Ketoprofen pulsatile absorption from ‘multiple unit’ hydrophilic matrices

Abstract

Abstract Ketoprofen is an analgesic and non-steroidal anti-inflammatory drug (NSAID) usually employed in the therapy of rheumatic disorders, and is rapidly eliminated from the blood after dosing (plasma half-life 1–3 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).