Direct Synthesis of Polylactide (PLA)-Chlorphenesin Prodrug and Optimization Thereof with the Aid of DOE

A direct, one-pot, solvent-free method for preparation of macromolecular prodrug composed of chlorphenesin (CF, 1) and polylactide (2) was developed. The procedure involves addition of chlorphenesin to l-lactide followed by ring-opening polymerization of the latter. The process was optimized by factorial design to maximize the conversion and to obtain sufficiently high average molecular mass of the prodrug. Proposed mathematical model allows the length of the polymeric chain to be controlled, influencing the duration of the therapeutic effect.