Rapid Crystallization and Mesophase Formation of Poly(L-Lactic Acid)

e-Polymers 2018; 18(4): 331–337

Muhammad Syazwan and Takashi Sasaki* Rapid crystallization and mesophase formation of poly(L-lactic acid) during precipitation from a solution https://doi.org/10.1515/epoly-2017-0247 is to control the degree of crystallinity. However, it has Received November 24, 2017; accepted January 13, 2018; previously been revealed that PLLA is rather intractable because of published online February 14, 2018 its slow crystallization tendency compared with common crystallizable polymers (1, 2). Efforts have been under- Abstract: Very rapid crystallization behaviors of taken to overcome this problem. Nucleation agents poly(L-lactic acid) (PLLA) are observed at room tempera- and plasticizers are often used as common methods to ture when it is precipitated from a chloroform solution into promote the crystallization (3–7). Other techniques such a large amount of alcohols (non-solvents). The resulting as freeze-drying (8, 9), and solvent-induced crystalliza- crystalline phase contains both a highly ordered (α) and tion (10) have also been reported. In addition, it is worth less ordered (α′) modifications, and the fraction of these noting that interface and geometrical nano-confinement phases depends on the alcohols used as the non-solvents: significantly affect the crystallization process of PLLA methanol tends to produce the highly ordered phase. The (11–14). degree of crystallinity tends to be high for lower alcohols. To promote the polymer crystallization rate, it is When the precipitation occurs in n-hexane, almost no important to clarify its fundamental mechanism. It has crystalline phase is formed, but a mesomorphic phase is been reported that a mesomorphic phase (mesophase), formed as a precursor to the crystalline phase. The results which is an intermediately ordered phase, plays an suggest that the hydroxyl group of alcohols tends to pro- important role in the pathway of polymer crystalliza- mote the crystallization of PLLA. However, it is found that tion as a precursor of a crystalline state (15–20). As its the precipitation in methanol at lower temperatures, such existence has been evidenced for some polymers, the as 0°C, does not yield any crystalline phase. It is suggested issue of the mesophase has evoked new understand- that the present rapid crystallization during precipitation ings for polymer crystallization kinetics, and there has originates from the enhanced mobility of PLLA molecules been much discussion on this issue for various polymers in a metastable (non-equilibrium) liquid state. (21–25). The mesophase for PLLA has been assigned by Keywords: crystallization; FTIR; mesophase; PLLA; using Fourier transform infrared (FTIR) spectroscopy precipitation. (26–29), and furthermore, it has been evidenced that a rapid crystallization of PLLA is achieved through the

mesophase that was formed by supercritical CO2 treat- ment (30). In addition, a strain-induced mesophase for 1 Introduction PLLA was found to occur, which significantly affects the crystalline structure that is formed after a succeeding Poly(L-lactic acid) (PLLA) is known as one of the most annealing (31). common biodegradable and biocompatible polymers. For In this study, we found that crystallization of PLLA broader applications of PLLA as a multi-purpose plastic occurs very rapidly at room temperature during the pre- material, it is necessary to modify its physical properties. cipitation process from a PLLA/chloroform solution into One practical technique for the modification of PLLA non-solvents possessing a hydroxyl group (alcohols). On the other hand, precipitation from the PLLA solution into n-hexane does not induce apparent crystallization; *Corresponding author: Takashi Sasaki, Department of Materials however, the formation of the mesophase is observed. The Science and Engineering, University of Fukui, 3-9-1 Bunkyo, precipitation phenomenon may include two processes, i.e. Fukui, 910 8507, Japan, e-mail: [email protected]. phase separation and crystallization. The rapid crystalli- http://orcid.org/0000-0002-8079-532X Muhammad Syazwan: Department of Materials Science and zation observed in the precipitation in alcohols concerns Engineering, University of Fukui, 3-9-1 Bunkyo, Fukui, 910 8507, the interplay between these two processes. Discussion on Japan this point will be presented. 332 M. Syazwan and T. Sasaki: Rapid crystallization and mesophase formation of PLLA during precipitation

2 Experimental The conventional DSC scan was done at a rate of 40 K min−1 for both heating and cooling. Wide-angle X-ray dif-

PLLA (Mw = 210 kDa, 98% L units) supplied from Mitsui fraction (WAXD) measurements were performed by using Chemicals Co., Tokyo, Japan, was dissolved in chloroform a Rigaku (Tokyo, Japan) RINT2100 equipped with a CuKα (Nacalai Tesque, Kyoto, Japan) with stirring for 72 h at room radiation source (λ = 0.1542 nm). FTIR spectroscopy was temperature to make a 5.0 wt% homogeneous solution. We performed by using a Nicolet 6700 (Thermo Fisher Sci- used n-hexane (Nacalai Tesque, Kyoto, Japan), methanol entific, Waltham, MA, USA) infrared spectrometer. For (Kanto Chemicals, Tokyo, Japan), ethanol (Wako Chemi- transmission measurements of FTIR, the precipitated cals, Osaka, Japan), n-propanol (Nacalai Tesque, Kyoto, sample was pressed to yield a translucent sheet. To Japan), and 2-propanol (Wako Chemicals, Osaka, Japan) investigate the crystalline morphology, scanning elec- as non-solvents for PLLA. Precipitation was performed by tron microscopy (SEM) was performed by using a Hitachi pouring 2.0 ml of the PLLA/chloroform solution into 60 ml (Tokyo, Japan) S-2600 microscope operated at 15 kV. To of the non-solvent with constant stirring. The temperature evaluate the phase diagram for the PLLA/chloroform/ was kept constant at different temperatures (–41°C, 0°C, non-solvent system, cloud point measurements were and 30–32°C). The obtained precipitant was separated via performed. Here, the non-solvent was added slowly with filtration, and it was dried under vacuum at room temper- stirring to PLLA/chloroform solutions with fixed PLLA ature for 72 h. The obtained samples with the above non- content of 2.0 wt% and 5.0 wt% till the solution became solvents are referred to as PLLA/Hex, PLLA/MeOH, PLLA/ turbid, thus the cloud point was determined. EtOH, PLLA/nPrOH, and PLLA/2PrOH, respectively. A reference amorphous PLLA was prepared via press-molding at 100 kg cm−2 at 200°C followed by quenching in water at room temperature. 3 Results and Discussion Differential scanning calorimetry (DSC) was performed by using a Perkin Elmer (Waltham, MA, USA) 3.1 Crystallization of PLLAs precipitated in Pyris Diamond calorimeter with an Intra-cooler P2 alcohols cooling system. The temperature was calibrated by using an indium standard, and all of the measurements were Figure 1 shows DSC heating traces for the precipitated done in a nitrogen atmosphere. We performed step-scan PLLAs. There is no exothermic signal between the glass

DSC measurements, a kind of temperature-modulated transition temperature Tg and the melting temperature DSC, as well as conventional DSC scan measurements. In for PLLA/MeOH, PLLA/EtOH, and PLLA/2PrOH. This the step-scan measurements, we repeated a 2.0 K step of indicates that crystallization has sufficiently proceeded heating at a rate of 5.0 K min−1 followed by a temperature in these samples so that any additional crystallization holding period of 1.5 min. Details are described in Ref 8. does not occur during the DSC heating scan. As for PLLA/ nPrOH, only a subtle exotherm is observed, as indicated by an arrow. Figure 2 shows WAXD profiles of the PLLAs precipitated in alcohols. Diffraction peaks that corre- spond to (200)/(110) and (203) reflections are clearly observed, confirming the crystallinity for these samples. We should also note that for PLLA/MeOH exhibits (210) reflection, which suggests an ordered crystalline structure of PLLA that is often referred to as α modification (32–34). Indeed, the (210) reflection is very sensitive to the ordered α phase (32), and the appearance of this reflection peak in Figure 2 implies that the α phase is at least partially included in PLLA/MeOH. It has been reported that the ordered α structure occurs when PLLA is crystal- lized at low supercoolings, i.e. when the crystallization temperature is higher than 120°C. While at temperatures Figure 1: DSC heating traces for precipitated PLLAs in non-solvents ° α′ at 30°C. lower than 120 C a less ordered crystalline structure ( The heating rate was 40 K min−1. The arrow indicates a slight exo- modification) is usually formed (35). It may be surpris- thermic peak observed for PLLA/nPrOH. ing that the present precipitation method produces the M. Syazwan and T. Sasaki: Rapid crystallization and mesophase formation of PLLA during precipitation 333

Figure 3: FTIR spectra in the range of carbonyl stretching band for precipitated PLLAs in alcohols at 30°C and reference amorphous PLLA.

Figure 2: WAXD profiles for precipitated PLLAs in alcohols at 30°C and reference amorphous PLLA. The curves are vertically shifted. The arrow indicates a small diffraction peak observed for PLLA/Hex.

ordered α crystals at a temperature below Tg. On the other hand, the (210) reflection was found to be subtle (or absent) for the samples with higher alcohols (alcohols with higher number of carbon atoms). However, the peak position for (200)/(110) shifts only slightly to lower Figure 4: FTIR spectra in the range of 840–970 cm−1 for precipitated angle as the alcohol becomes higher, which suggests PLLAs in alcohols at 30°C and reference amorphous PLLA. that the present precipitated PLLAs contain both α and α′ phases. Figure 3 shows FTIR spectra in the region of carbonyl Table 1: Crystallinity of the precipitated PLLAs obtained from DSC and FTIR measurements. stretching band for PLLAs precipitated in alcohols. We observe a shoulder at 1749 cm−1, which is assigned to the Non-solvent X (%) α crystalline structure (36, 37). The shoulder is weakened c as the number of carbons in the alcohol becomes higher, DSC FTIR thus it is suggested that the ordered crystal phase tends to MeOH 43 47 be formed in lower alcohols such as methanol. This is con- EtOH 42 34 sistent with the WAXD results. Anyhow, we infer that the nPrOH 39 28 2PrOH 39 24 precipitated PLLA contains both α and α′ crystals. Figure 4 compares the FTIR spectra of precipitated PLLAs at 30°C, and the amorphous PLLA in the region 840–970 cm−1. The PLLA/MeOH exhibits a crystalline band at 921 cm−1 that which we used a literature value 90.9 J g−1 (38). In addi- has been assigned to a 10/3 helix conformation in the α tion, we evaluated the crystallinity from the FTIR spectra: −1 −1 −1 phase (35). The PLLA/EtOH shows a similar profile to that Xc = A(921 cm )/[A(921 cm ) + A(956 cm )] was used (30), of PLLA/MeOH. where A(921 cm−1) and A(956 cm−1) are absorbance of a

The degree of crystallinity Xc of the precipitated crystalline band and an amorphous band, respectively.

PLLAs was evaluated as (ΔHm–ΔHc)/ΔHm° from DSC The observed crystallinity for PLLA/MeOH is rather high heating traces at 40 K min−1, and the results are shown in and is comparable to that obtained through isothermal

Table 1. Here, ΔHm and ΔHc are the observed exothermic crystallization in a bulk state (37). It is noted that Xc heat and endothermic heat in the heating trace, respec- decreases as the alcohol becomes higher, being consist- tively. ΔHm° is the heat of fusion of PLLA crystal, for ent with the results of WAXD. 334 M. Syazwan and T. Sasaki: Rapid crystallization and mesophase formation of PLLA during precipitation

3.2 Mesophase formation of PLLA precipitated in n-hexane

Contrary to the PLLAs precipitated in alcohols, PLLA/ Hex exhibits almost no signs of crystallization. The DSC heating trace for PLLA/Hex in Figure 1 shows a clear exothermic peak between the Tg and the melting range, sug- gesting a much lower crystallinity than those precipitated in alcohols. Figure 4 shows no apparent (or very weak) absorbance peak at 921 cm−1 for PLLA/Hex. However, a band at 918 cm−1 is observed, which has been assign to the mesophase of PLLA crystalline state (29, 30, 39). This peak was not observed for the amorphous PLLA, thus we con- clude that for PLLA/Hex, only the mesophase formation occurs, and the crystallization is limited during the precipitation. The FTIR result for PLLA/Hex obtained here is consistent with the conventional DSC heating trace shown in Figure 1, which shows little crystallinity. The WAXD profile for the PLLA/Hex in Figure 2 reveals an almost amorphous state but a very small signal of diffraction is observed at 2θ = 16.5°, as indicated by an arrow. This suggests that a small crystalline fraction exists in the PLLA/ Hex sample. As for PLLA/nPrOH, a weaker absorbance −1 band at 921 cm than PLLA/MeOH is observed, and an Figure 5: Step-scan DSC heating traces for PLLA/Hex and amor- absorbance at 918 cm−1 is discernible as well. This implies phous PLLA. that PLLA/nPrOH contains both a crystalline phase and a The solid curves indicate reversing heat capacity, and the dotted mesophase, thus exhibits an intermediate crystallization curves indicate non-reversing heat flow. The arrows indicate cold crystallization signal during the step-scan heating measurement. behavior between PLLA/MeOH and PLLA/Hex. We found that the mesophase formed in PLLA/Hex promotes succeeding crystallization during a heating scan solution state, and the size of crystallites may be much of DSC. Figure 5 shows DSC traces obtained during a step- smaller. It has been reported that crystallization of PLLA scan heating measurement for PLLA/Hex as well as for the from solutions on cooling results in characteristic porous reference amorphous PLLA. An exotherm appears in the spherulites or crystallites, depending on the solvents (40). non-reversing heat flow profile for the PLLA/Hex, which On the contrary, the morphology of the present precipi- indicates that crystallization has not proceeded suffi- tated PLLA is less porous. It is likely that the rapid crys- ciently during the precipitation. However, the exotherm is tallization of the present precipitation process induces a located at a lower temperature for the PLLA/Hex than for high rate of primary nucleation, leading to a large number the amorphous PLLA. Such a low crystallization tempera- of small crystallites. It has been reported that very small ture on heating suggests that crystallization is promoted rod-like crystallites are formed via a CO2 induced meso- in the PLLA/Hex compared with the reference bulk PLLA, phase, but no spherulites are formed (30). In this case, the and this might be due to the preexisting mesophase. crystallization of PLLA occurs very rapidly, and the crystallization behavior may be similar to that of the present precipitation-mediated system. 3.3 Morphology

We checked the crystalline morphology of the precipi- 3.4 Crystallization mechanism during tated PLLA samples via SEM, and found that no spheru- precipitation lites were formed. Figure 6 shows typical images observed for PLLA/MeOH. The rather random texture on a scale of The above results show that the alcohols tend to promote several tens of μm shown in the left panel of Figure 6 was the crystallization of PLLA during the precipitation from probably formed during the phase separation from the the chloroform solution. It may be reasonably understood M. Syazwan and T. Sasaki: Rapid crystallization and mesophase formation of PLLA during precipitation 335

Figure 6: SEM images for the PLLA/MeOH sample precipitated at 30°C.

Table 2: Cloud point for PLLA/chloroform/non-solvent system at 25°C with 5.0 wt% PLLA/chloroform solution.

Non-solvent Ra

MeOH 0.577 EtOH 0.625 nPrOH 0.803 2PrOH 0.863 Hex 0.471 aR = (mass of non-solvent)/(mass of PLLA/chloroform solution).

that the rates of mesophase formation and crystalliza- Figure 7: FTIR spectra in the range of 840–970 cm−1 for precipitated tion from a mobile phase of the PLLA/chloroform solu- PLLAs in methanol at different temperatures. tion are higher than that from the much less mobile phase of a bulk state, from which the crystallization process takes a much longer time. Also, the tendency of promot- and crystallization kinetics is not determined only by the ing crystallization is stronger for lower alcohols such as quench depth (and thus supercooling) into the bi-phase methanol. This suggests that the hydroxyl group of alco- region. hols plays a role in accelerating the crystallization. Rapid We found that the crystallization behavior depends crystallization has been reported to occur for blends of strongly on temperature of precipitation. Figure 7 shows PLLA/polyurethane during the formation of porous mate- the FTIR spectra for the samples precipitated in metha- rials under the presence of ethanol (41). Also, it has been nol at different temperatures. At 0°C and –41°C, no signs found that liquid alcohols induce the crystallization of a of crystallization were observed, even for PLLA/MeOH. bulk PLLA when it is immersed in methanol and ethanol Instead, a weak signal at 918 cm−1 is observed, which (10). These results suggest specific molecular interactions indicates formation of the mesophase. The temperature between PLLA and the hydroxyl group of alcohols, which dependence observed here suggests that the crystalli- might raise the mobility of PLLA chain. Table 2 shows zation rate is governed by the diffusion process in the the results of the cloud point measurements at 25°C. The present temperature range, i.e. the lower the mobility, the value R indicates the mass ratio of the non-solvent to the lower the crystallization rate. This is consistent with the PLLA/chloroform solution. As expected, n-hexane exhib- idea that the higher crystallization rate during precipita- its a lower value of R than alcohols, indicating its lower tion originates mainly from the high molecular mobility in compatibility with PLLA. However, the R value increases the liquid phase. as the number of carbons in the alcohol becomes high. In general, the precipitation phenomenon from a solu- This may be inconsistent with the observed crystallization tion in a non-solvent is considered to include both phase behaviors. The reason for this is unknown, but it is sug- separation and crystallization process, and the resulting gested that the interplay between the phase separation structure depends on the interplay between these two 336 M. Syazwan and T. Sasaki: Rapid crystallization and mesophase formation of PLLA during precipitation processes. The former process is essentially a liquid-liquid where the mobility of PLLA molecules is expected to be phase separation in a tri-component system, but actu- high enough for the crystallization. As for the PLLA/Hex, ally it may be regarded as a nearly solid-liquid separation crystallization does not occur, and just a mesophase is (PLLA-chloroform/methanol), because both PLLA/chloro- formed. In this case, repulsive interaction between PLLA form and chloroform/methanol are completely miscible. and n-hexane is rather strong, inducing a faster phase If the phase separation completed without crystallization, separation prior to crystallization. It is likely that the PLLA would not crystallize, because crystallization does hydroxyl group of alcohols raises the compatibility with not occur in a nearly bulk state at the precipitation tem- PLLA. Lower alcohols that have relatively high content perature that is below Tg. Thus it is likely that the crys- of hydroxyl group tend to suppress the phase separation tallization occurs in the liquid state before or during the rate, and as a result, promote crystallization. The low crys- phase separation process. Such a process may be regarded tallinity observed at lower temperatures suggests that the as crystallization at high supercoolings from a metastable present crystallization process is governed by the mobil- solution prior to or on the pathway to the phase sepa- ity of PLLA molecules. The rapid crystallization of PLLA ration. Considering the value of 5.0 wt% for the PLLA during precipitation revealed in this study is a remark- content of the initial solution, we assume that the phase able finding, which can contribute to the development of separation would occur from a metastable solution via process technology of bio-based polymer materials like nucleation and growth mechanism. 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