TAMPER RESISTANT DOSAGE FORMS

1 - 169 . (canceled)

170 . A solid, oral, extended release pharmaceutical tablet comprising:

(A) a core comprising:

a therapeutically effective amount of a hydrochloride salt of an opioid analgesic;

an antioxidant;

hydroxypropyl methylcellulose;

polyethylene glycol;

at least one hardened high molecular weight polyethylene oxide (PEO), wherein said high molecular weight PEO has an approximate molecular weight of from 4 million to 8 million, based upon rheological measurements, and is present in an amount of at least about 30% (by weight) of the core;

(B) a coating on said core, said coating comprising:

a. polyethylene glycol;

b. talc; and

c. titanium dioxide;

wherein said tablet

is crush resistant and has a breaking strength of at least about 439 N;

is resistant to alcohol extraction and has an in vitro dissolution rate of said opioid hydrochloride salt, at 0.5 hours in simulated gastric fluid with 40% ethanol, that differs by no more than about 20% points from a corresponding in vitro dissolution rate without ethanol; and

provides a mean t max of said opioid hydrochloride salt at about 2 to about 6 hours after administration of a single tablet in a human subject.

171 . A tablet according to claim 170 , wherein the opioid hydrochloride salt comprises at least about 1.3% (by weight) of the core.

172 . A tablet according to claim 171 , wherein the opioid hydrochloride salt comprises at least about 2.4% (by weight) of the core.

173 . A tablet according to claim 171 , wherein the opioid hydrochloride salt comprises at least about 5% (by weight) of the core.

174 . A tablet according to claim 170 , wherein

after storage at 40° C., 75% relative humidity in a closed 100 count bottle for 3 months, said tablet releases at least 95% of the amount of opioid hydrochloride salt in said tablet before such storage, as determined by stirring and dissolution in a medium comprising simulated gastric fluid for 12 hours; and

after storage at 25° C., 60% relative humidity in a closed 100 count bottle for 6 months, releases at least 95% of the amount of opioid hydrochloride salt in said tablet before such storage, as determined by stirring and dissolution in a medium comprising simulated gastric fluid for 12 hours.

175 . A tablet according to claim 170 , wherein

(i) when said tablet is flattened without breaking to no more than about 60% of its thickness before flattening, said flattened tablet has an in-vitro dissolution, when measured in a USP Apparatus 1 (basket) at 100 rpm and at 37° C. in 900 ml of simulated gastric fluid having no enzymes and having 40% ethanol, wherein the percent amount of said opioid hydrochloride salt released at 0.5 hours of dissolution deviates no more than about 15% from the corresponding in-vitro dissolution without ethanol;

(ii) between 5 and 40% of said opioid hydrochloride salt (by weight) in said tablet is released after 0.5 hours, when measured in a USP Apparatus 1 (basket) at 100 rpm and at 37° C. in 900 ml of simulated gastric fluid having no enzymes and having 40% or 0% ethanol; or

(iii) a combination of (i) and (ii).

176 . A tablet according to claim 170 , wherein the molecular weight of said high molecular weight PEO is at least one of 4 million, 5 million, 7 million, and 8 million.

177 . A tablet according to claim 170 , wherein the molecular weight of said high molecular weight PEO is at least one of 4 million and 7 million.

178 . A tablet according to claim 170 , wherein said high molecular weight PEO comprises at least about 50% (by weight) of said core.

179 . A tablet according to claim 178 , wherein said high molecular weight PEO comprises at least about 65% (by weight) of the core.

180 . A tablet according to claim 179 , wherein said high molecular weight PEO comprises at least about 80% (by weight) of the core.

181 . A tablet according to claim 180 , wherein said high molecular weight PEO comprises at least about 90% (by weight) of the core.

182 . A tablet according to claim 178 , wherein the antioxidant is Vitamin E and the molecular weight of said high molecular weight PEO is at least one of 4 million and 7 million.

183 . A tablet according to claim 179 , wherein the antioxidant is Vitamin E and the molecular weight of said high molecular weight PEO is at least one of 4 million and 7 million.

184 . A tablet according to claim 180 , wherein the antioxidant is Vitamin E and the molecular weight of said high molecular weight PEO is at least one of 4 million and 7 million.

185 . A tablet according to claim 181 , wherein the antioxidant is Vitamin E and the molecular weight of said high molecular weight PEO is at least one of 4 million and 7 million.

186 . A tablet according to claim 174 , wherein the opioid hydrochloride salt comprises at least about 5% (by weight) of said core and said high molecular weight PEO comprises at least about 50% (by weight) of said core.

187 . A tablet according to claim 175 , wherein the opioid hydrochloride salt comprises at least about 5% (by weight) of said core and said high molecular weight PEO comprises at least about 50% (by weight) of said core.

188 . A tablet according to claim 186 , wherein the molecular weight of said high molecular weight PEO is at least one of 4 million and 7 million.

189 . A tablet according to claim 188 , wherein the molecular weight of said high molecular weight PEO is at least one of 4 million and 7 million.

190 . A tablet according to claim 170 , wherein the opioid hydrochloride salt comprises at least about 5% (by weight) of said core, the dosage amount of opioid hydrochloride salt is about 5 mg to about 500 mg, the antioxidant is Vitamin E, and the molecular weight of said high molecular weight PEO is at least one of 4 million and 7 million.

191 . A tablet according to claim 174 , wherein the opioid hydrochloride salt comprises at least about 5% (by weight) of said core, the dosage amount of opioid hydrochloride salt is about 5 mg to about 500 mg, the antioxidant is Vitamin E, and the molecular weight of said high molecular weight PEO is at least one of 4 million and 7 million.

192 . A tablet according to claim 175 , wherein the opioid hydrochloride salt comprises at least about 5% (by weight) of said core, the dosage amount of opioid hydrochloride salt is about 5 mg to about 500 mg, the antioxidant is Vitamin E, and the molecular weight of said high molecular weight PEO is at least one of 4 million and 7 million.

193 . A tablet according to claim 178 , wherein the dosage amount of opioid hydrochloride salt is about 5 mg to about 500 mg.

194 . A tablet according to claim 193 that is suitable for twice-daily administration to a human patient in need of analgesic treatment.

195 . A solid, oral, extended release pharmaceutical tablet comprising:

(A) a core consisting of:

a. a therapeutically effective amount of a hydrochloride salt of an opioid analgesic;

b. vitamin E;

c. hydroxypropyl methylcellulose;

d. polyethylene glycol;

e. at least one high molecular weight polyethylene oxide (PEO) that is hardened by exposure to a temperature of at least 60° C., wherein said high molecular weight PEO

has an approximate molecular weight of from 4 million to 8 million, based upon rheological measurements, and is present in an amount of at least about 30% (by weight) of the core;

(B) a coating on said core, said coating comprising:

a. polyethylene glycol;

b. talc; and

c. titanium dioxide;

wherein said tablet

is crush resistant and has a breaking strength of at least about 439 N;

is resistant to alcohol extraction and has an in vitro dissolution rate of said opioid hydrochloride salt, at 0.5 hours in simulated gastric fluid with 40% ethanol, that differs by no more than about 20% points from a corresponding in vitro dissolution rate without ethanol; and

provides a mean t max of said opioid hydrochloride salt at about 2 to about 6 hours after administration of a single tablet in a human subject.

196 . A tablet according to claim 195 , wherein the molecular weight of said high molecular weight PEO is at least one of 4 million and 7 million.

197 . A tablet according to claim 196 , wherein the opioid hydrochloride salt comprises at least about 5% (by weight) of the core.

198 . A tablet according to claim 197 , wherein said high molecular weight PEO comprises at least about 50% (by weight) of said core.

199 . A tablet according to claim 197 , wherein the dosage amount of opioid hydrochloride salt is about 5 mg to about 500 mg, and the tablet is suitable for twice-daily administration to a human patient in need of analgesic treatment.