Synthesis and hydrolytic behavior of ibuprofen prodrugs and their PEGylated derivatives.
Polyethylene glycol (PEG) derivatives of ibuprofen were prepared by esterification of PEG monosuccinate with hydroxy ethyl ester (HEE), hydroxy ethylamide (HEA), and hydroxy ethyl thioester (HET) of ibuprofen. Hydrolysis of HEE-PEG, HEA-PEG, and HET-PEG were studied in vitro with or without esterases to investigate the applicability of these PEGylated prodrugs. The polymeric prodrugs released major fraction of the parent drug (ibuprofen) and a small fraction of hydroxy ethyl derivatives after 48 hr. In HET-PEG, the amount of drug release was higher than HEE-PEG and HEA-PEG. The difference between acidic and alkali buffered solutions was considerable. In human plasma, 50% of drug was released after 150 hr incubation at 37 degrees C from HET-PEG.
Davaran
Soodabeh
S
Drug Applied Research Centre, Tabriz University of Medical Sciences, Tabriz, Iran. davaran@tbzmed.ac.ir
Rashidi
Mohammad Reza
MR
Hanaee
Jalal
J
Hamidi
Ali A
AA
Hashemi
Mahdi
M
D000577:Amides / Q000737:chemistry; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D004337:Drug Carriers; D004950:Esterases / Q000378:metabolism; D005019:Ethyl Ethers / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007052:Ibuprofen / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*; D007259:Infrared Rays; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D011092:Polyethylene Glycols / Q000737:chemistry*; D011355:Prodrugs / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*; D013440:Sulfides / Q000737:chemistry; D013696:Temperature; D013997:Time Factors
D000577:Amides; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004337:Drug Carriers; D005019:Ethyl Ethers; D011355:Prodrugs; D013440:Sulfides; D011092:Polyethylene Glycols; D004950:Esterases; D007052:Ibuprofen