Trehalose dihydrate

Avastin Avastin is used for the treatment of colorectal cancer. It is supplied in 100 and 400 mg dosages. The 100 mg formulation consists of 240 mg a,a-trehalose dihydrate, 23.2 mg sodium phosphate (monobasic, monohydrate), 4.8mg sodium phosphate (dibasic, anhydrous), 1.6mg polysorbate 20 and water-for-injection. 

D-Trehalose dihydrate (Sigma, St. Louis, MO, USA) store powder at ambient temperature. 

C Ascend-, (a-D-glucosido)-a-D-glucoside mycose natural trehalose a,a-trehalose trehalose dihydrate. 

It should be noted that although trehalose dihydrate is quoted to have a melting point of 97°C, the true nature of this melting process has been the subject of debate in the literature,including the transformation of the dihydrate into the anhydrous form. Anhydrous crystalline trehalose has been reported to melt at 203°C, although higher values (215°C) have also been quoted in the literature. 

Taylor LS, York P. Characterisation of the phase transitions of trehalose dihydrate on heating and subsequent dehydration. / Pharm Sci 1998 87 347-355. 

The in situ Raman spectroscopy method has also been used to study the particle size-dependent molecular rearrangements that take place during the dehydration of trehalose dihydrate.73 Different phases were sieved into fractions <45-pm and >425-pm particle size, and the Raman spectra obtained at various times during an isothermal heating at 80°C. After being heated for 210 minutes, the <45-pm dihydrate material appeared to become amorphous while the >425-pm dihydrate material transformed into the crystalline anhydrate phase. Ratios of various characteristic scattering peaks were used to follow the kinetics of the phase transformations. 

The authors gratefully acknowledge the financial support from a Grant-in-Aid for JSPS Fellows provided by The Ministry of Education, Culture, Sports, Science and Technology of Japan. The authors thank Prof. M. Tanaka and Dr. S. Ishizaki (Tokyo University of Marine Science and Technology) for the use of the UV-spectrometer, and Dr. H. Chaen (Hayashibara Biochemical Lab. Inc., Japan) for providing trehalose dihydrate reagent. 

GB (anhydrous, purity >98%), L-proline, glycine, glucose, and trehalose (dihydrate) were purchased from Wako Pure Chemical Industry, Ltd (Osaka, Japan), and used without further purification. 

Akao et al. investigated the dehydration of trehalose dihydrate to yield form II under supercritical fluid conditions (21). Trehalose form II is a metastable crystalline form of trehalose anhydrate and can be readily converted into the dihydrate by exposure to a moist environment at room temperature (22). Trehalose form III is another anhydrous polymorph. The phase transition behavior, detected by Fourier transform infrared (FTIR) spectroscopy and confirmed by first-derivative euclidean distance analysis (FDE), was found to be dependent on the extraction time, temperature, and pressure of SCCO2. At 20 MPa, an increase in temperature from 70°C to 90°C augmented the dehydration rate of trehalose dihydrate. Thus it appears that a temperature higher than 70 °C at 20 MPa is required for dehydration of trehalose dihydrate. The polymorphic forms obtained at different temperatures and pressures are summarized in Table 1. 

Table 1 Phase Transition of Trehalose Dihydrate Under Supercritical Fluid Conditions at Different Temperatures...

Akao K, Okubo Y, Inoue Y, Sakurai M. Supercritical CO2 fluid extraction of crystal water from trehalose dihydrate. Efficient production of form II T ) phase. Carbohydr Res 2002 337 1729-1735. 

Taga, T., Senma, M., OsaM, K. (1972). The crystal and molecular structure of trehalose dihydrate, Acta Cryst., B28 3258. 

Ci2H220u-2H20 a,a-Trehalose dihydrate a-n-glucopyranosyl a-n-glu-copyranoside dihydrate, m.p. 96-97°C... 

Katon et al. (1967 1969) used liquid-nitrogen temperature to investigate the detailed structure of crystalline sugars and the usefulness of infrared spectroscopy in the differentiation of sugars. Some of their spectra cover the range from 4000 to 33 cm" Figure 3.17 shows the infrared spectrum of a,a-trehalose dihydrate at both room temperature and 113°K recorded from a Nujol mull. (Similar results are... 

CAS 99-20-7 EINECS/ELINCS 202-739-6 Synonyms Ergot sugar o-D-Glucopyranoside, a-D-glucopyranosyl- a-D-Glucopyranosyl-a-D-glucopyranoside Mycose Natural trehalose a-Trehalose a,a-Trehalose D-(+)-Trehalose Trehalose, dihydrate Classification Disaccharide Empirical C12H22O11... 

H26O13, a,a-Trehalose dihydrate, 38B, 441 2H29BrCaOi6f Calcium lactobionate bromide hydrate, 39B, 311 2H3oCaCl20i 5, Bis-(/3-D-f ructopyranose) calcium chloride trihydrate, 40B, 657... 

In situ thermal transitions were also described by Taylor et al., who examined the isothermal dehydration behavior of trehalose dihydrate [29]. For small particle size fractions (<45 fjLm), heating at 80°C caused loss of peak definition until, at 210 min, amorphous material was present. In contrast, a larger particle size fraction (>425 fim) converted to the crystalline anhydrous form of the material. The kinetics of this conversion was probed from the Raman data using peak height ratios with time a two-stage rearrangement was indicated. A broader consideration of pharmaceutical hydrates, including their characterization by several techniques (NMR, Raman spectroscopy, and isothermal calorimetry) can be found in the literature [30] as can a review of the use of spectroscopic techniques for the characterization of polymorphs and hydrates [31]. 

LS Taylor, AC Williams, P York. Particle size dependent molecular rearrangements during the dehydration of trehalose dihydrate—in situ FT-Raman spectroscopy. Pharm Res 15 1207-1214, 1998. RK Khankari, DJW Grant. Pharmaceutical hydrates. Thermochim Acta 248 61-79, 1995. 

Materials Acety 1 cholinesterase from an electric eel, (EC 3.1.1.7,1 OOOU/mg), acetylthiocholine chloride, 5,5 -dithiobis (2-nitrobenzoic acid), D (+) trehalose dihydrate, D (+) glucose, pyridostigmine bromide, and neostigmine bromide were from Sigma Chemical/Aldrich. Aldicarb, carbaryl, carbofuran, chlorpyrifos, chlorpyrifos-oxon, dichlorvos, methomyl, malathion, malaoxon, naled, paraoxon, parathion, trichlorfon, azinphos-methyl, diclofenthion, dimethoate, dimethoate-oxon, terbufos, phosmet, and fenthion were obtained from Chem Service Corp. All others chemicals used were reagent grade. Deionized water (DI) was used for the preparation of all solutions. 

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