Formation Mechanism and Phase Transformation Behaviors of

Article pubs.acs.org/OPRD

Formation Mechanism and Phase Transformation Behaviors of Pantoprazole Sodium Heterosolvate Chen Jiang,† Yongli Wang,*,†,‡ Jiaqi Yan,† Jingxiang Yang,† Liping Xiao,† and Hongxun Hao*,†,‡ †

School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300072, China

‡

S Supporting Information *

ABSTRACT: In this paper, one new heterosolvate of pantoprazole sodium (PPS) was found, and its crystal structure was determined for the first time. It was found that both water molecules and acetone molecules get involved in the formation of crystal lattice of pantoprazole sodium heterosolvate. Powder X-ray diffraction (PXRD), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), Raman spectroscopy, and infrared spectroscopy (IR) were used to identify and characterize PPS heterosolvate. The phase transformation behaviors between PPS monohydrate and PPS heterosolvate were also investigated. It was found that PPS monohydrate can transform into PPS heterosolvate through either vapor sorption or solventmediated transformation. PPS heterosolvate can also transform into PPS monohydrate in the presence of hexane vapor or upon heating. Furthermore, the kinetics and mechanisms of desolvation of PPS heterosolvate were systematically investigated.

1. INTRODUCTION Pseudopolymorphism denotes systems where crystal structures of substances are defined by different unit cells which differ in their elemental compositions through the inclusion of one or more molecules of solvent.1−5 The term of pseudopolymorphism applies to hydrates or solvates. Hydrate, where water is the solvent, is the most common solvate.6,7 However, investigations on nonaqueous solvates become more and more important due to the increasing of quantity of organic compounds which can form solvates. Since solvent molecules are incorporated into the crystal lattice of solvates, solvates often exhibit different physical properties such as crystal morphology, solubility, melting point, and stability, which might affect the bioavailability and performance of the product.8,9 In order to control the formation of solvates, it is important to know their structures, their formation mechanisms, their possible phase transformation behaviors, and so on. Two types of phase transformation mechanisms have been proposed in literature.10,11 One is the solid state transformation which occur through molecular rearrangement or desolvation in a single phase. The other is solvent- or vapor-mediated transformation. Chakravarty et al.6 studied desolvation and vapor phase mediated transformation of thiamine hydrochloride methanol solvate. Marjo et al.12 found an acetone solvate of duloxetine hydrochloride and investigated its spontaneous desolvation at ambient temperature and atmosphere. Cui et al.13 studied phase transformation between form II and acetone solvate of candesartan cilexetil. They confirmed that form II can transform into acetone solvate in acetone, while acetone solvate can desolvate to form form II. But most solvates studied in the literature are homosolvates, in which just one kind of solvent molecules is involved in the formation of crystal lattice. Detoisien et al.14 found and characterized two heterosolvates of a hydrochlorate of API. Görbitz et al.15 listed some solvents which are prone to form heterosolvate. Liu et al.16 found cefodizime sodium heterosolvate, in which water © XXXX American Chemical Society

and ethanol are incorporated into the crystal lattice. However, no information about the formation mechanism and transformation of heterosolvate was reported. Pantoprazole sodium (CAS Registry No. 138786-67-1, hereinafter referred as PPS, Figure 1), a substituted

Figure 1. Chemical structure of PPS.

benzimidazole derivative, is an irreversible proton pump inhibitor. It is primarily used for the treatment of duodenal ulcers, gastric ulcers, and gastroesophageal reflux disease (GERD).17,18 PPS can exist in many crystalline forms, including hydrate forms (monohydrate, sesquihydrate), and solvate forms.17,19 No reports about the heterosolvate phenomenon, its crystal structure, and formation mechanism have been found. In this work, one new kind of heterosolvate of PPS is founded, and its crystal structure and formation mechanism was elucidated. To understand the formation mechanism and transformation behaviors of PPS heterosolvate, the main objectives of this work include: (1) developing the formation mechanism of PPS heterosolvate through crystal structure analysis and characterization and (2) investigating the phase transformation behaviors between PPS monohydrate and heterosolvate. In order to achieve these goals, a number of analytical techniques such as powder X-ray diffraction (PXRD), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), Received: July 29, 2015

A

DOI: 10.1021/acs.oprd.5b00243 Org. Process Res. Dev. XXXX, XXX, XXX−XXX

Organic Process Research & Development

Article

2.5. Solvent-Mediated Phase Transformation of PPS. The solvent-mediated transformation experiments from monohydrate to heterosolvate were carried out in a 100 mL cylindrical double-jacketed glass crystallizer whose temperature was controlled by a thermostatic bath. Certain amounts of PPS monohydrate were added into water and acetone mixture (xwater = 0.2) at 25 °C with the agitation speed of 200 r/min. The transformation process of monohydrate was in situ monitored by Raman spectroscopy. 2.6. Dynamic Vapor Sorption of PPS. The hexane desorption experiments of PPS heterosolvate were carried out by using a dynamic vapor sorption analyzer (VTI-SA, VTI Corporation, USA). The relative humidity (RH) was increased from 10% to 90% by steps of 10%. During each step, the RH was maintained until the mass change was less than 0.01 wt %/min or a maximum step time of 60 min. The measurements were carried out at 25 °C. The samples were analyzed by PXRD. 2.7. Solid-State Phase Transformation of PPS. The solid-state phase transformation behaviors of heterosolvate in temperature range of 25−170 °C was observed under hot stage microscope (HSM, Olympus UMAD3) at a heating rate of 5 °C/min. The isothermal desolvation kinetics were investigated by using TGA/DSC 1/500 in different temperature ranges from 40 to 60 °C and 105 to 120 °C by steps of 5 °C.

Raman spectroscopy, infrared spectroscopy (IR), dynamic vapor sorption (DVS), and hot stage microscopy (HSM) were used to analyze and characterize the samples.

2. EXPERIMENTAL SECTION 2.1. Materials. Deionized water and acetone were purchased from Tianjin Jiangtian Chemical Co. Ltd. in China. They are analytical reagents, and their mass fraction purities are higher than 99.5%. PPS monohydrate was provided by Hainan Lingkang Pharmaceutical Co., Ltd. without further purification, and its mass fraction purity is higher than 99.8%. PPS heterosolvate was prepared by solvent-mediated transformation of monohydrate. The two forms of PPS were characterized and confirmed by a series of analytical tools. 2.2. Determination of the Crystal Structure of PPS Heterosolvate. The single crystals of PPS heterosolvate were grown by using the solvent evaporation method. Certain amounts of PPS monohydrate were added into water and acetone mixture (xwater = 0.05) at 10 °C. Then, the suspension was filtered after reaching equilibrium. The filtrate was collected into a 10 mL beaker and sealed with plastic film. The beaker with solution was placed into an oven and kept at 20 °C. The solvent evaporated slowly, and crystals of PPS heterosolvate with appropriate size for single crystal X-ray diffraction were obtained after several days. The single crystal X-ray diffraction data of PPS heterosolvate were collected on a Rigaku-Rapid II diffractometer with Mercury2 CCD area-detector by using graphite-monochromatized Mo Kα radiation (λ = 0.71073 Å). 2.3. Characterization of PPS Monohydrate and Heterosolvate. The morphologies of monohydrate and heterosolvate of PPS were observed by polarized light microscope (PLM, Olympus BX51).The PXRD patterns of PPS monohydrate and heterosolvate were analyzed by Ridaku D/MAX 2500 in 2θ range from 2° to 50° with step size of 0.02°, voltage of 40 kV, and current of 100 mA. TGA was carried out by using TGA/DSC 1/500 (Mettler Toledo, Co., Switzerland) under protection of nitrogen (dry nitrogen; balance purge: 20 mL·min−1). The samples (5−10 mg) were placed into 70 μL pans, and the measurement temperature range was 25−170 °C with heating rate of 10 °C/min. DSC was performed by DSC 1/500 (Mettler Toledo, Co., Switzerland) under protection of nitrogen (dry nitrogen; balance purge: 50 mL·min−1). The samples (5−10 mg) were placed into 50 μL aluminum pans, and the temperature range together with the heating rate were the same with the TGA experiments. The Kaiser Raman RXN2 system (Kaiser Optical System, Inc. U.S.A) was equipped with both a PhAT probe head and a MR probe head. The PhAT probe head with noncontact optics was used to measure the powder Raman spectra of solid samples while the MR probe head with immersion optics was used to in situ monitor the transformation process of monohydrate. The excitation length and spectral resolution were 785 nm and 5 cm−1, respectively. The measurement duration was set at 1 min. Infrared spectra of monohydrate and heterosolvate were collected by using Nexus 670 infrared instrument (Thermo Inc.) with attenuated total reflectance accessories. 2.4. Exposure of PPS to Solvent Vapor. PPS monohydrate was exposed to solvent mixture vapor (water and acetone) for 60 min at 25 °C. Aliquots were withdrawn periodically and analyzed by PXRD.

3. RESULTS AND DISCUSSION 3.1. Crystal Structure of PPS Heterosolvate. The crystal structure of PPS heterosolvate was elucidated for the first time by using single crystal X-ray diffraction data. The crystallographic data of PPS heterosolvate are listed in Table 1. The Table 1. Crystallographic Data of PPS Heterosolvatea parameter

PPS heterosolvate

empirical formula formula weight (g/mol) crystal system space group a (Å) b (Å) c (Å) α (deg) β (deg) γ (deg) volume (Å3) density (g/cm3) Z Z′ Rint (%)

C19H24F2N3NaO7S 499.48 monoclinic P21/c 15.929(3) 10.828(2) 13.718(3) 90.00 91.62(3) 90.00 2365.12 1.292 4 0 5.9

a Z is the number of molecules in the unit cell. Z′ is the number of molecules in the asymmetric unit.

crystal structure is shown in Figure 2. The crystallographic information file is also given in Supporting Information. The single crystal structure of PPS heterosolvate shows that it is a monoclinic system with P21/c space group. From the structure, it can be seen that both acetone molecules and water molecules, which directly connect with sodium ion, are incorporated with PPS molecules. The acetone molecules are arranged along caxis and form an acetone channel in the interior of the crystal. Hydrogen bonds are formed between the oxygen atom (O5) of acetone and the hydrogen atom (HW2B) of water. The B



Article

Figure 2. Crystal structure of PPS heterosolvate: (a) the capped sticks plots; (b) the packing of unit cell. For clarity, hydrogen atoms are omitted.

consequent interactions between metal cation and the solvent molecules are so strong that the desolvation process of these bounded solvent molecules may undergo two steps. 3.2. Characterization of PPS Monohydrate and Heterosolvate. From the microscope images of monohydrate and heterosolvate of PPS shown in Figure 3, it can be seen that

Figure 5. TGA thermograms of monohydrate and heterosolvate of PPS.

water molecule and one acetone molecule in the lattice is 15.24%, while the theoretical content of another water molecule is 3.61%. It can be inferred that the first step weight loss corresponds to the removal of one water molecule and one acetone molecule, which is defined as “desolvation”. The second step weight loss corresponds to the removal of another water molecule, which is defined as “dehydration”. Figure 6 shows the DSC thermograms of monohydrate and heterosolvate of PPS. Table 2 gives the corresponding energies

Figure 3. Microscope images of monohydrate and heterosolvate of PPS.

monohydrate exhibits small plate-like morphology with low transparency, while heterosolvate exhibits prism morphology with high transparency. The PXRD patterns of PPS monohydrate and heterosolvate are shown in Figure 4. It can be found that both monohydrate and heterosolvate exhibit distinct peaks, and the simulated results are consistent with the experimental results.

Figure 6. DSC thermograms of monohydrate and heterosolvate of PPS.

associated with the peaks in Figure 6. PPS monohydrate shows only one endothermic peak when water is removed. But PPS heterosolvate shows two endothermic peaks, and the second endothermic peak is very close to the peak of monohydrate, which means that monohydrate is obtained after the first step removal of solvent. Therefore, the desolvation energy for Table 2. Thermal Analysis Data of Monohydrate and Heterosolvate of PPS

Figure 4. PXRD patterns of monohydrate and heterosolvate of PPS.

compound

From the TG thermograms of PPS monohydrate and heterosolvate shown in Figure 5, it can be seen that the weight loss of monohydrate was 4.04%, which is consistent with the theoretical water content (4.26%). However, heterosolvate shows two weight loss steps, corresponding to twice solvent release. The weight loss is 15.00% in the first step and 2.65% in the second step. Interestingly, the theoretical content of one

first peak temperature (°C) second peak temperature (°C) ΔHexp des of desolvation (J/g sample) ΔHexp deh of dehydration (J/g sample) xsolvent ΔHcal deh for dehydration (J/g) C

monohydrate 153.8 128.23 128.23

Heterosolvate 85.3 154.1 184.13 108.06 0.1500 127.13



Article

heterosolvate in Table 2 is the energy for releasing one water molecule plus one acetone molecule, while the dehydration energy for heterosolvate is the energy for releasing another water molecule. It is expected that the enthalpies of dehydration of monohydrate and heterosolvate should be the same since the dehydration peaks are consistent. However, the experimental enthalpies of dehydration shown in Table 2 are based on the initial sample mass, which includes all solvents. These values can be converted to energy per unit mass of the monohydrate as follows:20 cal ΔHdeh =

exp ΔHdeh 1 − xsolvent

(1)

where ΔHexp deh is the experimental enthalpy of dehydration per unit initial sample mass estimated by DSC, ΔHcal deh is the calculated enthalpy of dehydration per unit monohydrate mass, and xsolvent is the value of first step weight loss obtained directly from TGA. Obviously, the calculated enthalpies of dehydration for monohydrate and heterosolvate are quite similar, which indicate again that the product from desolvation of heterosolvate has the same structure with monohydrate. In order to verify the TGA and DSC results, PXRD data of samples at different stages of the thermal treatments were also collected. The results confirm that heterosolvate has transformed into monohydrate after the first step desolvation. Consequently, it can be confirmed that the first step for desolvation is the removal of acetone molecule and water molecule attached to acetone molecule by hydrogen bond, and the second step is the removal of another water molecule. This can also be verified by the crystal structure of PPS heterosolvate. Since acetone molecules with low boiling points form channels and connect with water molecules by hydrogen bonds in the lattice, the desolvation begins at low temperature, and water molecules are removed together with acetone molecules. Another water molecule is removed subsequently, which is the same with monohydrate. The Raman spectra of solid state forms of PPS are shown in Figure 7a. It can be found that there are some differences in the Raman spectra of these two forms, such as the characteristic peaks at 1244 cm−1 for monohydrate and 1265 cm−1 for heterosolvate. The Raman spectra in Figure 7b were obtained when monohydrate and heterosolvate were added into the binary solvent mixture of water and acetone, respectively. By comparison of Figure 7a and b, the peaks at 1244 cm−1 for monohydrate and 1265 cm−1 for heterosolvate were selected as characteristic peaks to monitor the transformation process. The FTIR spectra of solid state forms of PPS are shown in Figure 8. Since acetone is embedded into the crystal lattice of heterosolvate, there are obvious differences in the spectra of the two forms. In the spectra of heterosolvate, there is a stretching vibration peak of carbonyl group (CO) at 1696 cm−1 which does not exist in the spectra of monohydrate. When compared with the stretching vibration peak of CO in acetone at 1715 cm−1, it can be found that the stretching vibration peak of heterosolvate occur redshift to 1696 cm−1, which can be attributed to hydrogen bond interaction between the CO and the water molecular in the crystal lattice. 3.3. Phase Transformation from Monohydrate to Heterosolvate of PPS. Phase transformation behaviors from monohydrate to heterosolvate of PPS were investigated in solvent vapor or solution. Figure 9 shows the changes of PXRD patterns for PPS monohydrate when it is exposed to the vapor

Figure 7. Raman spectra of monohydrate and heterosolvate of PPS: (a) Raman spectra obtained from solid powders; (b) Raman spectra obtained from solution.

Figure 8. FTIR spectra of solid state monohydrate and heterosolvate of PPS.

of mixture of water and acetone. It can be seen that the characteristic peaks of monohydrate at 2θ of 5.3° and 13.1° became lower, while the characteristic peaks of heterosolvate at 2θ of 5.6° and 26.1° started to appear after 20 min. Then both characteristic peaks of monohydrate and heterosolvate can be observed in the next 40 min, which indicates that both of the two forms existed during this period. But after 60 min, only characteristic peaks of heterosolvate can be observed, which indicates that PPS monohydrate has completely transformed D



Article

Figure 11. DVS profiles of PPS heterosolvate.

Figure 9. PXRD patterns of PPS monohydrate after exposure to vapor of solvent mixture.

beginning of the experiment, and the weight gradually decreased with the increasing of RH until it reached maximum and kept constant at RH = 90%. The weight loss of sample is around 13.66%, which is consistent with the stoichiometric value (15.24%) of one water molecule and one acetone molecule. The sample obtained from desolvation in DVS is further confirmed to be monohydrate by PXRD data (Figure 12). This can be explained by the hydrogen bonding

into heterosolvate through exposure to the vapor of mixture of water and acetone. The solvent-mediated phase transformation from monohydrate to heterosolvate of PPS was in situ monitored by using Raman spectroscopy. The results are shown in Figure 10. After

Figure 10. Changes of Raman relative intensity during the solventmediated transformation from monosolvate to heterosolvate of PPS in solution. Figure 12. PXRD patterns after vapor sorption and desolvation of PPS heterosolvate.

addition of the monohydrate, the intensity of monohydrate characterization peak (1244 cm−1) increased dramatically to the highest. Then, it decreased gradually in the following 35 min, which was caused by the dissolution of monohydrate. Meanwhile, the intensity of heterosolvate characterization peak (1265 cm−1) increased gradually, which indicated the nucleation and growth of heterosolvate. The intensities of Raman peaks of monohydrate and heterosolvate kept steady when the transformation was completed. The results obtained from the Raman data reveal that the monohydrate form can transformation into heterosolvate form in water and acetone binary solvent mixtures, and the solvent-mediated transformation is controlled by the dissolution of monohydrate and the nucleation and growth of heterosolvate.21 3.4. Phase Transformation from Heterosolvate to Monohydrate of PPS. The isothermal desorption behaviors of PPS heterosolvate in hexane vapor were investigated by DVS at 25 °C. The results are shown in Figure 11. From hexane vapor desorption profiles, purge gas of hexane can accelerate the escape of acetone molecule and water molecule from the crystal lattice. PPS heterosolvate began to lose weight from the

environment of the solvent molecule in the lattice.6 In the lattice, the acetone molecule is linked to PPS molecule by a single hydrogen bond with water molecule. As a result, they can be readily removed from the lattice, resulting in the poor physical stability of PPS heterosolvate in hexane vapor. It has been suggested that the affinity of the solvent in the vapor phase with the solvent in the lattice will determine the ease of desolvation.22 The solid-state phase transformation from heterosolvate to monohydrate of PPS was observed by using HSM. Figure 13 shows the changes of the morphology during desolvation and dehydration. It can be seen that the removal of water and acetone led to the declining of the crystal transparency with the increasing of temperature. Meanwhile, some breakages can be observed in the crystal surface. When water and acetone were removed completely, the crystals became almost opaque. Then the crystal began to dehydrate, and the transparency increased along with fusion. Based on the classification for “water evolution type” (WET) dehydrations proposed by Galwey,23 E



Article

with the increasing of temperature. In order to determine the mechanisms and kinetics of PPS desolvations, various solid state reaction kinetic models were employed to derive the transition rate (Table 3).24−26 By fitting the experiment data in Table 3. Kinetic Equations and Mechanisms of Solid State Reactions model A2 A3

Figure 13. Hot stage microscopy images during PPS heterosolvate desolvation.

A4 P1

the dehydration of heterosolvate belongs to WET 6 type. The crystal forms during desolvation and dehydration were determined by PXRD pattern (Figure 12). The results revealed that PPS heterosolvate can transform into monohydrate with the increasing of temperature. The breakages on the crystal surface can be explained by the removal of solvent molecules. To better understand the solid-state transformation of PPS heterosolvate, the kinetics of the transformation were investigated under isothermal conditions. Figure 14 and Figure

D1 D2 D3 D4

R1 R2 R3

F1 F2 F3

equation, g(α) = kt

mechanism

Nucleation Models [−ln(1 − α)]1/2 one-dimensional nuclei growth (Avrami-Erofeev equation, n = 2) [−ln(1 − α)]1/3 two-dimensional nuclei growth (Avrami-Erofeev equation, n = 3) [−ln(1 − α)]1/4 three-dimensional nuclei growth (Avrami-Erofeev equation, n = 4) ln[α/(1 − α)] random nucleation (Prout-Tompkins equation) Diffusion Models α2 one-dimensional diffusion ((1 − α) ln(1 − α)) + α two-dimensional diffusion (1 − (1 − α)1/3)2 three-dimensional diffusion (Jander equation) 1 − (2/3)α − (1 − α)2/3 three-dimensional diffusion (GinstlingBrounshtein equation) Phase Boundary Reaction Models α one-dimensional phase boundary reaction 1 − (1 − α)1/2 two-dimensional phase boundary reaction (contracting cylinder) 1 − (1 − α)1/3 three-dimensional phase boundary reaction (contracting sphere) Reaction-Order Models −ln(1 − α) first-order reaction 1/(1 − α) − 1 second-order reaction (1/2)[(1 − α)−2 − 1] third-order reaction

the range of 5−95 wt % to the equations g(α), a linear relationship is fitted between g(α) and transition time t. The corresponding slopes give the transition rate constant (k) at different temperatures. Coefficients of determination (R2) for different kinetic models were tabulated in Table 4 and Table 5. The results demonstrate that some models, particularly phase boundary reaction models (R2, R3), fairly fit the experimental data. For phase boundary reaction models, nucleation is assumed to be instantaneous throughout the surface, and the

Figure 14. Representative isothermal desolvation progress curves of PPS heterosolvate.

15 present the transition profiles from 40 to 60 °C and 105 to 120 °C, respectively. Obviously, the transform rates increase

Table 4. Coefficients of Determination (R2) for Different Kinetic Models during Desolvationa R2

Figure 15. Representative isothermal dehydration progress curves of PPS heterosolvate.

a

F

model

40 °C

45 °C

50 °C

55 °C

60 °C

A2 A3 P1 D1 D2 D3 D4 R1 R2 R3 F1 F2

0.854 0.149 0.527 0.970 0.921 0.815 0.889 0.907 0.999 0.996 0.947 0.619

0.864 0.232 0.576 0.970 0.944 0.864 0.922 0.867 0.989 0.997 0.970 0.691

0.896 0.323 0.539 0.963 0.927 0.838 0.901 0.906 0.996 0.996 0.956 0.661

0.912 0.370 0.505 0.955 0.908 0.810 0.878 0.934 0.998 0.991 0.940 0.631

0.901 0.321 0.526 0.959 0.914 0.817 0.885 0.922 0.994 0.998 0.945 0.636

The models fitted not well are omitted. DOI: 10.1021/acs.oprd.5b00243 Org. Process Res. Dev. XXXX, XXX, XXX−XXX


Article

Table 5. Coefficients of Determination (R2) for Different Kinetic Models during Desolvationa R2

a

model

105 °C

110 °C

115 °C

120 °C

A2 P1 D1 D2 D3 D4 R1 R2 R3 F1 F2

0.622 0.633 0.991 0.978 0.893 0.956 0.712 0.947 0.980 0.983 0.684

0.826 0.531 0.972 0.920 0.813 0.888 0.899 0.997 0.995 0.946 0.617

0.882 0.715 0.971 0.888 0.736 0.838 0.653 0.998 0.990 0.898 0.515

0.754 0.687 0.973 0.971 0.911 0.957 0.725 0.955 0.987 0.990 0.752

Figure 16. Desolvation and dehydration model with hydrogen atoms omitted. The gray circles represent carbon atoms, the red circles represent oxygen atoms, the purple circles represent sodium atoms, and the blue shaded parts show acetone channels in the heterosolvate.

The models fitted not well are omitted.

rate-controlling step is the progress of the product layer from the surface of the crystal inward and is different for various crystal morphologies.13,25 Consequently, based on statistics, the favored model is three-dimensional phase boundary reaction (R3). The rate-controlling step of phase boundary reaction is the dissociation of acetone and water molecules from the crystal lattice. The temperature dependence of the rate constants based on the R3 model can be evaluated by the Arrhenius equation:

⎛ E ⎞ k = A exp⎜ − a ⎟ ⎝ RT ⎠

4. CONCLUSIONS In this work, one new heterosolvate of PPS was found and its crystal structure was determined. It was found that both water and acetone molecules participate in the formation of crystal lattice of PPS heterosolvate. The phase transformation behaviors between PPS monohydrate and heterosolvate were also investigated. The results indicated that PPS monohydrate can transform into heterosolvate through vapor sorption and solvent-mediated transformation. Also, PPS heterosolvate can also transform into monohydrate in the presence of hexane vapor or upon heating. The kinetics of transformation were systematically investigated at different temperatures. The transformation process can be explained by three-dimensional phase boundary reaction. The phase transformations between PPS monohydrate and heterosolvate are summarized as follows.

(2)

where Ea is activation energy, R is gas constant, and T is absolute temperature. Table 6 gives the results of the activation Table 6. Activation Energy for Desolvation and Dehydration solvent release

model

T (°C)

k (min−1)

Arrhenius plot Ea (kJ/mol)

desolvation

R3

R3

0.00535 0.02248 0.03845 0.05660 0.08482 0.00551 0.01006 0.03310 0.05426

112.47

dehydration

40 45 50 55 60 105 110 115 120

■

199.11

ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.oprd.5b00243. X-ray crystallographic information files (CIF) for structure of PPS heterosolvate (CIF)

■

energy analyses. The activation energy for removal of another water is larger than the activation energy for removal of water and acetone from heterosolvate. According to the above analysis, the desolvation and dehydration model is described visually in Figure 16. In this Figure 16, acetone molecules were drawn to show the acetone channels in the heterosolvate. The removal of acetone and water from heterosolvate can happen at lower desolvation temperature and lower activation energy because the existence of channels in the heterosolvate will facilitate the desolvation. The removal of another water has comparatively higher dehydration temperature due to the strong metal−water interactions. According to this model, the acetone channels, hydrogen bonds, and metal−water interactions are responsible for the desolvation and dehydration.

AUTHOR INFORMATION

Corresponding Authors

*Tel.: +86-22-27405754; fax: +86-22-27374971. E-mail address: [email protected]. *E-mail address: [email protected]. Notes

The authors declare no competing financial interest.

■

ACKNOWLEDGMENTS The authors are very thankful to National Natural Science Foundation of China (No. 21376165) and Program of International S&T Cooperation from Ministry of Science and Technology of the People’s Republic of China (No. 2013DFE43150) for the financial support. G



■

Article

REFERENCES

(1) Chang, H.-C.; Jiang, J.-C.; Chao, M.-C.; Lin, M.-S.; Lin, S. H.; Chen, H.-Y.; Hsueh, H.-C. J. Chem. Phys. 2001, 115, 8032. (2) Mizuno, K.; Imafuji, S.; Ochi, T.; Ohta, T.; Maeda, S. J. Phys. Chem. B 2000, 104, 11001. (3) Brittain, H. G. J. Pharm. Sci. 2012, 101, 464. (4) Bechtloff, B.; Nordhoff, S.; Ulrich, J. Cryst. Res. Technol. 2001, 36, 1315. (5) Chieng, N.; Rades, T.; Aaltonen, J. J. Pharm. Biomed. Anal. 2011, 55, 618. (6) Chakravarty, P.; Suryanarayanan, R. Cryst. Growth Des. 2010, 10, 4414. (7) Singh, D.; Baruah, J. B. Cryst. Growth Des. 2011, 11, 768. (8) Ferrari, E. S.; Davey, R. J.; Cross, W. I.; Gillon, A. L.; Towler, C. S. Cryst. Growth Des. 2003, 3, 53. (9) Nangia, A. Cryst. Growth Des. 2006, 6, 2. (10) Du, W.; Yin, Q.; Hao, H.; Bao, Y.; Zhang, X.; Huang, J.; Li, X.; Xie, C.; Gong, J. Ind. Eng. Chem. Res. 2014, 53, 5652. (11) Zhang, X.; Yin, Q.; Du, W.; Gong, J.; Bao, Y.; Zhang, M.; Hou, B.; Hao, H. Ind. Eng. Chem. Res. 2015, 54, 3438. (12) Marjo, C. E.; Bhadbhade, M.; Hook, J. M.; Rich, A. M. Mol. Pharmaceutics 2011, 8, 2454. (13) Cui, P.; Yin, Q.; Guo, Y.; Gong, J. Ind. Eng. Chem. Res. 2012, 51, 12910. (14) Detoisien, T.; Arnoux, M.; Taulelle, P.; Colson, D.; Klein, J. P.; Veesler, S. Int. J. Pharm. 2011, 403, 29. (15) Görbitz, C. H.; Hersleth, H.-P. Acta Crystallogr., Sect. B: Struct. Sci. 2000, 56, 526. (16) Liu, Z.; Yin, Q.; Zhang, X.; Gong, J.; Xie, C. Ind. Eng. Chem. Res. 2014, 53, 3373. (17) Zupančič, V.; Ograjšek, N.; Kotar-Jordan, B.; Vrečer, F. Int. J. Pharm. 2005, 291, 59. (18) Reddy, M. S.; Eswaraiah, S.; Mathad, V. T.; Anilkumar, P.; Chandrashekar, E. R. R.; Shanmugam, G. Process for preparation of crystalline form-1 of pantoprazole sodium sesquihydrate. U.S. Patent 2004/0186139 A1, 2005. (19) Allegrini, P.; Ventimiglia, G.; Sommei, A.; Castaldi, G. Polymorphs of pantoprazole sodium salt and process for the preparation thereof. U.S. Patent 2005/0245578 Al, 2005. (20) Kim, Y.-s.; Rousseau, R. W. Cryst. Growth Des. 2004, 4, 1211. (21) O’Mahony, M. A.; Maher, A.; Croker, D. M.; Rasmuson, Å. C.; Hodnett, B. K. Cryst. Growth Des. 2012, 12, 1925. (22) Fujii, K.; Ashida, Y.; Uekusa, H.; Hirano, S.; Toyota, S.; Toda, F.; Pan, Z.; Harris, K. D. Cryst. Growth Des. 2009, 9, 1201. (23) Galwey, A. K. Thermochim. Acta 2000, 355, 181. (24) Koradia, V.; de Diego, H. L.; Elema, M. R.; Rantanen, J. J. Pharm. Sci. 2010, 99, 3966. (25) Alkhamis, K. A.; Salem, M. S.; Obaidat, R. M. J. Pharm. Sci. 2006, 95, 859. (26) Yang, X.; Wang, X.; Ching, C. B. J. Raman Spectrosc. 2009, 40, 870.

H


Formation Mechanism and Phase Transformation Behaviors of

Recommend Documents