Preparation and Dehydration Kinetics of Complex Sulfadiazine

Subscriber access provided by Flinders University Library

Full Paper

Preparation and Dehydration Kinetics of Complex Sulfadiazine Calcium Hydrate with Both Channel-type and Coordinated Water Jia Sun, Chuang Xie, Xia Zhang, Ying Bao, Baohong Hou, Zhao Wang, Junbo Gong, Hongxun Hao, Yongli Wang, Jingkang Wang, and Qiuxiang Yin Org. Process Res. Dev., Just Accepted Manuscript • DOI: 10.1021/acs.oprd.6b00027 • Publication Date (Web): 28 Mar 2016 Downloaded from http://pubs.acs.org on March 29, 2016

Just Accepted “Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted online prior to technical editing, formatting for publication and author proofing. The American Chemical Society provides “Just Accepted” as a free service to the research community to expedite the dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully peer reviewed, but should not be considered the official version of record. They are accessible to all readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or consequences arising from the use of information contained in these “Just Accepted” manuscripts.

Organic Process Research & Development is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Published by American Chemical Society. Copyright © American Chemical Society. However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties.

Page 1 of 23

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Organic Process Research & Development

Preparation and Dehydration Kinetics of Complex Sulfadiazine Calcium Hydrate with Both Channel-type and Coordinated Water Jia Sun†, Chuang Xie†, ‡, Xia Zhang†, Ying Bao†, ‡, Baohong Hou†, ‡, Zhao Wang†, ‡, Junbo Gong†, ‡, Hongxun Hao†, ‡, Yongli Wang †, ‡, Jingkang Wang †, ‡, Qiuxiang Yin†, ‡,*

†

School of Chemical Engineering and Technology, State Key Laboratory of Chemical

Engineering, Tianjin University, Tianjin 300072, People’s Republic of China ‡

Collaborative Innovation Center of Chemical Science and Chemical Engineering,

Tianjin 300072, People’s Republic of China

1

ACS Paragon Plus Environment


1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Table of Contents Graphic:

2


Page 2 of 23

Page 3 of 23

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


ABSTRACT: A new hydrate of sulfadiazine calcium (Hydrate I) was discovered and the crystal structure was determined using single crystal X-ray diffraction. Both channel-type water (9.23 wt%) and calcium-ion coordinated water (11.87 wt%) existed in the unit cell. The thermal stability and dehydration of Hydrate I were investigated by thermal gravimetric analysis, hot stage microscopy, powder X-ray diffraction, Fourier transform infrared spectroscopy, and scanning electron microscopy. A two-step dehydration process was detected from Hydrate I to anhydrous phase (AP) with the intermediate of the less-hydrated form (Hydrate II). The dehydration kinetics of Hydrate I with both channel-type and coordinated water was studied using model fitting method and model free method in isothermal mode. The dehydration activation energy was derived via Friedman method. Further, the 1st-step dehydration of Hydrated I was determined to be 2D phase boundary reaction mechanism and the 2nd-step dehydration was found to be 3D phase boundary reaction mechanism via model fitting approach. Keywords: sulfadiazine calcium, hydrate, dehydration kinetics

3



1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

INTRODUCTION The formation of solvates is one of the most common phenomenon in the process of crystallization.1, 2 Hydrate, as a special kind of solvate with water as solvent3, 4, is of great importance in the pharmaceutical field considering almost one-third of active pharmaceutical ingredients (API) can form hydrates.5, 6 According to the states of water in the crystal lattice, hydrates have been structurally divided into three categories including isolated site hydrates, channel hydrates, and ion associated hydrates.7-10 Molecules of water incorporated into the crystal lattice of the solvate play an important role in alternating and stabilizing the crystal structure and consequently change the solubility, stability, and bioavailability of the APIs.9 On the other hand, the loss of the enclosed water (i.e. dehydration) happens in drying, tableting, storage, and transportation can lead to different hydration states with varied processibility, physicochemical properties, product performance and shelf-life.1, 9-12 Therefore, it is important to study the hydrated states, the interaction between water and solute in the dehydration process as well as the dehydration kinetics of drug product. The thermal dehydration of a hydrate is usually treated as a solid state reaction to get a deep understanding of the process. Solid kinetics models are mathematical description of solid state reaction. Therefore, essentially, the mechanism of dehydration process is mathematical description of solid state reaction. Models are often classified based on mechanistic assumptions, including nucleation, geometrical concentration, diffusion, or reaction-order.13-15 Dehydration kinetic model and dehydration activation energy are important and can help to a better understanding of the dehydration mechanism.11 The kinetic model for a dehydration process can be determined via model fitting method5, 16. The corresponding model mechanism and average activation energy of the overall dehydration process could be obtained simultaneously. While the conversion-dependent activation energy could be 4


Page 4 of 23

Page 5 of 23

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


obtained via model free method16, 17 such as the Friedman method5, 18 to provide more detailed information in different stages of the dehydration process. Sulfadiazine is an important member of the large family of sulfonamides.19, 20 It exhibits many advantages as an antibacterial drug, such as broad antimicrobial spectrum, chemical stability, low price and low toxicity. Sulfadiazine calcium (SC) is the important intermediate product when refining crude sulfadiazine, which can be obtained by the reaction of calcium hydroxide with sulfadiazine according to the equation shown in Figure 1. But its solid form has seldom been separated from aqueous solution. An unreported hydrate of SC containing two types of water was produced by means of cooling crystallization in this work. Such hydrate with different types of water in the crystal structure is existing, but it is not so common in the family of hydrates.8 More types of interactions and the possible interconversion between different types of water would make the dehydration process more complicated. The dehydration of a hydrate which contains different types of water simultaneously isn’t sufficiently reported. The objectives of this study can be listed as follows: (1) characterizing the hydrate of SC (Hydrate I) and dehydrated SC (Hydrate II and anhydrous phase AP), (2) studying the two-step dehydration kinetics of Hydrate I. The results of this study may give useful support to understand the desolvation of other solvates containing different types of solvent in one crystal structure.

EXPERIMENT SECTION 2.1 Materials. Sulfadiazine (99wt%) was provided by PKU HealthCare Corp., Ltd. Deionized water of high performance liquid chromatography grade was used. Calcium oxide (98+wt%) was purchased from Tianjin Beifang Tianyi chemical reagent factory. 5



1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

2.2 Preparation of Hydrate I, Hydrate II and AP of SC. As shown in Figure 1, SC was prepared by the reaction of calcium hydroxide with sulfadiazine at 353.15 K for 1 h. Calcium hydroxide was obtained by adding calcium oxide to water in our lab. Then Hydrate I will crystallize out by cooling the solution to 283.15 K with a constant cooling rate of 10 K/min in 7 h. Single crystal of Hydrate I was cultivated by slow evaporation of solvent in a 10 ml beaker covered with perforated plastic film at room temperature. Hydrate II and AP were obtained by heating Hydrate I to 363.15 K and 453.15 K, respectively. 2.3 X-ray diffraction. The single crystal X-ray diffraction of Hydrate I was carried out on a single crystal X-ray diffractometer (SXRD, R-AXIS-RAPID II, Rigaku) using Mo Kα radiation source (λ=0.7103 Å). Powder X-ray diffraction (PXRD) data of Hydrate I, Hydrate II, and AP between 5 to 45 ° with a step size of 0.02 ° was collected on a powder X-ray diffractometer (PXRD, D/MAX 2500, Rigaku) using Cu Kα radiation, operating at a voltage of 40 kV. The PXRD patterns during the solid-solid transformation process form Hydrate I to AP were monitored offline by sampling at different heating temperatures. 2.4 Thermal analysis Samples of Hydrate I (5-10 mg) were heated from 298.15 K to 473.15 K at a rate of 10 K/min, and the thermal gravimetric was performed with thermal gravimetric analyzer (TGA/DSC, 1/SF, Mettler Toledo). 2.5 Fourier transform infrared spectroscopy. Infrared spectra of Hydrate I, Hydrate II and AP were recorded on Fourier transform infrared spectrometer (FTIR, TENSOR27, Bruker) with 4 cm-1 resolution. The scanning range was limited to 4000-400 cm-1. 6


Page 6 of 23

Page 7 of 23

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


2.6 Morphology investigation. The morphology of Hydrate I, Hydrate II, and AP during the dehydration process was monitored both in situ using a hot stage microscopy (HSM, UMAD3, Olympus) and offline with a scanning electron microscope (SEM, X650, Hitachi). 2.7 Dehydrated kinetics analysis. The two-step dehydration kinetics of Hydrate I was studied in isothermal mode18, 21 with the aid of TGA. In isothermal mode, the heater unit was preset to the target temperature before the insertion of the sample. The Hydrate I samples were heated at the temperatures of 318.15, 323.15, 328.15, and 333.15 K while Hydrate II was studied at 363.15, 368.15, 373.15, and 378.15 K. The terminal of dehydration was judged when the sample weight was constant. The product of each step dehydration was confirmed by PXRD.

RESULTS AND DISCUSSION 3.1 Crystal structure and thermal property of Hydrate I. The crystal structure of Hydrate I was resolved via SXRD and the crystallographic information is listed in Table 1. The small R indices suggest that the resolved crystal structure is reliable. From Figure 2a, it can be seen that there are two sorts of water existing in the unit cell. One is directly connected with calcium ion, the other is not associated to calcium ion and it is arranged along the a-axis (Figure 2b). According to the definition proposed by Morris KR in 1993,7 hydrates have been structurally divided into isolated site hydrates, channel hydrates, and ion associated hydrates. In isolated site hydrates, water molecules are isolated from direct contact with each other by solute molecules. Channel hydrates contain chains, planes, or networks of water molecules through the crystal structure. Ion associated hydrates involve strong metal-ion coordinated to water molecules. Therefore, two sorts of water in Hydrate I of SC can be 7



1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

classified as calcium-ion coordinated water and channel-type water. The total number of water molecules in the Hydrate I of SC is 16, including 7 channel-type water molecules and 9 calcium-ion coordinated water molecules. Calculation by the result of SXRD, the total content of water in unit cell is 21.10% in mass fraction, including 9.23% channel-type water and 11.87% calcium-ion coordinated water. The thermal behavior of Hydrate I was investigated using TGA and DSC. Two endothermic peaks appear at about 358.15 K and 433.15 K on the DSC curve (Figure 3, curve b). The uncertainties of temperatures are u(T)=0.01 K. The corresponding weight losses from the TGA curve (Figure 3, curve a) indicate a two-step dehydration process of Hydrate I during the decomposition. From TGA data, the weight losses due to the dehydration were 9.47% for the 1st-step and 11.78% for the 2nd-step, which are very close to the data in the crystal cell (9.23% and 11.87%). The uncertainties of weight losses are u(water content)=0.01%. It is indicated that the 1st-step dehydration was occurred during 313.15 K to 363.15 K, the low dehydration temperature and wide dehydration temperature ranges accord with the thermal feature of channel hydrates dehydration. The 2nd-step dehydration takes place from 368.15 to 453.15 K, the high dehydration temperature attributed to strong metal-ion coordinated to water. The above classification of two sorts of water is proved to be right by TGA and DSC. The two-step dehydration process indicates that the channel-type water was eliminated in the 1st-step, leading to a less-hydrated form (Hydrate II), and the calcium-ion coordinated water escaped in the 2nd-step, forming the anhydrous phase (AP) of SC.

3.2 Solid-solid transformation from Hydrate I The solid transformation of Hydrate I in the dehydration process was monitored both online using HSM and offline using SEM. During the dehydration process, the surface of the crystals became opaque and coarse with unchanged shape (see Figure S1 in 8


Page 8 of 23

Page 9 of 23

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


Supporting Information). Cracks in the solid of Hydrate II (Figure 4b) imply that the loss of channel-type water can cause the collapse of the crystal lattice. Despite the shape of the crystals were kept during the dehydration of channel-type water, no single crystal of Hydrate II was obtained due to the collapse of the crystal structure. Hydrate II and AP obtained from the dehydration process were collected and checked using PXRD. In comparison to Hydrate I, the PXRD pattern of Hydrate II (Figure 5a) shows new peaks at 7.68, 10.18, 13.32, 14.92, 16.8, 20.4, 21.46 ° and peaks disappear at 8.42, 10.56, 11.16, 12.7, 14.38, 18.08, 22.2, 23.28°, which verifies that the dehydration of channel-type water in the 1st-step dehydration process leads to the collapse of crystal lattice of Hydrate I and the reorganization to Hydrate II. After the 2nd-step of dehydration, the PXRD pattern of AP solid exhibited only one broad peak at 7.68 °, suggesting that the elimination of calcium-ion coordinated water causes the complete collapse of the crystal structure and results in amorphous SC. The changes of PXRD patterns during the dehydration process in Figure 5b indicates that the solid-solid transformation from Hydrate I to AP takes place. Therefore, the 1st-step dehydration process can be classified as cooperative release of water molecules followed by the cooperative reorganization, which belongs to the class II-Coop.-Reorg., while the 2nd-step dehydration process can be classified as destructive dehydration departure of water molecules generates amorphous SC, belonging to the class I-Destr.-Disorg., according to the dehydration system described by Samuel petit.22 The eliminating of two types of water can also be verified by using IR (Figure S2, Supporting information). The shrink of the broad peak of Hydrate I represents the dehydration of channel-type water; the disappearance of peak at 3641 cm-1 and peak shifts around 3100-3500 cm-1 indicate the miss of calcium-ion coordinated water and the related hydrogen bond to –NH2 and –NH- functional groups (Table S1, Supporting information). 9



1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 10 of 23

3.3 Dehydration kinetics of Hydrate I. In isothermal mode, the dehydration process of Hydrate I was monitored and the dehydration fraction, α, was recorded in Figure 6. The isothermal dehydration curves in Figure 6 indicate that dehydration rates decrease with the reaction progress. The dehydration fraction α can be calculated by equation (1):5

m −m α= i a

(1)

mi − m f

where mi, ma, and mf are the initial mass (t=0), the actual sample mass at time t and the final sample mass, respectively. 3.3.1 Model fitting analysis The process of dehydration kinetics can be described by equation (2):23

dα =k T f α dt

( ) ( )

(2)

where t is time, k(T) is the rate constant, f(α) is the differential form of the reaction model. The rate constant k(T) can be considered to follow an Arrhenius equation:24

( )

k T = A exp

−E RT

(3)

where A is the pre-exponential factor (min-1), E is the activation energy (kJ·mol-1), R is the gas constant (8.314 J·K-1·mol-1), T is the absolute temperature (K). Considering the temperature kept constant in the isothermal mode, the integral form of reaction model, g(α), can be described by equation (4): 25

10


Page 11 of 23

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


α

t dα g α = ∫ = ∫ k ( T )dt 0 f (α ) 0

( )

(4)

Thus, the plot of g(α) vs. time presents to be a straight line with slope equals to k(T). Various dehydration kinetic models13, 21 (Table S2, Supporting information) were tested in order to achieve a good match to the experimental data using model fitting method. The regression results are listed in detail in Table S3-S4 (see Supporting Information). In the tested models, (R2) model was found to agree with the experimental data best for the 1st-step dehydration of Hydrate I, while (R3) model is most suitable for the 2nd-step dehydration. Isothermal dehydration at different temperatures can give a temperature-dependent rate constants k(T) based on the selected R2 model and R3 model. By using the temperature-dependent rate constant data, the average activation energy, E, can be obtained based on the Arrhenius analysis according to Equation (3). The corresponding dehydration activation energies for the 1st-step dehydration and 2nd-step dehydration are 114.9 kJ·mol-1 and 82.2 kJ·mol-1, respectively. By model fitting analysis, the energy required for the 1st-step dehydration (114.9 kJ·mol-1) is more than that for the 2nd-step dehydration (82.2 kJ·mol-1). According to the result of solid-solid transformation in section 3.2, it can be known that the energy for the 1st-step dehydration involves the energy necessary for release of channel-type water and the reorganization energy, while the energy for the 2nd-step dehydration involves the energy necessary for release of calcium-ion coordinated water only. Therefore, this unusual phenomena may attributed to the structure reorganization to Hydrate II in the 1st-step dehydration. Noteworthily, the above activation energies are the average values over the entire reaction process. A conversion-dependent analysis is needed to provide more information (see section 3.3.2) 11



1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 12 of 23

3.3.2 Model free analysis. The advantage of model free method is to overcome the assumption of model fitting method and to determine the conversion-dependent activation energy. Therefore, model free analysis is a complementary approach to evaluate the reaction kinetics and activation energy. Friedman method, one of model free methods, was applied in this study. It can be expressed by equation (5):17

E  dα  ln  =ln( Af ( a ) ) - α α RT  dt α

(5)

where Eα is the activation energy at different dehydration fraction. Eα was calculated from the slope of straight line of ln(dα/dt) α vs. -1000/RT and was shown in Table 2. In Table 2, for the 1st-step dehydration, Eα increased in the initial stage (0.1≤α≤0.2). Eα in the early stage is commonly affected by many factors14, 26, the increase in Eα in this case may be affected by steric hindrance. Then the Eα remained a constant level around 120.0 kJ·mol-1 when α ranged from 0.2 to 0.7, indicating a stable escaping process of water molecules through the channels. At the end stage, the Eα decreased to a relatively low value of 89.8 kJ·mol-1 when α=0.9. This decrease in Eα may be attributed to the increasing active defects formed during the dehydration reaction. While for the 2nd-step dehydration, the Eα remained almost a constant level around 85.0 kJ·mol-1 when the reaction proceeded. The constant dehydration activation energy indicates that there are no different resistances in controlling the remove rate of coordinated water molecules and a stable process of the remove of coordinated water molecules. Analysis by model free indicates that the average dehydration activation energies of the 1st-step dehydration and the 2nd-step dehydration are 113.0 kJ·mol-1 and 84.0 kJ·mol-1, respectively. This result is consistent with 114.9 kJ·mol-1 for R2 model in the 1st-step 12


Page 13 of 23

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


dehydration and 82.2 kJ·mol-1 for R3 model in the 2nd-step dehydration from model fitting analysis. The good consistence in dehydration activation energy obtained from model fitting analysis and model free analysis suggests that R2 model and R3 model are suitable for expressing the two-step dehydration of Hydrate I in isothermal mode.

3.3.3 Dehydration mechanism of Hydrate I. In this work, model fitting were performed for the data 0.2≤α≤0.827, R2 model and R3 model are found to be the most appropriate models for the 1st-step dehydration and the 2nd-step dehydration, respectively. They both belong to geometrical contraction models where the rate-limiting step is the inward advance of the phase boundary from the surface to the center of the crystals.13, 21, 28

A packing diagram of Hydrate I of SC was given in Figure 8 where channel for water to escape within the crystal is shown. Two-dimensional channels were formed by expanding the a-axis paralleled channels along the b-axis in unit cell. The water escapes along such two-dimensional channels belongs to the two-dimensional phase boundary reaction model (R2), which is consistent to the results of model fitting analysis. While in the 2nd-step dehydration, the channels no longer exist due to the collapse and reorganization of the structure. Water remaining is confined in the crystal. Thus the three-dimensional phase boundary reaction (R3) mechanism is reasonable for the 2nd-step dehydration.

CONCLUSIONS The structure of an unreported hydrate of SC (Hydrate I) was discovered. Hydrate I has a monoclinic symmetry and belongs to P21 space group. There are two types of water, 7 13



1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

channel-type water molecules (9.23 wt%) and 9 calcium-ion coordinated water molecules (11.87 wt%), in the unit cell of Hydrate I. A two-step dehydration process of Hydrate I was confirmed. For the 1st-step, the channel-type water dehydrated from 313.15 K to 363.15 K, resulting in the formation of Hydrate II. In the 2nd-step, the loss of the calcium-ion coordinated water began at 368.15 K and completed when temperature reached 453.15 K, leading to AP of SC. By model free analysis, the activation energy of the 1st-step dehydration varied with increasing dehydration fraction from 95.0 to 89.8 kJ·mol-1, while the activation energy of the 2nd-step dehydration kept almost constant. The apparent activation energy of the 1st-step dehydration (114.9 kJ·mol-1) is bigger than the 2nd-step dehydration (82.2 kJ·mol-1) according to model fitting analysis. This result may attributed to the energy necessary for cooperative release of channel-type water molecules and the cooperative reorganization is higher than destructive dehydration departure of coordinated water molecules. By model-fitting, R2 model was found to well describe the 1st-step dehydration of Hydrate I in isothermal mode, implying that channel-type water molecules release along channel directions with the two-dimensional movement of phase boundary, which is consistent with class II-Coop.-Reorg. dehydration. While R3 model is more suitable in the 2nd-step dehydration, suggesting that the dehydration process of calcium-ion coordinated water belongs to the 3D phase boundary reaction mechanism, which conforms to class I-Destr.-Disorg. dehydration. Two different mechanism for the two-step dehydration is related to the special crystal structure of Hydrate I of SC.

14


Page 14 of 23

Page 15 of 23

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


■ AUTHOR INFORMATION Corresponding Author *E-mail: [email protected]; Phone: 86-22-27405754; Fax: 86-22-27314971.

■ ACKNOWLEDGEMENTS This work was supported by the National Natural Science Foundation of China (No. 21176173) and the Tianjin Municipal Natural Science Foundation (No. 15JCZDC33200).

■ SUPPORTING INFORMATION X-ray crystallographic information file (CIF) is available for structure of hydrate of SC (Hydrate I). The hydrogen bonds for Hydrate I of SC are summarized in Table S1. Reaction models used in solid-state reaction kinetics are listed in Table S2. The results of fitting dehydration data with all models are listed in Table S3 and Table S4. Hot stage photomicrographs and infrared spectra of SC are shown in Figure S1 and Figure S2, respectively. ■ REFERENCES

(1) Braun, D. E.; Karamertzanis, P. G.; Arlin, J. B.; Florence, A. J.; Kahlenberg, V.; Tocher, D. A.; Griesser, U. J.; Price, S. L. Cryst. Growth Des. 2010, 11, 210. (2) Liu, Z.; Yin, Q.; Zhang, X.; Gong, J.; Xie, C. Ind. Eng. Chem. Res. 2014, 53, 3373. (3) Kim, Y. S.; Rousseau, R. W. Cryst. Growth Des. 2004, 4, 1211. (4) Singh, D.; Baruah, J. B. Cryst. Growth Des. 2011, 11, 768. 15



1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

(5) Koradia, V.; de Diego, H. L.; Elema, M. R.; Rantanen, J. J. Pharm. Sci. 2010, 99, 3966. (6) Brittain, H. G. Cryst. Growth Des. 2008, 8, 2588. (7) Morris, K. R.; Rodriguez-Hornedo, N. Encyclopedia of pharmaceutical technology; Marcel Dekker: New York, 1993. (8) Morris, K. R. Drugs and the pharmaceutical sciences; Marcel Dekker: New York, 1999. (9) Jørgensen, A. C.; Strachan, C. J.; Pöllänen, K. H.; Koradia, V.; Tian, F.; Rantanen, J. J. Pharm. Sci. 2009, 98, 3903. (10)Lester, C.; Lubey, G.; Dicks, M.; Andol, G.; Vaughn, D.; Cambron, R. T.; Poiesz, K.; Redman-Furey, N. J. Pharm. Sci. 2006, 95, 2631. (11) Bērziņš, A.; Actiņš, A. CrystEngComm 2014, 16, 3926. (12) Khankari, R. K.; Grant, D. J. W. Thermochim. Acta 1995, 248, 61. (13) Khawam, A.; Flanagan, D. R. J. Phy. Chem. B 2006, 110, 17315. (14) Sheth, A. R.; Zhou, D.; Muller, F. X.; Grant, D. J. J. Pharm. Sci. 2004, 93, 3013. (15) Pérez-Maqueda, L.; Criado, J.; Sánchez-Jiménez, P. J. Phy. Chem. A 2006, 110, 12456. (16) Vyazovkin, S.; Wight, C. A. Thermochim. Acta 1999, 340, 53. (17) Zhou, D.; Schmitt, E. A.; Zhang, G. G.; Law, D.; Wight, C. A.; Vyazovkin, S.; Grant, D. J. J. Pharm. Sci. 2003, 92, 1367. (18) Bērziņš, A.; Rekis, T.; Actiņš, A. Cryst. Growth Des. 2014, 14, 3639. (19) Pan, F.; Wang, R.; Englert, U. CrystEngComm 2013, 15, 1164. 16


Page 16 of 23

Page 17 of 23

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


(20) Ogruc-Ildiz, G.; Akyuz, S.; Ozel, A. E. J. Mol. Struct. 2009, 924, 514. (21) Khawam, A.; Flanagan, D. R. J. Pharm. Sci. 2006, 95, 472. (22) Petit, S.; Coquerel, G. Chem. Mater. 1996, 8, 2247. (23) Vyazovkin, S. Int. J. Chem. Kinet. 1996, 28, 95. (24) Laidler, K. J. J. Chem. Educ. 1984, 61, 494. (25) Vyazovkin, S.; Burnham, A. K.; Criado, J. M.; Pérez-Maqueda, L. A.; Popescu, C.; Sbirrazzuoli, N. Thermochim. Acta 2011, 520, 1. (26) Manche, E. P.; Carroll, B. Thermochim. Acta 1978, 24, 1. (27) Kons, A.; Rutkovska, L.; Bērziņš, A.; Bobrovs, A.; Actiņš, A. CrystEngComm 2015, 17, 3627. (28) Dong, Z.; Salsbury, J. S.; Zhou, D.; Munson, E. J.; Schroeder, S. A.; Prakash, I.; Vyazovkin, S.; Wight, C. A.; Grant, D. J. J. Pharm. Sci. 2002, 91, 1423.

17



1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Figures

Figure 1. Preparation reaction of SC.

Figure 2. Crystal structure of Hydrate I of SC (a, b). The red and white spheres represent water molecules in (a) and (b). In (b), hydrogen atoms and the coordinated water are omitted, Hydrate I of SC is viewed along the a-axis.

18


Page 18 of 23

Page 19 of 23

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


Figure 3. TGA (a, left axis) and DSC (b, right axis) curves of Hydrate I

Figure 4. SEM photographs of Hydrate I (a), Hydrate II (b), and AP (c).

19



1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Figure 5. Powder X-ray diffraction patterns of different solid states of SC (a) and PXRD patterns during the transformation process from Hydrate I to AP (b).

Figure 6. Isothermal dehydration kinetic curves of the 1st-step (a) and the 2nd-step (b) at different heating temperatures.

20


Page 20 of 23

Page 21 of 23

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


Figure 7. The two-step dehydration activation energy Eα vs. α for Hydrate I in isothermal mode.

Figure 8. A packing diagram of Hydrate I of SC. The hydrogen atoms and coordinated water are omitted, the red spheres represent oxygen atoms, the shaded waves show water channels in the crystal.

21



1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Tables

Table 1. Crystallographic data of Hydrate I Empirical formula

C40H68Ca2N16O24S4

Formula weight

1365.50

Crystal system

monoclinic

Space group

P21

a(Å)

13.850

b(Å)

15.604

c(Å)

14.083

α(°)

90

β(°)

90.44

γ(°)

90

Volume(Å3)

3043.5

Density(g/cm3)

1.491

Z

2

Rint

0.0535

goodness-of-fit

1.036

Final R indices[I>2sigma(I)]

R1=0.0498，wR2=0.1008

R indices(all data)

R1=0.0729，wR2=0.1104

22


Page 22 of 23

Page 23 of 23

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


Table 2. The 1st-step and the 2nd-step dehydration activation energies of Hydrate I in isothermal mode. Dehydration fraction

Dehydration activation energy Eα/( kJ·mol-1)

α

1st-step

R2

2nd-step

0.1

95.0±6.9

0.9784

92.4±8.4

0.9937

0.2

124.1±17.4

0.9984

84.5±16.4

0.9917

0.3

126.9±15.0

0.9866

82.9±12.3

0.9893

0.4

120.7±16.9

0.9826

82.9±6.1

0.9876

0.5

118.8±17.6

0.9851

83.9±7.3

0.9861

0.6

118.6±17.2

0.9819

83.6±4.1

0.9856

0.7

114.6±15.3

0.9839

80.4±6.0

0.9859

0.8

108.9±14.2

0.9910

81.7±5.5

0.9898

0.9

89.8±18.2

0.9749

83.9±1.5

0.9980

23


R2

Preparation and Dehydration Kinetics of Complex Sulfadiazine

Recommend Documents