Articles A Quantitative Method for Determination of Lactide Composition in Poly(lactide) Using 1 H NMR Khalid A. M. Thakur,* Robert T. Kean, and Eric S. Hall Central Research, Cargill Incorporated, P.O. Box 5699, Minneapolis, Minnesota 55440 Matthew A. Doscotch and Eric J. Munson* Department of Chemistry, University of Minnesota, 207 Pleasant Street SE, Minneapolis, Minnesota 55455 A method has been developed to quantitatively determine the composition of D-lactide and meso-lactide stereoiso- mer impurities in poly(lactide) containing predominantly L-lactide. In this method, the stereosequence information obtained from a few well-resolved resonances in the 1 H NMR spectrum representing RR and R stereogenic de- fects is used. The D-lactide and meso-lactide as minor components lead to RR and R stereogenic defects, respectively, which influence the isotactic chain length distribution and hence affect the polymer properties. Analytical equations relating the stereosequence prob- ability to the lactide feed composition are not available due the complicated kinetics involved for the melt polym- erization; viz. the preference for syndiotactic lactide ad- dition decreases with reducing residual lactide concen- tration in the batch process. Hence, empirical correlations were determined by least-squares fit to the predictions for the specific stereosequence probabilities provided by Monte Carlo calculations of a number of lactide stereo- copolymerizations. The Monte Carlo calculations simulate the kinetics observed for melt polymerization at 180 °C catalyzed by Sn(II) bis(2-ethylhexanoate) (Sn(II) octoate) in a 1:10 000 catalyst/lactide ratio. Poly(lactide) is a well-known bioresorbable polymer which has been explored for use in several biomaterials applications and drug delivery systems, including in vivo degradable/resorbable medical implants and sutures. 1-4 Due to its biodegradability and ecosystem- friendly properties, 2,5 poly(lactide) (PLA, Chart 1) can also be an ideal replacement for nondegradable polymers in numerous applications such as yard waste bags, food containers, agricultural mulch films, etc. Recent technological developments have made PLA products economically competitive with petroleum-derived plastics. 6,7 High molecular weight PLA is prepared by ring-opening polymerization 8-11 of lactic acid cyclic dimers (lactides) which exist as RR, SS, or RS stereoisomers. The RR configuration of the cyclic dimer is referred to as D-lactide while the SS configuration is referred to as L-lactide. An equimolar ratio of (RR)- and (SS)- lactide is referred to as racemic or D,L-lactide, and the (RS)-lactide is referred to as meso-lactide. A number of physical properties of PLA are linked to its stereosequence distribution. 7,12-14 For example, pure isotactic poly(L-lactide) (PLLA) crystallizes at a faster rate and to a larger extent than when L-lactide is polymerized with small amounts of either D-lactide or meso-lactide. 7,13 Hence the isotactic S length distribution, which is determined primarily by the amount of L-lactide in PLA, may be linked to its crystallization properties. 13,15,16 In the polymer, to a first approximation, the lactide stereoisomer composition may be used to represent the stereosequence distribution. (1) Vert, M.; Schwarch, G.; Coudane, J. J. Macromol. Sci. Pure Appl. Chem. 1995, A32, 787-796. (2) Miyoshi, R.; Hashimoto, N.; Koyanagi, K.; Sumihiro, Y.; Sakai, T. Int. Polym. Process. 1996, 11, 320-328. (3) Mainilvarlet, P.; Rahm, R.; Gogolewski, S. 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(13) Thakur, K. A. M.; Kean, R. K.; Zupfer, J.; Buehler, N.; Doscotch, M. A.; Munson, E. J. Macromolecules 1996, 29, 8844-8851. (14) Sanchez, I. C.; Eby, R. K. J. Res. Nat. Bur. Std. (U.S.) 1973, 77A, 353- 358. (15) Macdonald, R. T.; McCarthy, S. P.; Gross, R. A. Macromolecules 1996, 29, 7356-7361. (16) Tsuji, H.; Ikada, Y. Macromol. Chem. Phys. 1996, 197, 3483-3499. Chart 1 Anal. Chem. 1997, 69, 4303-4309 S0003-2700(97)00792-0 CCC: $14.00 © 1997 American Chemical Society Analytical Chemistry, Vol. 69, No. 21, November 1, 1997 4303