Preparation Of Ketoprofen 24-Hour-Sustained-Release Tablets And Optimization Of Formulation And Process

Ketoprofen is one of non-steroidal anti-inflammatory drugs, which contains phenylpropionic acid in structure. It has a clear anti-inflammatory, analgesic and antipyretic effect and frequently used for rheumatoid arthritis, rheumatic arthritis, osteoarthritis, ankylosing spondylitis, acute gout, but common oral dosage forms of ketoprofen has shortcomings of short biological half-life(1.6-1.9 h) and blood drug level decreased in short time so that patients need frequent administration(t.i.d or q.i.d).Ketoprofen stimulates gastrointestinal tract and patients suffer digestive ulcer or gastrointestinal hemorrhage if treated for a long time.At present, most of domestic preparations of ketoprofen are common tablets or enteric-coated capsules that need to be administered several times a day, which affects therapeutic effect and medication safety. Therefore it's necessary to study on ketoprofen sustained-release preparations.Based on the domestic research of pharmaceutical materials used for sustained-release and controlled-release preparations, hydroxypropyl methylcellulose (HPMC) of different viscosities mixed in certain proportion were chosen as major matrix material and lactose as bulking agent, and ketoprofen matrix tablets which can continuously release drug for 24 hours were prepared. First of all, the matrix material, bulking agent, lubricant, glidant and procedure of preparation were screened, and in the next various factors in formulation including amount of HPMC and lactose, particle size of ketoprofen and concentration of adhesive which affect the release of drug were studied by determinate drug release in vitro in buffer(pH 7.2). The results indicated that HPMC decreased the drug release and lactose promoted it. The tableting method, the size of tablets and the tableting pressure were studied furthermore and the tableting method had significantly effects on the drug release. The formulation and procedure optimized according to the results were verified by prepared 3 batches of tablets consecutively. The drug release was good and stable as expected. Finally, the mechanism of release of ketoprofen in the sustained-release tablets was studied by fitting the drug release data to zero-order, first-order, Higuchi and Ritger-Peppas equation.The results showed that the drug release pattern from the matrix tablets was approach to first-order eqution, and was interaction of diffusion and corrosion which belonged to the irregular transport.Common ways of developing 24-hour-sustained-release preparations were discussed in this topic, which provided ideas and methods for the design and screening of sustained-release preparations in the future.