DEVELOPMENT OF A NEW CONTROLLED RELEASE DOSAGE FORM OF ACETYLSALICYLIC ACID

The pharmaceutical agent, acetylsalicylic acid (ASA) is commonly used in the treatment of rheumatoid arthritis. However, due to the gastrointestinal injury caused by the ASA, it is recommended that patients who must take ASA regularly, use enteric coated ASA. Additionally, the short half-life of ASA requires that the drug be administered FOUR times daily in order to maintain therapeutic plasma levels in the arthritic patient. These two properties render ASA a good candidate for reformulation into both an enteric-coated and controlled release dosage form. Acetylsalicylic acid granules were microencapsulated in the laboratory, using Eudragit L30D (an aqueous based enteric coating resin) and a fluidized bed coating apparatus. Portions of the microencapsulated granules were compressed into tablets. Both the ASA tablets and granules were compared with commercially available ASA products (Entrophen 10, {Frosst}; and Bayer Sustained Release Aspirin, {Bayer}), in vitro, (dissolution rate testing). Differences in dissolution rate constants and dissolution half-lives (Two) were analyzed by one-way analysis of variance for the effect of formulation (six groups of ASA dosage forms were tested) and the effect of the method of dissolution rate analysis (U.S.P. basket versus paddle apparatus). The differences between pairs of means were subsequently evaluated using the Student Newman-Keuls test. Also, the effect of pH (of the dissolution media) and the effect of particle size (of the granules being tested) were determined. The dissolution rate of ASA from the Eudragit tablets increased with an increase in pH (pH range 1.2 - 7.5). The particle size of the enteric coated ASA granules also had a significant effect on the dissolution rate, whereby an increase in particle size resulted in a decrease in dissolution rate. Inter-batch consistency (of tablets compressed from Eudragit coated granules) was remarkable, with no significant difference occurring among the mean dissolution half-lives of the lots tested. The remaining formulations, (Bayer Sustained Release, Entrophen 10 and uncoated 60 mesh ASA granules) were all significantly different from each other and from the Eudragit coated tablets. The mean dissolution Tmc, of the Bayer Sustained Release tablet (34.77 minutes) was significantly shorter than the Tmc, for the Eudragit coated tablets, (mean dissolution Tmc, 123.36 minutes).

Name thesis:degree_name

Master of Science (M.Sc.)

Level thesis:degree_level

Masters

Grantor

University of Saskatchewan

Year dc:date.issued

1985

Author dc:creator

• Sutherland, Hugh Warren

• acetylsalicylic acid

Handle dc:identifier.uri

https://hdl.handle.net/10388/15371

OAI identifier oai:identifier

oai:harvest.usask.ca:10388/15371