تهيه و بررسي رفتار هيدروليزي مشتقات پلي اتيلن گليكول - ايبوبروفن

Preparation and study of hydrolytic behavior of PEGylated derivatives of ibuprofen

Three kinds of PEGylated derivatives of ibuprofen have been prepared and their hydrolytic behavior have been studied in aqueous buffered solutions ( pH 1, 7.8 , 4).The PEGylated derivatives of ibuprofen comprised of the low molecular weight derivatives of the drug and poly ethylene glycol (PEG) units connected by labile ester, amide, or thioester bonds. Ibuprofen converted to its hydroxyethyl ester (HEE), hydroxyethyl amide (HEA), or ydroxyethyl thioester (HETA) derivatives and coupled to monomethoxy polyethylene glycol mono succinate (PEG- COOH). All three PEGylated derivatives of ibuprofen released the drug gradually as a function of time and pH. In HEE- PEG the amount of released drug was lower, while the difference between acidic and alkali buffered solutions was not as large. HETE- PEG in acidic medium ibuprofen released to a much smaller extent than in basic medium. HEA- PEG had a notable stability in buffered solutions and showed a small acceleration of hydrolysis rate in human plasma due to the catalysis by esterases present in the plasma.