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Probing the Thermal Transitions of Lactobionic Acid and Effects of Sample History by DSC Analysis
Journal of Pharmaceutical Sciences xxx (2019) 1-4
Contents lists available at ScienceDirect
Journal of Pharmaceutical Sciences journal homepage: www.jpharmsci.org
Rapid Communication
Probing the Thermal Transitions of Lactobionic Acid and Effects of Sample History by DSC Analysis Leno Mascia 1, *, Alessandro Coroli 1, 2, Elisa Mele 1 1 2
Department of Materials, Loughborough University, Loughborough LE3 TU, UK di Bologna, 44121 Bologna, Italy Department of Civil, Chemical, Environmental and Materials Engineering, Universita
a r t i c l e i n f o
a b s t r a c t
Article history: Received 2 July 2019 Revised 5 September 2019 Accepted 18 September 2019
We report the results of an ad hoc evaluation of the thermal transition and physical state of lactobionic acid, carried out by differential scanning calorimetry, which was motivated by the confusion about its physical state in relation to the “melting point”. This work establishes that lactobionic acid is a molecular glass characterized by a glass-liquid transition at around 125 C and 2 minor transitions, respectively, at around 70 C and 40 C. The temperature at which these latter transitions appear and the intensity of the enthalpic peaks, associated with physical aging, are sensitive to the thermal history of the sample and to the presence of small quantities of absorbed water. © 2019 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.
Keywords: antiplasticization lactobionic acid molecular glass physical aging thermal analysis
Introduction Lactobionic acid (LBA), corresponding to 4-O-b-D-galactopyranosyl-D-gluconic acid, is a versatile polyhydroxy acid with numerous existing and potentially new applications in the food, medicine, pharmaceutical, cosmetics, and chemical industries.1-4 There are inconsistent data for the “melting point”, which is quoted by suppliers to be 113 C-118 C (e.g., SigmaeAldrich, Molbase, Chemical Book) and approximately 125 C (Global Calcium), while published work quotes a value of 128 C-130 C1 and reveals some unusual features about thermal transitions.5 We are reporting observations and insights derived from ad hoc experiments carried out with the view of clarifying the melting point issue, probing at the same time the possible effects of the environmental history of the sample under examination.
Experimental Procedures The essential details of the thermal analysis by differential scanning calorimetry (DSC) used in this work are as follows: LBA (97% purity) was obtained from Sigma-Aldrich, UK; * Correspondence to: Leno Mascia (Telephone: 44(0)1509 228595). E-mail address: [email protected] (L. Mascia).
Experiments were carried out in nitrogen atmosphere at 50 mL/ min flow rate, using a DSC Q20 V24.11 Build 124 instrument equipped with Universal V4.5A TA Instruments software. Sample weight was 2-6 mg and cold-sealed (not hermetically). A standard indium calibration was carried out (PN 915060.901). We have explored the possibility of “externally” inducing the crystallization of LBA, which would be expected to produce a distinct enthalpy peak in the region of 113 C-118 C if the “melting point” quoted by some suppliers is a thermodynamic melting transition. To this end, 2 samples were melted in an oven at 125 C for 15 min. One sample was then cooled down to 105 C and the other to 90 C. Both were isothermally “annealed” at these temperatures for 30 min before being cooled to room temperature for testing (crystallization from the melt). At the same time, an LBA sample was physically mixed at cold temperature with 10 w% talc (known to be an efficient nucleating agent)6 and then subjected to an isothermal treatment at 105 C for 30 min (nucleated cold crystallization). (The talc used is a noncoated grade, known commercially as Talc S2-200, donated by LKAB Minerals). The revelation of the loss of small amount of water at around 100 C in previous work5 alludes to a possible plasticization effect by absorbed water. This has prompted us to probe the effect of atmospheric moisture on samples of LBA after 7 days exposure to ambient laboratory conditions and to examine the sensitivity of the
https://doi.org/10.1016/j.xphs.2019.09.017 0022-3549/© 2019 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.
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L. Mascia et al. / Journal of Pharmaceutical Sciences xxx (2019) 1-4
Figure 1. (a) DSC thermograms from this study. (b) Appearance of samples of LBA heated in an oven, respectively, at 105 C and 125 C and tilted by 90 at room temperature.
identified transitions and corresponding enthalpic peaks to the heating rate used in the DSC runs. The atmospheric conditions of the laboratory are 50%-65% RH and temperature controlled to 22 C. To examine further the effects of moisture on the physical state of LBA, samples were prepared by physically mixing at cold temperature the “as received” material with 1 wt% water. A different
sample of this mixture, contained in open glass bottles (2.5 cm diameter), was heated in an oven at 90 C for 60 min and then at 105 C for 60 min before being removed and cooled down to room temperature. At the same time, an LBA film (about 0.3 mm thick) was cast from a 20 wt% water solution and dried at room temperature for 40 days before testing.
Figure 2. Heating rate effects on thermograms for (a) “as received” LBA sample and (b) “ambient conditioned” LBA sample. Plots of enthalpy (c) and T*b (d) against heating rate for “as received” LBA sample (black symbols) and “ambient conditioned” LBA sample (open symbols).
L. Mascia et al. / Journal of Pharmaceutical Sciences xxx (2019) 1-4
3
Results and Discussion In Figure 1a, first- and second-cycle DSC thermograms obtained on an “as received” sample of LBA supplied by Sigma-Aldrich are shown. These reveal an enthalpic peak at 70 C and a “mild” transition at around 38 C in the first heating cycle and a very broad transition with a midpoint at 73 C in the second heating cycle. A one-cycle run made at 10 C/min from 80 C to þ20 C has revealed no additional transitions other than a very small “step” at around 0.7 C, which can be attributed to traces of segregated water in the sample dissolving into the LBA matrix. In Figure 1b are shown photographs of 2 bottles of samples of LBA “as received” heated at 2 different temperatures and then tilted by 90 at room temperature. The photographs make it evident that LBA is a viscous liquid (melt) at 125 C and that the particles lose the “free-flowing” characteristics even at 105 C, which may be attributed to the lower surface Tg of the particles as for the case of thin films,7 an effect that might have been accentuated by moisture induced plasticization. The absence of a “significant” thermodynamic melting peak at any temperature below 150 C suggests that fusion/sintering of the sample heated in the oven at 125 C can only be associated with a glass-liquid transition. The comparison of the related thermograms with those for the “as received” samples is shown in Figures 2a and 2b. The data reported in the plots in Figures 2c and 2d bring out some fundamental connotations in relation to the effects of absorbed water, which is manifest as an increase in both relaxation enthalpy and transition peak temperature (referred to as “nominal b transition temperature”, T*b) and can be attributed to an antiplasticization effect. The concomitant crossover in the T*b trend line that is observed at low heating rates, on the other hand, is indicative of a “switch” to plasticization.8,9 The DSC thermograms obtained at 20 C/min heating rates are shown in Figure 3. No evidence of induced crystallization can be detected from an inspection of the related thermograms in all cases, and therefore, it is deduced that talc acts primarily as an “inert filler” with respect to the heat capacity of the sample. It means that because the Cp value of talc is constant over the temperature range examined,10 the effect in the DSC signal is manifest as a 10% reduction in heat capacity, which has been accounted for in the thermogram as a normalized sample weight. Nevertheless, the thermograms indicate that the presence of talc is responsible for a 5 C upward shift of the transition with a peak at around 75 C and an increase in the related relaxation enthalpy through “assisted” physical aging. The annealing step at 90 C for the sample without talc, on the other hand, brings about the emergence of a physical aging relaxation peak at around 50 C.11,12 The thermograms obtained at heating rate of 20 C/min, shown in Figure 4a, reveal the presence of endotherm spikes at temperatures above 125 C for the 2 water-containing samples that were not subjected to any heat treatment (curves 1 and 2). The thermogram for the sample mixed with 1 wt% water and then thermally treated in steps at 90 C and 105 C (curve 3, labeled “Dried LBA-1w% H2O) showed a similar glass-liquid transition just above 120 C and 2 “minor” transitions at around 40 C and 60 C; however, the trace is devoid of distinct enthalpic spikes at higher temperatures. The comparison with the thermogram for the LBA “as received” sample, shown in Figure 4a, indicates that the presence of residual water causes not only a displacement of the glass transition to lower temperatures but also a steepening of the glass-liquid transition, which is indicative of an enhanced fragility associated with a plasticization.13 The nature of the transition at the upper temperature end of the spectrum was probed further by running scans on LBA (as received)
Figure 3. Thermograms at 20 C/min heating rate for LBA samples (with and without talc) cooled from 125 C (melt state) and isothermally annealed at 105 C and 90 C.
at different heating rates, using the following routine to provide thermal history uniformity: “Heating from 20 C to 125 C at 30 C/ min, followed by 2 min isothermal before cooling down to 90 C at 30 C/min. After a 2-min isotherm, scans were made at different heating rates from 90 C to 160 C to record the Tg value. Note that the spikey nature of the traces above 145 C can be attributed to thermal decomposition.5 The plot of obtained Tg(i) values versus heating rate, shown in Figure 4b, displays the typical kinetic nature
Figure 4. (a) DSC thermograms for cast LBA film (curve 2); 1 wt% water cold mixed with LBA and tested (curve 1); 1 wt % water mixed with LBA and then oven dried at 90 C and then to 105 C; (curve 3). (b) Plot of Tg(i) values versus heating rate for LBA (as received samples).
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L. Mascia et al. / Journal of Pharmaceutical Sciences xxx (2019) 1-4
of the a-transition of glasses, allowing for the uncertainties in locating the exact position of point where the values were taken. Conclusion The conclusion that can be drawn from this study is that LBA is a molecular organic glass exhibiting a glass-liquid transition at ~125 C for heating rates tending to zero, which can be referred to as the “softening point” or “flow temperature” for practical purposes. It also exhibits 2 minor thermal transitions at around 65 C-70 C (nominal b transition) and at 37 C-40 C (nominal g transition), which result from intramolecular relaxations and are responsible for physical aging induced by thermal treatments below the glassliquid transition. References 1. Alonso S, Rendueles M, Díaz M. Bio-production of lactobionic acid: current status, applications and future prospects. Biotechnol Adv. 2013;31(8):1275-1291. 2. Bharwade MN, Balakrishnan S, Chaudhary NN, Jain AK. Lactobionic acid: significance and application in food and pharmaceutical. Intl J Food Ferment. 2017;6(1):25-33.
3. Rao SS, Rao Appa BV, Kiran SR, Sreedhar B. Lactobionic acid as a new synergist in combination with phosphonate-Zn(II) system for corrosion inhibition of carbon steel. J Mater Sci Technol. 2014;30(1):77-89. 4. Pietrzak E, Wieclaw-Midor A, Wiercinska P, Poterala M, Szafran M. Thermal decomposition of polyhydroxy processing agents dedicated to colloidal shaping of ceramics e Thermogravimetry coupled with mass spectrometry and properties of ZTA composites. Thermochim Acta. 2019;674(4):100-109. 5. Bisinella RZB, Ribeiro JCB, Soltovski de Oliveira C, et al. Some instrumental methods applied in food chemistry to characterise lactulose and lactobionic acid. Food Chem. 2017;220(4):295-298. 6. Mascia L. Polymers in Industry: A Concise Encyclopedia from A-Z. Weinheim, Germany: Wiley-VCH; 2012:221. 7. Dorkenoo KD, Pfromm PH. Accelerated physical aging of thin poly[1-(trimethylsilyl)-1-propyne] films. Macromolecules. 2000;33(10):3747-3751. di D, Tomka I, Escher F. Thermodynamics of amorphous StarchWater 8. Bencze systems. 1. Volume Fluctuations. Macromolecules. 1998;31(9):3055-3061. 9. Dlubek G, Redmann F, Krause-Rehberg R. Humidity induced plasticization and antiplasticization of polyamide 6: a positron lifetime study of the local free volume. J Appl Polym Sci. 2002;84(1):244-255. 10. Robie RA, Stout JW. Heat capacity from 12 to 305 K and entropy of talc and tremolite. J Phys Chem. 1963;67(11):2252-2256. 11. Roth CB, ed. Polymer Glasses. Canada: CRC Press; 2016. 12. Vyavahare O, Ng D, Hsu SL. Analysis of structural rearrangements of poly(lactic acid) in the presence of water. J Phys Chem B. 2015;118(15):4185-4193. 13. Araujo S, Delpouve N, Dhotel A, et al. Reducing the gap between the activation energy measured in the liquid and the glassy states by adding a plasticizer to polylactide. ACS Omega. 2018;3(12):17092-17099.
Contents lists available at ScienceDirect
Journal of Pharmaceutical Sciences journal homepage: www.jpharmsci.org
Rapid Communication
Probing the Thermal Transitions of Lactobionic Acid and Effects of Sample History by DSC Analysis Leno Mascia 1, *, Alessandro Coroli 1, 2, Elisa Mele 1 1 2
Department of Materials, Loughborough University, Loughborough LE3 TU, UK di Bologna, 44121 Bologna, Italy Department of Civil, Chemical, Environmental and Materials Engineering, Universita
a r t i c l e i n f o
a b s t r a c t
Article history: Received 2 July 2019 Revised 5 September 2019 Accepted 18 September 2019
We report the results of an ad hoc evaluation of the thermal transition and physical state of lactobionic acid, carried out by differential scanning calorimetry, which was motivated by the confusion about its physical state in relation to the “melting point”. This work establishes that lactobionic acid is a molecular glass characterized by a glass-liquid transition at around 125 C and 2 minor transitions, respectively, at around 70 C and 40 C. The temperature at which these latter transitions appear and the intensity of the enthalpic peaks, associated with physical aging, are sensitive to the thermal history of the sample and to the presence of small quantities of absorbed water. © 2019 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.
Keywords: antiplasticization lactobionic acid molecular glass physical aging thermal analysis
Introduction Lactobionic acid (LBA), corresponding to 4-O-b-D-galactopyranosyl-D-gluconic acid, is a versatile polyhydroxy acid with numerous existing and potentially new applications in the food, medicine, pharmaceutical, cosmetics, and chemical industries.1-4 There are inconsistent data for the “melting point”, which is quoted by suppliers to be 113 C-118 C (e.g., SigmaeAldrich, Molbase, Chemical Book) and approximately 125 C (Global Calcium), while published work quotes a value of 128 C-130 C1 and reveals some unusual features about thermal transitions.5 We are reporting observations and insights derived from ad hoc experiments carried out with the view of clarifying the melting point issue, probing at the same time the possible effects of the environmental history of the sample under examination.
Experimental Procedures The essential details of the thermal analysis by differential scanning calorimetry (DSC) used in this work are as follows: LBA (97% purity) was obtained from Sigma-Aldrich, UK; * Correspondence to: Leno Mascia (Telephone: 44(0)1509 228595). E-mail address: [email protected] (L. Mascia).
Experiments were carried out in nitrogen atmosphere at 50 mL/ min flow rate, using a DSC Q20 V24.11 Build 124 instrument equipped with Universal V4.5A TA Instruments software. Sample weight was 2-6 mg and cold-sealed (not hermetically). A standard indium calibration was carried out (PN 915060.901). We have explored the possibility of “externally” inducing the crystallization of LBA, which would be expected to produce a distinct enthalpy peak in the region of 113 C-118 C if the “melting point” quoted by some suppliers is a thermodynamic melting transition. To this end, 2 samples were melted in an oven at 125 C for 15 min. One sample was then cooled down to 105 C and the other to 90 C. Both were isothermally “annealed” at these temperatures for 30 min before being cooled to room temperature for testing (crystallization from the melt). At the same time, an LBA sample was physically mixed at cold temperature with 10 w% talc (known to be an efficient nucleating agent)6 and then subjected to an isothermal treatment at 105 C for 30 min (nucleated cold crystallization). (The talc used is a noncoated grade, known commercially as Talc S2-200, donated by LKAB Minerals). The revelation of the loss of small amount of water at around 100 C in previous work5 alludes to a possible plasticization effect by absorbed water. This has prompted us to probe the effect of atmospheric moisture on samples of LBA after 7 days exposure to ambient laboratory conditions and to examine the sensitivity of the
https://doi.org/10.1016/j.xphs.2019.09.017 0022-3549/© 2019 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.
2
L. Mascia et al. / Journal of Pharmaceutical Sciences xxx (2019) 1-4
Figure 1. (a) DSC thermograms from this study. (b) Appearance of samples of LBA heated in an oven, respectively, at 105 C and 125 C and tilted by 90 at room temperature.
identified transitions and corresponding enthalpic peaks to the heating rate used in the DSC runs. The atmospheric conditions of the laboratory are 50%-65% RH and temperature controlled to 22 C. To examine further the effects of moisture on the physical state of LBA, samples were prepared by physically mixing at cold temperature the “as received” material with 1 wt% water. A different
sample of this mixture, contained in open glass bottles (2.5 cm diameter), was heated in an oven at 90 C for 60 min and then at 105 C for 60 min before being removed and cooled down to room temperature. At the same time, an LBA film (about 0.3 mm thick) was cast from a 20 wt% water solution and dried at room temperature for 40 days before testing.
Figure 2. Heating rate effects on thermograms for (a) “as received” LBA sample and (b) “ambient conditioned” LBA sample. Plots of enthalpy (c) and T*b (d) against heating rate for “as received” LBA sample (black symbols) and “ambient conditioned” LBA sample (open symbols).
L. Mascia et al. / Journal of Pharmaceutical Sciences xxx (2019) 1-4
3
Results and Discussion In Figure 1a, first- and second-cycle DSC thermograms obtained on an “as received” sample of LBA supplied by Sigma-Aldrich are shown. These reveal an enthalpic peak at 70 C and a “mild” transition at around 38 C in the first heating cycle and a very broad transition with a midpoint at 73 C in the second heating cycle. A one-cycle run made at 10 C/min from 80 C to þ20 C has revealed no additional transitions other than a very small “step” at around 0.7 C, which can be attributed to traces of segregated water in the sample dissolving into the LBA matrix. In Figure 1b are shown photographs of 2 bottles of samples of LBA “as received” heated at 2 different temperatures and then tilted by 90 at room temperature. The photographs make it evident that LBA is a viscous liquid (melt) at 125 C and that the particles lose the “free-flowing” characteristics even at 105 C, which may be attributed to the lower surface Tg of the particles as for the case of thin films,7 an effect that might have been accentuated by moisture induced plasticization. The absence of a “significant” thermodynamic melting peak at any temperature below 150 C suggests that fusion/sintering of the sample heated in the oven at 125 C can only be associated with a glass-liquid transition. The comparison of the related thermograms with those for the “as received” samples is shown in Figures 2a and 2b. The data reported in the plots in Figures 2c and 2d bring out some fundamental connotations in relation to the effects of absorbed water, which is manifest as an increase in both relaxation enthalpy and transition peak temperature (referred to as “nominal b transition temperature”, T*b) and can be attributed to an antiplasticization effect. The concomitant crossover in the T*b trend line that is observed at low heating rates, on the other hand, is indicative of a “switch” to plasticization.8,9 The DSC thermograms obtained at 20 C/min heating rates are shown in Figure 3. No evidence of induced crystallization can be detected from an inspection of the related thermograms in all cases, and therefore, it is deduced that talc acts primarily as an “inert filler” with respect to the heat capacity of the sample. It means that because the Cp value of talc is constant over the temperature range examined,10 the effect in the DSC signal is manifest as a 10% reduction in heat capacity, which has been accounted for in the thermogram as a normalized sample weight. Nevertheless, the thermograms indicate that the presence of talc is responsible for a 5 C upward shift of the transition with a peak at around 75 C and an increase in the related relaxation enthalpy through “assisted” physical aging. The annealing step at 90 C for the sample without talc, on the other hand, brings about the emergence of a physical aging relaxation peak at around 50 C.11,12 The thermograms obtained at heating rate of 20 C/min, shown in Figure 4a, reveal the presence of endotherm spikes at temperatures above 125 C for the 2 water-containing samples that were not subjected to any heat treatment (curves 1 and 2). The thermogram for the sample mixed with 1 wt% water and then thermally treated in steps at 90 C and 105 C (curve 3, labeled “Dried LBA-1w% H2O) showed a similar glass-liquid transition just above 120 C and 2 “minor” transitions at around 40 C and 60 C; however, the trace is devoid of distinct enthalpic spikes at higher temperatures. The comparison with the thermogram for the LBA “as received” sample, shown in Figure 4a, indicates that the presence of residual water causes not only a displacement of the glass transition to lower temperatures but also a steepening of the glass-liquid transition, which is indicative of an enhanced fragility associated with a plasticization.13 The nature of the transition at the upper temperature end of the spectrum was probed further by running scans on LBA (as received)
Figure 3. Thermograms at 20 C/min heating rate for LBA samples (with and without talc) cooled from 125 C (melt state) and isothermally annealed at 105 C and 90 C.
at different heating rates, using the following routine to provide thermal history uniformity: “Heating from 20 C to 125 C at 30 C/ min, followed by 2 min isothermal before cooling down to 90 C at 30 C/min. After a 2-min isotherm, scans were made at different heating rates from 90 C to 160 C to record the Tg value. Note that the spikey nature of the traces above 145 C can be attributed to thermal decomposition.5 The plot of obtained Tg(i) values versus heating rate, shown in Figure 4b, displays the typical kinetic nature
Figure 4. (a) DSC thermograms for cast LBA film (curve 2); 1 wt% water cold mixed with LBA and tested (curve 1); 1 wt % water mixed with LBA and then oven dried at 90 C and then to 105 C; (curve 3). (b) Plot of Tg(i) values versus heating rate for LBA (as received samples).
4
L. Mascia et al. / Journal of Pharmaceutical Sciences xxx (2019) 1-4
of the a-transition of glasses, allowing for the uncertainties in locating the exact position of point where the values were taken. Conclusion The conclusion that can be drawn from this study is that LBA is a molecular organic glass exhibiting a glass-liquid transition at ~125 C for heating rates tending to zero, which can be referred to as the “softening point” or “flow temperature” for practical purposes. It also exhibits 2 minor thermal transitions at around 65 C-70 C (nominal b transition) and at 37 C-40 C (nominal g transition), which result from intramolecular relaxations and are responsible for physical aging induced by thermal treatments below the glassliquid transition. References 1. Alonso S, Rendueles M, Díaz M. Bio-production of lactobionic acid: current status, applications and future prospects. Biotechnol Adv. 2013;31(8):1275-1291. 2. Bharwade MN, Balakrishnan S, Chaudhary NN, Jain AK. Lactobionic acid: significance and application in food and pharmaceutical. Intl J Food Ferment. 2017;6(1):25-33.
3. Rao SS, Rao Appa BV, Kiran SR, Sreedhar B. Lactobionic acid as a new synergist in combination with phosphonate-Zn(II) system for corrosion inhibition of carbon steel. J Mater Sci Technol. 2014;30(1):77-89. 4. Pietrzak E, Wieclaw-Midor A, Wiercinska P, Poterala M, Szafran M. Thermal decomposition of polyhydroxy processing agents dedicated to colloidal shaping of ceramics e Thermogravimetry coupled with mass spectrometry and properties of ZTA composites. Thermochim Acta. 2019;674(4):100-109. 5. Bisinella RZB, Ribeiro JCB, Soltovski de Oliveira C, et al. Some instrumental methods applied in food chemistry to characterise lactulose and lactobionic acid. Food Chem. 2017;220(4):295-298. 6. Mascia L. Polymers in Industry: A Concise Encyclopedia from A-Z. Weinheim, Germany: Wiley-VCH; 2012:221. 7. Dorkenoo KD, Pfromm PH. Accelerated physical aging of thin poly[1-(trimethylsilyl)-1-propyne] films. Macromolecules. 2000;33(10):3747-3751. di D, Tomka I, Escher F. Thermodynamics of amorphous StarchWater 8. Bencze systems. 1. Volume Fluctuations. Macromolecules. 1998;31(9):3055-3061. 9. Dlubek G, Redmann F, Krause-Rehberg R. Humidity induced plasticization and antiplasticization of polyamide 6: a positron lifetime study of the local free volume. J Appl Polym Sci. 2002;84(1):244-255. 10. Robie RA, Stout JW. Heat capacity from 12 to 305 K and entropy of talc and tremolite. J Phys Chem. 1963;67(11):2252-2256. 11. Roth CB, ed. Polymer Glasses. Canada: CRC Press; 2016. 12. Vyavahare O, Ng D, Hsu SL. Analysis of structural rearrangements of poly(lactic acid) in the presence of water. J Phys Chem B. 2015;118(15):4185-4193. 13. Araujo S, Delpouve N, Dhotel A, et al. Reducing the gap between the activation energy measured in the liquid and the glassy states by adding a plasticizer to polylactide. ACS Omega. 2018;3(12):17092-17099.