Anhydride prodrug of ibuprofen and acrylic polymers.
The objective of this study was to synthesize anhydride prodrugs for carboxylic-acid-bearing agents such as non-steroidal anti-inflammatory drugs, shield the carboxylic acid group from irritative effects, and obtain sustained release patterns. Ibuprofen was used as a representative drug for anhydride derivatization. Conjugates of ibuprofen with carboxylic acid moieties of different acrylic polymers were prepared by dehydration reaction using acetic anhydride. Products were characterized by infrared spectroscopy, nuclear magnetic resonance, and scanning electron microscopy followed by preparation of microspheres with different sizes from the conjugate Eudragit L-100-ibuprofen. The drug release was monitored by high-performance liquid chromatography. Ibuprofen was bound to the polymers via an anhydride bond in high reaction yields (75-95%) with drug loading of up to 30% (w/w). These anhydride derivatives hydrolyzed and release the drug at different periods ranging from 1 to 5 days, depending on the hydrophobicity and the cross-linking of the conjugates. The release of drug from the microspheres was correlated to their size and ranged from 2 to almost 8 days. This study demonstrates the promise of anhydride prodrug for extending drug action while shielding the carboxylic acid group.
Mizrahi
Boaz
B
Department of Medicinal Chemistry and Natural Products, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, 91120, Israel.
Domb
Abraham J
AJ
D003692:Delayed-Action Preparations; D007052:Ibuprofen / Q000008:administration & dosage / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008863:Microspheres; D011109:Polymethacrylic Acids / Q000008:administration & dosage* / Q000737:chemistry; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry; D012995:Solubility
D003692:Delayed-Action Preparations; D011109:Polymethacrylic Acids; D011355:Prodrugs; C038300:methylmethacrylate-methacrylic acid copolymer; D007052:Ibuprofen