X-Ray Diffraction and Electron Microscopy in the Polymorphism Study of Ondansetron Hydrochloride

Using different techniques, we studied the possible formation of ondansetron polymorphs. Ondansetron is a carbazol antiemetic that acts as a competitive, selective inhibitor of 5-HT₃ serotonin receptors. The polymorphs were determined by X-ray diffraction (XRD) and scanning electron microscopy (SEM). The results suggest that the compounds are not true crystallographic polymorphs, but instead are the product of physical structural changes in the drug, which would be of interest pharmaceutically.     

Interconversion Studies of Betamethasone Acetate Polymorphs

ABSTRACT

The polymorph interconversions of Betamethasone Acetate (BA) were studied under various pharmaceutical conditions, such as grinding, heating and suspending in water, based on differential scanning calorimetry, thermogravimetric analysis, and X-ray powder diffraction. There existed enantiotropic relationships between the three polymorphs of BA, which were named form II, Iα, and Iβ work, respectively. It was concluded that form II was the most stable form when suspended in water.     

Solid dispersion particles of tolbutamide prepared with fine silica particles by the spray-drying method

Solid dispersion particles of tolbutamide (TBM) were prepared by formulating nonporous (Aerosil 200 (hydrophilic), Aerosil R972 (hydrophobic)) or porous (Sylysia 350 (hydrophilic), Sylophobic 200 (hydrophobic)) silica as a carrier and applying the spray-drying (SD) or evaporation (Eva) method. In the solid dispersion particles prepared by the SD method, TBM existed in a meta-stable form (Form II) irrespective of the type of silica. On the other hand, when the Eva method was used, various crystalline forms of TBM were observed in the solid dispersion particles according to the type of silica. Polymorphs of Forms III and IV were prepared with Aerosil 200 and Aerosil R972, respectively, while crystalline Form II was obtained when either of the forms of porous silica, Sylysia 350 or Sylophobic 200, was formulated. The dissolution property of TBM in the solid dispersion particles prepared with hydrophilic silica was remarkably improved compared with those of the original TBM crystals (Form I) or spray-dried TBM without silica (Form II). In the case of hydrophobic silica, the release rate of TBM from the solid dispersion particles was much slower than that of original TBM. The meta-stable form of TBM in the solid dispersion particles was stable for at least 4 weeks when stored at 60 °C and 0% RH, while the spray-dried TBM without silica (Form II) was gradually converted to the stable form (Form I) under the same storage conditions. Under the humid storage conditions (60 °C, 75% RH), the spray-dried TBM without silica (Form II) immediately converted into the stable form (Form I) within 1 day, while TBM (Form II) in the solid dispersions in a matrix of silica was stable for at least 1 week.     

Structural analysis of cellulose triacetate polymorphs by two-dimensional solid-state C-C and H-C correlation NMR spectroscopies

For the elucidation of the crystal structures of the two crystalline allomorphs of cellulose triacetate (CTA), namely CTA I and CTA II, two-dimensional (2D) solid-state through-bond ¹³C-¹³C and ¹H-¹³C correlations NMR techniques applied to the two crystalline allomorphs of CTA. As a result, the ¹³C and ¹H chemical shifts of the glucopyranose ring of CTA I and CTA II were completely assigned by the 2D NMR spectra of these allomorphs. On the 2D ¹³C-¹³C correlation spectrum of CTA II, two sets of the ¹³C-¹³C correlations from C1 to C6 were observed. This indicated that the CP/MAS ¹³C NMR spectrum of CTA II can be characterized by its overlapping of the ¹³C subspectra of two kinds of 2,3,6-triacetyl-anhydroglucopyranose units and that there are two magnetically non-equivalent sites in the unit cell of CTA II. In the case of CTA I, the numbers of respective ¹³C and ¹H shifts of CTA I agreed with the those of the glucopyranose residue in the allomorph, strongly suggesting that the asymmetric unit of CTA I is only one glucose residue. In addition, conformational differences in the exocyclic C5-C6 bonds between CTA I and CTA II were strongly suggested by the notable differences in the ¹H and ¹³C chemical shifts at the C6 sites of these allomorphs.     

Fourier Transform Raman Spectroscopy of the Four Crystallographic Phases of α, β, γ and ε 2,4,6,8,10,12‐Hexanitro‐2,4,6,8,10,12‐hexaazatetracyclo[5.5.0.05,9.03,11]dodecane (HNIW,CL‐20)

Fourier transform Raman Spectroscopy (Nd : YAG laser at 1064 nm) was used to characterize the four stable phases of 2,4,6,8,10,12‐Hexanitro‐2,4,6,8,10,12‐hexaazatetracyclo[5.5.0.0^5,9.0^3,11]dodecane (HNIW, CL‐20). Raman spectra are reported over the region from 0–4000 cm⁻¹_, relative to the laser line. A tentative assignment of the most predominant Raman peaks was made with the aid of QM calculations at the B3LYP/6‐31G(d) level. A method for detecting polymorphic impurities in ε‐CL‐20 was also developed. The detection level for polymorphic impurities was determined to be below 2%. A method for producing γ‐CL‐20 is also presented.     

Characterization of zopiclone crystal forms found among generic raw materials

This paper deals with the occurrence of polymorphs and pseudopolymorphs and their effect on the solid-state properties of zopiclone, a poorly water soluble nondiazepine sedative and hypnotic drug. X-ray powder diffraction (XRPD), infrared spectroscopy (IR), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), particle size analysis, dissolution studies, and solubility determinations were used to characterize the zopiclone raw materials. An anhydrated form, a dihydrated form, and a mixture of these two crystal forms were found and characterized among the zopiclone powders.     

磁黄铁矿结构性质与可浮性差异研究

磁黄铁矿主要有3个同质多象变体：六方磁黄铁矿、单斜磁黄铁矿和斜方磁黄铁矿。磁黄铁矿的化学组成、物理性质和晶体结构决定其可浮性、表面易氧化程度、性脆等特性。采用X射线衍射、电子探针和浮选试验,考察了单斜磁黄铁矿和六方磁黄铁矿的结构和成分及可浮性差异。结果表明,单斜比六方磁黄铁矿富含硫;单斜和六方磁黄铁矿浮选回收率随矿浆pH变化的规律类似,但是单斜磁黄铁矿的回收率比六方磁黄铁矿高,可浮性比六方磁黄铁矿好;酸性条件下,六方比单斜磁黄铁矿更容易被Cu²⁺活化;石灰对单斜磁黄铁矿的抑制作用不明显,而对六方磁黄铁矿具有一定的抑制作用。     

High-resolution electron microscopy of high-temperature superconductors

We review recent results obtained at Northwestern using high-resolution electron microscopy to study high-temperature superconductors. While in general these materials form large, very perfect single crystal grains which display very few imperfections, there is also evidence of slip defects, amorphous regions, and order-disorder transformations. We also report that the gadolinium-based superconductors and in one case yttrium-based superconductors show evidence for some copper solid solubility in the form of copperrich planar defects. The structure of a metastable trigonal polytype is also reported, as are the effects of electron beam and water vapor damage to the materials.     

Comparison of the Physical and Chemical Stability of Niclosamide Crystal Forms in Aqueous Versus Nonaqueous Suspensions

In an effort to produce physically stable and pharmaceutically acceptable suspensions of niclosamide, this study reports the differences in physical and chemical stability of aqueous vs. nonaqueous suspensions of a niclosamide anhydrate, two monohydrates H_A and H_B, a 1:1 niclosamide N,N‐dimethylformamide solvate, a 1:1 niclosamide dimethyl sulfoxide solvate, a 1:1 niclosamide methanol solvate, and a 2:1 niclosamide tetraethylene glycol hemisolvate. Evaluation of aqueous and nonaqueous suspensions showed that in aqueous suspensions anhydrous, and solvated niclosamide crystal forms were transformed to a monohydrate, H_A, which was reasonably stable but which did eventually transform to the most stable monohydrate H_B. The order in which these crystal forms transformed to monohydrate H_B were: Anhydrate?>?N,N‐dimethylformamide?>?dimethyl sulfoxide?>?methanol?>?tetraethylene glycol?>?monohydrate H_A. In a nonaqueous propylene glycol vehicle, the transformation to the monohydrous forms was not observed and on desolvation the solvated crystals transformed to the anhydrous form. In all cases, immediately upon desolvation or dehydration, the crystal structures of the desolvated materials were similar to that of the solvated materials. However, the isomorphic structures, formed after desolvation, were unstable and rehydrated or resolvated when exposed to the solvent or converted to the anhydrous form in a dry environment. The crystal forms remained chemically stable in both aqueous and nonaqueous suspensions for the length of the study.