Study On Indomethacin Transdermal Patch

Indomethacin is a non-steroidal anti-inflammatory drug,which has excellent anti-inflammatory,analgesic and antipyretic efficacy.It is widely used for the treatment of rheumatic arthritis and rheumatoid arthritis in clinics.But it may bring up adverse effects on gastrointestinal tract when orally administrated.Even bleeding and ulceration often occur. There are several kinds of dosage forms marketed such as tablet,injection and topical gel.In order to avoid its adverse effect by oral administration and be administrated conveniently,the topical patch of indomethacin was formulated and studied.Differential scanning calorimetry was used to evaluate the compatibility between indomethacin and MASCOS 10（polyacrylic acid type）pressure sensitive adhesive.The experimental results showed that drug and excipients were stable and they were compatible with each other.To determine the formulation composition of a transdermal drug delivery system of indomethacin,the method of evaporating organic solvent was established to prepare indomethacin patch with MASCOS 10 as a vehicle.The enhancing effects of the permeation enhancers（i.e.azone,menthol,isopropyl myristate（IPM）,tween-80 and oleic acid）were evaluated using two-chamber side-by-side diffusion cells containing excised rat skin to screen the permeation enhancers in order to improve the drug permeation.It was notable that the presence of IPM,oleic acid and tween-80 did not increase indomethacin permeation from the transdermal patches compared with the transdermal patches containing azone and menthol （P＞0.05）.5%azone and 5%menthol were the permeation enhancers of choice for the percutaneous absorption of indomethacin.The adhesion of patches was demonstrated by adhesion experiment.Tack,shear strength and peel strength were measured to estimate the adhesion of the patch because the adhesive is critical for the safety,efficacy and quality of the product.The drug content and drug release rate of the patch are also essential standards in industrial process,so the work was complicated.The stability experiments showed that indomethacin patches were stable.A simple reversed-phase HPLC method has been developed for determination of indomethacin in rat plasma,excised skin and muscles samples.As compared to oral administration without dose normalization,the Cmax values of transdermal administration were significantly decreased（1.92μg/ml for transdermal administration versus 3.84μg/ml for oral administration）.On the contrary,the[AUC]_0-48hvalues were significantly increased（47.99μg·h/ml for transdermal administration versus 31.38μg·h/ml for oral administration）,and the MRT values evidently extended（16.65 h for transdermal administration versus 7.74 h for oral administration）.The transdermal patches incorporating indomethacin would provide a useful strategy for prevention and treatment of inflammation,suggesting that the possible side effects from indomethacin may be attenuated due to the lowered peak concentrations,and pharmacological effects can be enhanced and extended.