloxone or a pharmaceutically acceptable salt thereof; and
(iii) a gelling agent comprising polyethylene oxide, the gelling agent in an effective amount to impart a viscosity of at least about 10 cP when the dosage form is subjected to tampering by dissolution in from about 0.5 to about 10 ml of an aqueous liquid;
the dosage form providing an immediate release upon administration to a human patient.
42 . The pharmaceutical dosage form of claim 41 , further comprising buprenorphine hydrochloride.
43 . The pharmaceutical dosage form of claim 41 , further comprising naloxone hydrochloride.
44 . The pharmaceutical dosage form of claim 41 , further comprising hydroxypropylmethylcellulose.
45 . The pharmaceutical dosage form of claim 41 , further comprising a sugar derived alcohol.
46 . The pharmaceutical dosage form of claim 41 , wherein the naloxone or pharmaceutically acceptable salt thereof is in an amount that is parenterally effective
47 . The pharmaceutical dosage form of claim 41 , wherein the gelling agent is in an effective amount to impart a viscosity of at least about 60 cP when the dosage form is subjected to tampering by dissolution in from about 0.5 to about 10 ml of an aqueous liquid.
48 . The pharmaceutical dosage form of claim 41 , wherein the viscosity is measured using a Brookfield Synchro-Lectric Viscometer.
49 . The pharmaceutical dosage form of claim 41 , wherein the ratio of gelling agent to buprenorphine or pharmaceutically acceptable salt thereof is from about 1:40 to about 40:1.
50 . The pharmaceutical dosage form of claim 41 , wherein the aqueous liquid is water.
51 . The pharmaceutical dosage form of claim 41 , wherein the viscosity is imparted when the dosage form is subjected to tampering by dissolution in about 1 to about 3 ml of aqueous liquid.
52 . The pharmaceutical dosage form of claim 41 , wherein the viscosity is obtained when the dosage form is subjected to tampering by dissolution in the aqueous liquid with heating greater than 45° C.
53 . The pharmaceutical dosage form of claim 42 , further comprising naloxone hydrochloride.
54 . The pharmaceutical dosage form of claim 42 , further comprising hydroxypropylmethylcellulose.
55 . The pharmaceutical dosage form of claim 42 , further comprising a sugar derived alcohol.
56 . The pharmaceutical dosage form of claim 42 , wherein the naloxone or pharmaceutically acceptable salt thereof is in an amount that is parenterally effective
57 . The pharmaceutical dosage form of claim 42 , wherein the gelling agent is in an effective amount to impart a viscosity of at least about 60 cP when the dosage form is subjected to tampering by dissolution in from about 0.5 to about 10 ml of an aqueous liquid.
58 . The pharmaceutical dosage form of claim 42 , wherein the viscosity is measured using a Brookfield Synchro-Lectric Viscometer.
59 . The pharmaceutical dosage form of claim 42 , wherein the ratio of gelling agent to buprenorphine or pharmaceutically acceptable salt thereof is from about 1:40 to about 40:1.
60 . The pharmaceutical dosage form of claim 42 , wherein the aqueous liquid is water.
61 . The pharmaceutical dosage form of claim 42 , wherein the viscosity is imparted when the dosage form is subjected to tampering by dissolution in about 1 to about 3 ml of aqueous liquid.
62 . The pharmaceutical dosage form of claim 42 , wherein the viscosity is obtained when the dosage form is subjected to tampering by dissolution in the aqueous liquid with heating greater than 45° C.
63 . The pharmaceutical dosage form of claim 41 , comprising polyethylene oxide having a weight average molecular weight of 50,000 daltons to 1,000,000 daltons.
64 . The pharmaceutical dosage form of claim 41 , comprising polyethylene oxide having a weight average molecular weight of 100,000 daltons.
65 . The pharmaceutical dosage form of claim 41 , comprising polyethylene oxide having a weight average molecular weight of 200,000 daltons.
66 . The pharmaceutical dosage form of claim 41 , comprising polyethylene oxide having a weight average molecular weight of 50,000 daltons to 1,000,000 daltons.
67 . The pharmaceutical dosage form of claim 41 , comprising polyethylene oxide having a weight average molecular weight of 100,000 daltons.
68 . The pharmaceutical dosage form of claim 41 , comprising polyethylene oxide having a weight average molecular weight of 200,000 daltons.
69 . A pharmaceutical dosage form comprising:
a mixture comprising (i) buprenorphine or a pharmaceutically acceptable salt thereof;
(ii) naloxone or a pharmaceutically acceptable salt thereof; and
(iii) a gelling agent comprising polyethylene oxide, hydroxypropylmethylcellulose and sugar derived alcohol; the gelling agent in an effective amount to impart a viscosity of at least about 10 cP when the dosage form is subjected to tampering by dissolution in from about 0.5 to about 10 ml of an aqueous liquid;
the dosage form providing an immediate release upon administration to a human patient.
70 . A pharmaceutical dosage form comprising:
a mixture comprising (i) buprenorphine hydrochloride;
(ii) naloxone hydrochloride; and
(iii) a gelling agent comprising polyethylene oxide, hydroxypropylmethylcellulose and sugar derived alcohol; the gelling agent in an effective amount to impart a viscosity of at least about 10 cP when the dosage form is subjected to tampering by dissolution in from about 0.5 to about 10 ml of an aqueous liquid;
the dosage form providing an immediate release upon administration to a human patient.