Acetaminophen sustained-release formulation

#This invention relates to sustained-release pharmaceutical formulations, and more particularly to oral acetaminophen sustained-release formulations for providing extended therapeutic relief.

#Many medical conditions are best treated by administration of a pharmaceutical in such a way as to sustain its action over an extended period of time. For example, this kind of pharmaceutical administration can be useful for treating chronic pain, such as that associated with rheumatic or arthritic conditions. Sustained-release dosage forms can also be used beneficially in the administration of antiarrythmics, antihypertensives and other drugs whose sustained action is important to their efficacy.

#Many physiological factors influence both the gastrointestinal transit time and the release of a drug from a controlled release dosage form, and thus influence the uptake of the drug into the systemic circulation. Dosage forms should therefore be designed so that such variable factors do not compromise the efficacy and safety of the product. Ideally, such sustained-release dosage forms should release the active pharmaceutical ingredient at a controlled rate such that the amount of active pharmaceutical ingredient which is available in the body to treat the condition is maintained at a relatively constant level over an extended period of time. That is, it is desirable that active pharmaceutical ingredient be released at a reproducible, predictable rate which is substantially independent of physiological factors which can vary considerably among different individuals and even over time for a particular individual.

#The following examples illustrate preferred combination in immediate-release/ sustained-release acetaminophen formulations in accordance with the invention.

#A preferred combined immediate-release/sustained-release acetaminophen formulation containing 650 milligrams of acetaminophen is set forth in Table 1.

#Tablets are prepared in accordance with the formulations set forth in Table 1 by mixing the micro-crystalline cellulose with sustained-release coated acetaminophen containing acetaminophen, isonunophinal polyoxiethylene glycol ethers, methacrylate ester copolymer and talc in the weight ratio of 20.790; 0.023; 1.531; 1.167. A suitable mixing time for the sustained-release coated acetaminophen particles and the micro-crystalline cellulose is about 1 minute. The mixture of coated acetaminophen and micro-crystalline cellulose are then preferably combined with the cross-linked polyvinylpyrrolidone and with the uncoated acetaminophen. The uncoated acetaminophen (Compap WSE 95%) is comprised primarily of acetaminophen, and contains minor amounts of maltodextrin (a filler) and polyvinylpyrrolidone (povidone). A suitable mixing time for the pre-mixed sustained-release coated acetaminophen and mico-crystalline cellulose, uncoated acetaminophen, and cross-linked polyvinylpyrrolidone is about 10 minutes. Afterward, magnesium sturate is mixed in with the above ingredients. A suitable mixing time for the magnesium stearate with the above ingredients is about 3 minutes.