SYNTHESIS AND PROPERTIES OF COPOLYMERS FROM 2-HYDROXYETHYL METHACRYLATE-LINKED NONSTEROIDAL ANTIINFLAMMATORY AGENTS WITH METHACRYLIC-ACID

Three nonsteroidal antiinflammatory drugs, 2-(4-isobutylphenyl)-propio nic acid (ibuprofen), 2-(3-benzoylphenyl)-propionic acid (ketoprofen), and 2-(6-methoxy-2-naphthyl) -propionic acid (naproxen), were covalen tly linked with 2-hydroxyethyl methacrylate (HEMA). The drug-linked HE MA (M-1) (ibuprofen-linked HEMA abbreviated as HI; ketoprofen-inked HE MA. as HK, and naproxen-linked HEMA as HN),were respectively copolymer ized with methacrylic acid(M-2), MA, to obtain macromolecular prodrugs . The compositions of the copolymers were determined by means of a H-1 -NMR spectroscopy and monomer reactivity ratios were estimated. using the Kelen-Tudos linear differential equation. The reactivity ratios ar e: r(1) = 0.101 +/- 0.012, r(2) = 1.071 +/- 0.065 for HI-MA; r(1) = 0. 344 +/- 0.066, r(2) = 0.966 +/- 0.032 for HN-MA, and r(1) = 0.650 +/- 0.182, r(2) = 1.032 +/- 0.106 for HK-MA, respectively. The monomer rea ctivity toward to MA radical estimated from 1/r(2) values is almost sa me for all three monomers (1/r(2) similar to 1). The glass transition temperatures of three drug-linked homopolymers go hand in hand with th e steric hindrance of three drugs, i.e., ketoprofen > naproxen much gr eater than ibuprofen calculated the minimum energy by computer molecul ar modeling. (C) 1998 John Wiley & Sons, Inc.