Acetaminophen has been safely used for analgesia for many years.
Literature suggests that a plasma acetaminophen level of 5��g/ml is necessary to
maintain analgesic relief in humans. Current dosing regiments are inconvenient (every
4-6 hours) and do not maintain this minimum plasma level. Simulations were
conducted to examine various doses and input rates for sustained release formulations
of acetaminophen. Once parameters were selected from the simulations, sample
formulations were prepared and tested using standard dissolution techniques.
Investigations into dose/size relationships, hydroxypropylmethylcellulose (HPMC)
percentage for erosion matrix tablets, compression force, tablet shape, tablet
divisibility, and granulation methods were performed for non-disintegrating
hydrophilic matrix tablets.
Tablets containing 5% and 7.5% HPMC were selected for pharmacokinetic
study in 10 healthy human subjects. Tylenol Extra Strength and Tylenol Extended
Relief tablets were administered as control formulations. Pharmacokinetic fitting of
the kinetic profiles of all four formulations were performed using Win Nonlin. The
formulations were best described by a 1-compartment open model with first order
input and first order elimination. The 5% HPMC sustained release acetaminophen
formulation was selected for Phase II clinical trials.
Patients with osteoarthritis of the knee were recruited for a double blind
crossover study of 5% HPMC sustained release acetaminophen formulations and
immediate release acetaminophen. Patients received two tablets of study medication,
four times a day for 4 weeks. After a seven day wash-out period patients were then
crossed over to the other treatment. Patients were evaluated using a twelve question
questionnaire and the time to walk 50 feet was measured. Thirty patients were
enrolled in the study and seventeen patients completed the study. The sustained
release formulations were statistically superior to the baseline treatments in reducing
pain level, decreasing disability, and improving the duration of pain relief. Additional,
larger scale studies are needed to confirm these findings. / Graduation date: 2000
| Identifer | oai:union.ndltd.org:ORGSU/oai:ir.library.oregonstate.edu:1957/33246 |
| Date | 04 May 2000 |
| Creators | Keller, Carol Ann |
| Contributors | Ayres, James W. |
| Source Sets | Oregon State University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
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