NSAIDs bound to methacrylic carriers: microstructural characterization andin vitro release analysis

Chemically controlled drug delivery systems or 'polymeric drugs' based on c opolymers of a-hydroxyethyl methacrylate, HEMA, and five methacrylic deriva tives which incorporate ibuprofen or ketoprofen in their chemical structure by means of labile ester bonds, MAI, MAK, MAEK, MEI and MEK, have been pre pared by free radical polymerization in solution at 50 degreesC. Three diff erent spacers have been incorporated to the monomer structure: an aromatic amide, an aliphatic eater and a combined aromatic amide/aliphatic ester. Co polymerization reactions of the methacrylamide derivatives with HEMA follow the terminal model with reactivity ratio values, determined by the Tidwell and Mortimer (J. Polym. Sci. A 1965;3:369-378) non-linear least-squares tr eatment, of r(MAI)=0.38, r(HEMA)=1.69; r(MAK)=0.30, r(HEMA)=0.48; and r(MAE K)=0.66, r(HEMA)=2.85. From these values and considering that the methacryl ates MEI and MEK are structurally related to HEMA, the microstructural anal ysis give us a random distribution of the monomeric units. The HEMA-rich co polymers, used for the in vitro experiments, showed a very high population of sequences with the active residue isolated by HEMA units. The in vitro r elease experiments were carried out at pH 7.4 and 9, using six different co mpositions for each copolymer system (1, 2.5, 5, 10, 20 and 30 wt% of the a ctive acrylic monomer). The results show a controlled release in terms of w eeks with very different profiles which depend on the type of spacer (the a romatic ester is more susceptible to hydrolysis than the aliphatic one), dr ug (ketoprofen release rate is higher than the ibuprofen one), composition of the copolymer las a general rule, the release rate increases with the co ntent of the attached drug until some composition where this effect is reve rted because of the global increase in hydrophobicity) and pH (the release rate is noticeably higher in a strong basic medium, pH 9). (C) 2001 Elsevie r Science B.V. All rights reserved.