LAUSR

Abstract The aim of this research is to develop sustained release Tenoxicam (TNX) in situ forming microparticles to substitute the conventional oral dosage forms for the treatment of rheumatoid arthritis (RA). This new formulation is anticipated to enhance anti-arthritis efficacy, reduce acute toxicity and achieve patient compliance. A factorial design was adopted to evaluate the impact of two variables, namely, Poly (DL-lactide) (PDL 02) concentration at three levels (20%, 30% and 40%) and PDL 02 phase: sesame oil (SO) phase ratio at four levels (1:0, 1:1, 1:2 and 1:4). The effect of these factors on the TNX burst release and release rate was studied. Two in situ forming systems were prepared, namely, an in situ implant (ISI) composed of the polymer system and in situ microparticles (IMP) based on the polymer/oil system. All formulations were fully characterized, and a comparative in vivo/in vitro release study and a histopathological study were carried out. Anti-arthritis efficacy and acute toxicity of the optimized TNX in situ microparticles (IMP5) compared to those of oral TNX were measured using Freund's Complete Adjuvant (FCA) induced arthritis model in rats. IMP (6.77%) reduced the burst release of the drug compared to ISI (30.51%). The histopathological study endorsed the potential use of IMP for its higher protection against the inflammatory responses compared to ISI. This protective effect may be attributed to the synergistic effect of the anti-inflammatory and antioxidative effects of both SO and TNX. The in vivo study showed that IMP5 significantly reduced (p