CALCULATION OF HYDROLYTIC RATE CONSTANTS OF POLY(ORTHO ESTER)S FROM MOLECULAR-WEIGHTS DETERMINED BY GEL-PERMEATION CHROMATOGRAPHY

Purpose. To obtained rate constants from weight-averaged (M(w)) or z-a veraged (M(z)) molecular weights for polymers of Schule-Flory distribu tion and undergoing random scission. These constants were compared wit h those obtained by parallel (1)HNMR studies. Methods. The hydrolysis of two poly(ortho ester)s were followed by (1)HNMR and gel permeation chromatography (GPC). Results. Equations to convert number-averaged (M (n)), M(w) and M(z) into fraction of backbone remaining (f(c)) were de rived. First-order hydrolytic rate constants of two poly(ortho ester)s ; DETOSU-HD and DETOSU-CDM were calculated using these relationships. The rate constants calculated from (1)HNMR, M(z) and M(w) were 0.215, 0.218 and 0.182 hr(-1), respectively, for DETOSU-CDM and 0.152, 0.086 and 0.038 hr(-1) for DETOS U-HD. The large discrepancy in the rates de termined by (1)HNMR and GPC in the latter case was attributed to that the detector response (refractive index) of the monomers was lower tha n that of the high molecular weight polymer. The difference is small i n the case of DETOSU-CDM, and the rates calculated from GPC data were comparable or nearly identical to that obtained from (1)HNMR data. Con clusions. Although GPC can yield rapid and valuable kinetic data for t he degradation of biodegradable polymers, the system, however, must be carefully calibrated to account for the variations in Mark-Houwink co efficients and in the response of the mass detector between the high a nd low MW polymers.