Study On Ketoprofen Orally Delayed Release System

The present project was aimed to preparing a novel drug delivery system which could automatically release a desired amount of drug after the predetermined lag time. Ketoprofen has been mainly used for rheumatoid arthritis in clinical therapeutics. The objective of the study was to prepare and evaluate a delayed release tablets and pellets by film coating technique , using ketoprofen as model drug , which attempts to address clinically therapeutic requirements.In this study , UV spectrophotometry was developed for in vitro assay during the study of release , content and physico-chemical properties of ketoprofen . The studies on solubility showed that the equilibrium solubility in distilled water , pH6.8 phosphate buffer were 0.2mg/mL and 5.7mg/mL . Cast free films of ethylcellulose with different composition were prepared . The tensile strength , elastic modulus and permeability of free films were calculated to investigate the properties of preparation which was coated with the same film composition .The ketoprofen delayed release tablets was prepared and was designed to be administered at night and release its drug in the next early morning . Carboxymethyl starch sodium(CMS-Na) was selected as swelling material to make the tablet core. Ethylcellulose (EC) was used as the outer coating material which was insoluble in water and pH-independent . Triethyl citrate (TEC) was employed as the plasticizer . We investigated the effect of the composition and thickness of the coating film on drug release . The coating formulation was optimized by central composite design (CCD) , having the lag time (T10%) and the delayed release rate (T10-90%) as the evaluation standard . The result showed that the dosage of EC and TEC were both important factors to T10% . When the level of EC is 5% and TEC is 15% of EC respectively , T10%=5.6h , T10-90%=0.72h.A laboratory scale bottom spray fluid bed was designed and applied to the drug layering and film coating of ketoprofen delayed release pellets . The most significantprocess variables and other relevant quality standards were studied . The results showed that the equipment was quite suitable for drug layering and film coating . The timed release pellets consist of 5 laminar layers from the center to the outside :the core, the drug layer, the swelling agent layer , the block layer and the controlled layer . The factors which affect the lag time and drug release behavior were investigated, such as the thickness of the inner and outer layers, the amount of the plasticizer and pore-former, etc.. The results showed that the swelling layer played an important role in the formulation since the drug release is triggered by the destruction of the outer membrane. The lag time was prolonged in some degree with the increase of the outer layer or the block layer or the amount of plasticizer . And increase the amout of pore-former would speed the drug release after T|0<>/0. Eventually , the optimized pellets was prepared with Tio%=4-5h .The result of stability test showed that the delayed release tablets and pellets were unstable under high humidity condition , and were stable when exposed to strong light and hign temperature . The tablets and pellets are stable in 40 °C and RH75%. The next work is to investigate the release behavior in vivo and its correlation with in vitro .