TAMPER RESISTANT DOSAGE FORMS
The present invention relates to pharmaceutical dosage forms, for example to a tamper resistant dosage form including an opioid analgesic, and processes of manufacture, uses, and methods of treatment thereof.
1 - 169 . (canceled)
170 . A method of treating pain comprising administering to a patient in need thereof a cured shaped extended release tablet comprising:
(1) an opioid or a pharmaceutically acceptable salt thereof,
(2) at least one low molecular weight polyethylene oxide having, based on rheological measurements, an approximate molecular weight of less than 1,000,000, and
(3) at least one high molecular weight polyethylene oxide having, based on rheological measurements, an approximate molecular weight of 7,000,000;
wherein said tablet is prepared by a process comprising the steps of:
(a) providing a first combination comprising said high molecular weight polyethylene oxide and said opioid or pharmaceutically acceptable salt thereof; and
(b) providing a second combination comprising said low molecular weight polyethylene oxide and optionally comprising said opioid or pharmaceutically acceptable salt thereof; and
(c) forming a shaped tablet comprising the first and second combinations;
(d) curing said shaped tablet by applying an air temperature from about 60° C. to about 90° C. for a time of from about 15 minutes to about 10 hours; and
(e) optionally applying one or more coatings to said shaped tablet;
wherein the total combined weight of said high and low molecular weight polyethylene oxides is at least 79% by weight, and said percent by weight is based upon the total weight of said shaped tablet, not including the combined weight of said coatings.
171 . A method of treating pain as defined in claim 170 , wherein the percent by weight of said opioid or pharmaceutically acceptable salt is at least 2.4%, based on the total weight of said uncoated tablet.
172 . A method of treating pain as defined in claim 170 , wherein said time in said curing step is 15 minutes to 90 minutes.
173 . A method of treating pain as defined in claim 170 , wherein said air temperature in said curing step is from about 70° C. to about 78° C.
174 . A method of treating pain as defined in claim 170 , wherein
said coating, when present, is applied at least one of before or after said curing step and said coating comprises a film coating, microcrystalline cellulose, hydroxypropyl cellulose, magnesium stearate, talc, silica, fumed silica, colloidal silica dioxide, calcium stearate, carnauba wax, stearic acid, stearyl alcohol, mineral oil, paraffin, glycerin, propylene glycol, polyethylene glycol, lactose, povidone, or combinations thereof, and
said additive, when present, comprises microcrystalline cellulose, hydroxypropyl cellulose, magnesium stearate, talc, silica, fumed silica, colloidal silica dioxide, calcium stearate, carnauba wax, stearic acid, stearyl alcohol, mineral oil, paraffin, glycerin, propylene glycol, polyethylene glycol, lactose, povidone, or combinations thereof.
175 . A method of treating pain comprising administering to a patient in need thereof a cured shaped extended release tablet comprising:
(1) hydrocodone or a pharmaceutically acceptable salt thereof,
(2) at least one low molecular weight polyethylene oxide having, based on rheological measurements, an approximate molecular weight of less than 1,000,000, and
(3) at least one high molecular weight polyethylene oxide having, based on rheological measurements, an approximate molecular weight of 7,000,000;
wherein said tablet is prepared by a process comprising the steps of:
(a) providing a first combination comprising said high molecular weight polyethylene oxide and said opioid or pharmaceutically acceptable salt thereof; and
(b) providing a second combination comprising said low molecular weight polyethylene oxide and optionally comprising said opioid or pharmaceutically acceptable salt thereof; and
(c) forming a shaped tablet comprising the first and second combinations;
(d) curing said shaped tablet by applying an air temperature from about 60° C. to about 90° C. for a time of from about 15 minutes to about 10 hours; and
(e) optionally applying one or more coatings to said shaped tablet;
wherein said low molecular weight polyethylene oxide is at least 20% by weight, and the total combined weight of said high and low molecular weight polyethylene oxides is at least 79% by weight, and said percent by weight is based upon the total weight of said shaped tablet, not including the combined weight of said coatings.
176 . A method of treating pain as defined in claim 175 , wherein, said temperature in said curing step is from about 70° C. to about 78° C.
177 . A method of treating pain as defined in claim 175 , wherein
said coating, when present, is applied at least one of before or after said curing step and said coating comprises a film coating, microcrystalline cellulose, hydroxypropyl cellulose, magnesium stearate, talc, silica, fumed silica, colloidal silica dioxide, calcium stearate, carnauba wax, stearic acid, stearyl alcohol, mineral oil, paraffin, glycerin, propylene glycol, polyethylene glycol, lactose, povidone, or combinations thereof, and
said additive, when present, comprises microcrystalline cellulose, hydroxypropyl cellulose, magnesium stearate, talc, silica, fumed silica, colloidal silica dioxide, calcium stearate, carnauba wax, stearic acid, stearyl alcohol, mineral oil, paraffin, glycerin, propylene glycol, polyethylene glycol, lactose, povidone, or combinations thereof.
178 . A method of treating pain as defined in claim 175 , wherein the percent by weight of said low molecular weight polyethylene oxide is at least 29% and the percent by weight of said high molecular weight polyethylene oxide is at least 50%, based upon the total weight of said uncoated tablet.
179 . A method of treating pain as defined in claim 175 , wherein said tablet comprises at least one coating, and wherein the percent by weight of said hydrocodone or pharmaceutically acceptable salt thereof is at least 2.4%, based upon the total weight of said uncoated tablet.
180 . A method of treating pain as defined in claim 175 , wherein said tablet comprises at least one coating, and wherein the percent by weight of said hydrocodone or pharmaceutically acceptable salt thereof is at least 5%, based upon the total weight of said uncoated tablet.
181 . A method of treating pain as defined in claim 175 , wherein said tablet comprises at least one coating, and wherein the percent by weight of said hydrocodone or pharmaceutically acceptable salt thereof is at least 10%, based upon the total weight of said uncoated tablet.
182 . A method of treating pain as defined in claim 178 , wherein the total combined weight of said high and low molecular weight polyethylene oxides is at least 80% by weight, based upon the total weight of said uncoated tablet.
183 . A method of treating pain as defined in claim 179 , wherein, said air temperature in said curing step is from about 70° C. to about 78° C.
184 . A method of treating pain as defined in claim 175 , wherein said time in said curing step is 15 minutes to 90 minutes.
185 . A method of treating pain as defined in claim 179 , wherein said coating, when present, is applied at least one of before or after said curing step and said coating comprises a film coating, microcrystalline cellulose, hydroxypropyl cellulose, magnesium stearate, talc, silica, fumed silica, colloidal silica dioxide, calcium stearate, carnauba wax, stearic acid, stearyl alcohol, mineral oil, paraffin, glycerin, propylene glycol, polyethylene glycol, lactose, povidone, or combinations thereof, and
said additive, when present, comprises microcrystalline cellulose, hydroxypropyl cellulose, magnesium stearate, talc, silica, fumed silica, colloidal silica dioxide, calcium stearate, carnauba wax, stearic acid, stearyl alcohol, mineral oil, paraffin, glycerin, propylene glycol, polyethylene glycol, lactose, povidone, or combinations thereof.
186 . A method of treating pain as defined in claim 179 , wherein said temperature in said curing step is from about 70° C. to about 78° C. and said time in said curing step is 15 minutes to 90 minutes.
187 . A method of treating pain as defined in claim 180 , wherein said temperature in said curing step is from about 70° C. to about 78° C. and said time in said curing step is 15 minutes to 90 minutes.
188 . A method according to claim 179 , wherein the percent by weight of said high molecular weight polyethylene oxide is at least 54%, based upon the total weight of said uncoated tablet.
189 . A method of treating pain as defined in claim 175 , wherein the total combined weight of said high and low molecular weight polyethylene oxides is at least 85% by weight, based upon the total weight of said uncoated tablet.
190 . A method of treating pain as defined in claim 179 , wherein the total combined weight of said high and low molecular weight polyethylene oxides is at least 90% by weight, based upon the total weight of said uncoated tablet.
191 . A method according to claim 179 , wherein the total combined weight of said high and low molecular weight polyethylene oxides is at least 80% by weight, based upon the total weight of said uncoated tablet, and
said shaped tablet comprises at least one of a coating, an additive, and combinations thereof, wherein
said coating, when present, is applied at least one of before or after said curing step and said coating comprises a film coating, microcrystalline cellulose, hydroxypropyl cellulose, magnesium stearate, or combinations thereof, and
said additive, when present, comprises microcrystalline cellulose, hydroxypropyl cellulose, magnesium stearate, or combinations thereof.
192 . A method of treating pain as defined in claim 179 , wherein the total combined weight of said high and low molecular weight polyethylene oxides is at least 85% by weight, based upon the total weight of said uncoated tablet.
193 . A method of treating pain as defined in claim 179 , wherein the total combined weight of said high and low molecular weight polyethylene oxides is at least 90% by weight, based upon the total weight of said uncoated tablet.
194 . A method of treating pain as defined in claim 191 , wherein said cured shaped tablet comprises an additive selected from microcrystalline cellulose, hydroxypropyl cellulose, magnesium stearate, and combinations thereof.
195 . A method of treating pain as defined in claim 194 , wherein said curing comprises convection curing in a convection curing device.
196 . A method of treating pain as defined in claim 179 , wherein said curing comprises convection curing in a convection curing device and said air temperature is measured as a mean exhaust temperature of said convection curing device during said curing duration.
197 . A method of treating pain as defined in claim 195 , wherein said air temperature is measured as a mean exhaust temperature of said convection curing device during said curing duration.
198 . A method of treating pain as defined in claim 175 , wherein said cured shaped tablet, when measured without said optional coating, has a density that is at least about 1% lower than the density of said shaped tablet prior to curing, based upon an uncoated tablet.
199 . A method according to claim 195 , wherein said cured shaped tablet has a density that is at least about 1% lower than the density of said shaped tablet prior to curing.