A 3(2) factorial design investigation to optimize N-carboxybutylchitosan was carried out varying the levulinic acid/chitosan molar ratio between 1.00 and 3.00 and the sodium borohydride/chitosan molar ratio from 0.50 to 1.00. H-1 NMR spectra signals at 1.0 and 2.5 ppm were used to monitor the reaction system. A quadratic model having significant terms for both molar ratios was found for N-carboxybutylchitosan substitution degree whereas a linear model best describes the substitution degree of 5-methylpyrrolidinone chitosan. Maximum N-carboxybutylchitosan and minimum 5-methylpyrrolidinone chitosan substitution degrees occur for levulinic acid/chitosan molar ratios between 2.00 and 3.00 and a 0.50 for sodium borohydride/chitosan molar ratio. (C) 2004 Elsevier Ltd. All rights reserved.5913742