International Journal of Pharmaceutics, 77 (1991) 177-181 0 1991 Elsevier Science Publishers B.V. All rights reserved 0378-5173/91/$03.50 177 IJP 02567 Ketoprofen pulsatile absorption from ‘multiple unit’ hydrophilic matrices P. Giunchedi, L. Maggi, U. Conte and C. Caramella Department of Pharmaceutical Chemistry, Unicersity of Palia, Via Taramelli 12, 27100 Pavia (Italy) (Received 16 May 1991) (Accepted 5 July 1991) Key words: Ketoprofen; NSAID; Hydrophilic matrix; Multiple-unit formulation; Drug release, in vitro constant; Plasma level, pulsatile Summary Ketoprofen is an analgesic and non-steroidal anti-inflammatory drug (NSAIDJ usually employed in the therapy of rheumatic disorders, and is rapidly eliminated from the blood after dosing (plasma half-life l-3 h). Therefore, extended release dosage forms of this drug may be beneficial, but constant drug release is not always the optimal choice for its administration, since, owing to circadian rhythms, some pathologies (such as rheumatoid disorders) may require different, consecutive pulses of drug. In this work, an extended-release oral formulation of ketoprofen was prepared. It is a ‘multiple-unit’ formulation constituted by four hydrophilic matrices of identical composition, prepared with hydroxypropylmethylcellulose (Methocel”) and placed in a gelatin capsule. Each unit contains 50 mg of drug. In vivo tests carried out on 12 healthy volunteers demonstrated that pulsatile plasma levels (two peaks at second and eighth hours after dosing) correspond to an in vitro fairly constant drug release. In vitro and in vivo test results were also compared with those obtained from a commercial ketoprofen oral modified release formulation (capsule containing pellets). Introduction Ketoprofen (2-arylpropionic acid derivative) is an important analgesic and non-steroidal anti-in- flammatory drug, also with antipyretic properties, whose mechanism of action is the inhibition of prostaglandin synthetase (Avouac et al., 1988). This drug is used in the therapy of rheumatic disorders, such as rheumatoid arthritis, os- teoarthritis and ankylosing spondylitis, and is also Correspondence: U. Conte, Dept of Pharmaceutical Chem- istry, University of Pavia, Via Taramelli 12, 27100 Pavia, Italy. used to relieve pains of non-rheumatoid origin (Avouac et al., 1988). Its usual dose is from 50 to 100 mg twice daily, orally (Martindale, 19891, and among anti- rheumatic agents it is one of the most well toler- ated. Like other non-steroidal anti-inflammatory agents (such as ibuprofen, diclofenac and in- domethacin), ketoprofen is rapidly eliminated from the blood after dosing (Houghton et al., 1984), its plasma elimination half-life being l-3 h (Jamali and Brocks, 19901, and in order to main- tain therapeutic plasma levels the drug must be administered at least twice daily.