The Study Of Oxaprozin On Penetation Across The Mouse Skin And Gels

Oxaprozin (Oxap) is a novel non-steroidal anti-inflammatory drug belonging to the propionic acid analogue which is used in the management of gouty arthritis, ankylosing spondylitis, osteoaarthritis, rheumatoid arthritis, tendonitis, bursitis and Behcet?s disease. The dosage forms of oxaprozin authorized on the market in China are only tablet and enteric capsule. Like other non-steroidal anti-inflammatory drugs, mild gastrointestinal complaints (e.g. nausea, diarrhoea, constipation, gastralgia and occasionally vomiting) are the most frequently occurring side effects of oxaprozin, rarely with serious gastric ulcer, along with mild central nervous system effects (e.g. headache, vertigo). The transdermal administration of oxaprozin is a new approach which is beneficial for the treatment of rheumatic, locally pain and inflammatory, avoiding the side-3-ABSTRACTeffects of oral administration. Definitely, the transderinal administration of oxaprozin will give full play to its clinical effects.In this thesis, some physicochemical properties were determined and the transdermal delivery across mouse skin of oxaprozin was studied by using Valia-Chien diffusion cell. In the first place, the effects of pH on the penetration of oxaprozin were studied. It was shown that the steady-state flux (J~) of oxaprozin was increasing with the augment of pH and the permeability coefficient (Ps) of oxaprozin was decreasing with the increase of pH, but the accumulative penetration amount (Q) was increasing with the augment of pH. It is possible to increase the accumulative penetration amount of drugs by adjusting the value of pH. The feasible pH for the transdermal absorption was ensured according to the result of experiment.The transdermal delivery across rat skin of oxaprozin with three widely used enhancers and the best concentration of Azone were studied. It was shown that the permeation kinetics of oxaprozin across the mouse skin was zero-order and the enhancing effect of Azone on oxaprozin is dependent on its concentration. Among 1%Azone, 3%Azone, 5%Azone and 1O%Azone, 3%Azone is the best one. According to the experiment, oxaprozin can penetrate across the rat skin, however, the values of the steady-state flux (J~) and permeability coefficient (Ps) of oxaprozin are relatively very small which are 1.717 X iO~ i~ g/cm2s and 1.308 X 1 06cm/s respectively. The application of enhancers could increase the permeability of the drug with the enhancement ratio> 1. According to the t-test, J~ of oxaprozin with the treatment of 3%Azone and 10%OA was significantly increased to 11.013 X i0~ ~i g/cm2s and 5.428 X i03 i-i-4-ABSTRACTg/cm2s, respectively(P