Determination of the crystallinity of cephalexin in pharmaceutical formulations by chemometrical near-infrared spectroscopy

Background: Near-infrared (NIR) spectroscopy has gained wide acceptance in the pharmaceutical industry as a rapid and non destructive method for drug identification and the determination of the drug content of preparations. Aim: The crystallinity of cephalexin (CEX) in microcrystalline cellulose (MCC) was determined using a nondestructive NIR reflectance spectroscopic technique. The molecular interaction of a ground amorphous solid of CEX was investigated by the method. Method: Six kinds of standard material with various degrees of crystallinity were prepared by the physical mixing of crystalline, amorphous CEX, and MCC. X-ray powder diffraction profiles and NIR spectra were recorded for standard samples. A chemometric analysis of the NIR spectral data sets was conducted using principal component regression (PCR). Results: The correlation between the actual crystallinity of CEX and that predicted using the conventional X-ray diffraction method showed a straight line with a slope of 1.000, an intercept of ?2.071 × 10^?5 and a correlation coefficient of determination (R²) of 0.974. The NIR spectrum of amorphous CEX showed significantly different peaks at 1176 and 1206 nm because of the CH₃ group from those of CEX. PCR was performed on various kinds of pretransformed NIR spectral data sets of standard samples of CEX. To minimize the SE of cross-validation (SECV), the spectral data sets were subjected to the leave-one-out method. The second derivative treatment in the range of 1176–1206 nm yielded the lowest SECV values. Based on a two-component model, a plot of the calibration data between the actual crystallinity of CEX and that predicted by the NIR method was obtained. The plot showed a straight line (Y = 0.995X + 0.117 and R² = 0.994; n = 18). The mean bias for the NIR and X-ray powder diffraction methods was calculated to be 1.52% and 2.26%, and mean accuracy was 3.06% and 7.14%, respectively. Conclusion: NIR spectral changes of crystalline CEX during grinding suggested that the intermolecular hydrogen bonds between the amino and carboxyl groups are destroyed and the binding of methyl groups is heightened by the resonance effect of carboxyl groups, and the crystals are transformed into amorphous CEX.     

19F solid-state NMR spectroscopic investigation of crystalline and amorphous forms of a selective muscarinic M3 receptor antagonist,in both bulk and pharmaceutical dosage form samples

The purpose of the following investigation was to display the utility of ¹⁹F solid-state nuclear magnetic resonance (NMR) in both distinguishing between solid forms of a selective muscarinic M₃ receptor antagonist and characterizing the active pharmaceutical ingredient in low-dose tablets. Ambient- and elevated-temperature solid-state ¹⁹F fast (15 kHz) magic-angle spinning (MAS) NMR experiments were employed to obtain desired spectral resolution in this system. Ambient sample temperature combined with rotor frequencies of 15 kHz provided adequate ¹⁹F peak resolution to successfully distinguish crystalline and amorphous forms in this system. Additionally, elevated-temperature ¹⁹F MAS NMR further characterized solid forms through ¹⁹F resonance narrowing brought about by the phenomenon of solvent escape. Similar solvent dynamics at elevated temperatures were utilized in combination with ambient-temperature ¹⁹F MAS NMR analysis to provide excipient-free spectra to unambiguously identify the active pharmaceutical ingredient (API) conversion from crystalline Form I to the amorphous form in low-dose tablets. It is shown that ¹⁹F solid-state NMR is exceptionally powerful in distinguishing amorphous and crystalline forms in both bulk and formulation samples.     

Infrared-to-visible conversion luminescence of Er ions in lead borate transparent glass-ceramics

Transparent glass-ceramics were successfully prepared during controlled heat treatment of lead borate glasses. The PbF₂ particles were dispersed into a borate glass matrix which was evidenced by X-ray diffraction analysis. The phase identification revealed that crystalline peaks can be related to the orthorhombic PbF₂ phase. Green up-conversion luminescence due to the ⁴S_3/2–⁴I_15/2 transition of Er³⁺ ions was registered. In comparison to the precursor glass the luminescence intensity was considerably higher, whereas the luminescence linewidth slightly decreased in the studied oxyfluoride transparent glass-ceramics. It indicated that a part of the trivalent erbium was incorporated into the PbF₂ crystalline phase.     

Investigating the effect of moisture protection on solid-state stability and dissolution of fenofibrate and ketoconazole solid dispersions using PXRD,HSDSC and Raman microscopy

Enhanced dissolution of poorly soluble active pharmaceutical ingredients (APIs) in amorphous solid dispersions often diminishes during storage due to moisture-induced re-crystallization. This study aims to investigate the influence of moisture protection on solid-state stability and dissolution profiles of melt-extruded fenofibrate (FF) and ketoconazole (KC) solid dispersions. Samples were kept in open, closed and Activ-vials^® to control the moisture uptake under accelerated conditions. During 13-week storage, changes in API crystallinity were quantified using powder X-ray diffraction (PXRD) (Rietveld analysis) and high sensitivity differential scanning calorimetry (HSDSC) and compared with any change in dissolution profiles. Trace crystallinity was observed by Raman microscopy, which otherwise was undetected by PXRD and HSDSC. Results showed that while moisture protection was ineffective in preventing the re-crystallization of amorphous FF, KC remained X-ray amorphous despite 5% moisture uptake. Regardless of the degree of crystallinity increase in FF, the enhanced dissolution properties were similarly diminished. Moisture uptake above 10% in KC samples also led to re-crystallization and significant decrease in dissolution rates. In conclusion, eliminating moisture sorption may not be sufficient in ensuring the stability of solid dispersions. Analytical quantification of API crystallinity is crucial in detecting subtle increase in crystallinity that can diminish the enhanced dissolution properties of solid dispersions.     

Characterization of plasma-sprayed hydroxyapatite by31P-MAS-NMR and the effect of subsequent annealing

The characterization of plasma spray induced changes become complicated by the formation of amorphous phases.³¹P magic angle spinning (MAS)-nuclear magnetic resonance (NMR) measurements are suited to detect both crystalline and amorphous calcium phosphates. Therefore, we used³¹P-MAS-NMR and X-ray diffraction (XRD) to characterize plasma-sprayed hydroxyapatite. Besides small quantities of nearly unchanged crystalline apatite, disordered partly X-ray amorphous apatite was detected. Additionally, a non-stoichiometric amorphous calcium phosphate phase possessing a structure similar to TCP, probably calcium enriched, was observed. No indications of tetracalciumphosphate could be found. The decomposition of apatite during plasma spraying is reversible. An additional annealing procedure of plasma-sprayed hydroxyapatite at suitable temperatures above 500 °C rebuilds crystalline apatite structure.     

Quantifying low amorphous or crystalline amounts of alpha-lactose-monohydrate using X-ray powder diffraction, near-infrared spectroscopy, and differential scanning calorimetry

Efficient and accurate quantification of low amorphous and crystalline contents within pharmaceutical materials still remains a challenging task in the pharmaceutical industry. Since X-ray powder diffraction (XRPD) equipment has improved in recent years, our aim was 1) to investigate the possibility of substantially lowering the detection limits of amorphous or crystalline material to about 1% or 0.5% w/w respectively by applying conventional Bragg Brentano optics, combined with a fast and simple evaluation technique; 2) to perform these measurements within a short time to make it suitable for routine analysis; and 3) to subject the same data sets to a partial least squares regression (PLSR) in order to investigate whether it is possible to improve accuracy and precision compared to the standard integration method. Near-infrared spectroscopy (NIRS) and differential scanning calorimetry (DSC) were chosen as reference method. As model substance, alpha lactose monohydrate was chosen to create calibration curves based on predetermined mixtures of highly crystalline and amorphous substance. In contrast to DSC, XRPD and NIRS revealed an excellent linearity, precision, and accuracy with the percent of crystalline amount and a detectability down to about 0.5% w/w. Chemometric evaluation (partial least squares regression) applied to the XRPD data further improved the quality of our calibration.     

Sputter deposition of semicrystalline tin dioxide films

Tin dioxide is emerging as an important material for use in copper indium gallium diselenide based solar cells. Amorphous tin dioxide may be used as a glass overlayer for covering the entire device and protecting it against water permeation. Tin dioxide is also a viable semiconductor candidate to replace the wide band gap zinc oxide window layer to improve the long-term device reliability. The film properties required by these two applications are different. Amorphous films have superior water permeation resistance while polycrystalline films generally have better charge carrier transport properties. Thus, it is important to understand how to tune the structure of tin dioxide films between amorphous and polycrystalline. Using X-ray diffraction (XRD) and Hall-effect measurements, we have studied the structure and electrical properties of tin dioxide films deposited by magnetron sputtering as a function of deposition temperature, sputtering power, feed gas composition and film thickness. Films deposited at room temperature are semicrystalline with nanometer size SnO₂ crystals embedded in an amorphous matrix. Film crystallinity increases with deposition temperature. When the films are crystalline, the X-ray diffraction intensity pattern is different than that of the powder diffraction pattern indicating that the films are textured with (101) and (211) directions oriented parallel to the surface normal. This texturing is observed on a variety of substrates including soda-lime glass (SLG), Mo-coated soda-lime glass and (100) silicon. Addition of oxygen to the sputtering gas, argon, increases the crystallinity and changes the orientation of the tin dioxide grains: (110) XRD intensity increases relative to the (101) and (211) diffraction peaks and this effect is observed both on Mo-coated SLG and (100) silicon wafers. Films with resistivities ranging between 8 mΩ cm and 800 mΩ cm could be deposited. The films are n-type with carrier concentrations in the 3 × 10¹⁸ cm^− 3 to 3 × 10²⁰ cm^− 3 range. Carrier concentration decreases when the oxygen concentration in the feed gas is above 5%. Electron mobilities range from 1 to 7 cm²/V s and increase with increasing film thickness, oxygen addition to the feed gas and film crystallinity. Electron mobilities in the 1-3 cm²/V s range can be obtained even in semicrystalline films. Initial deposition rates range from 4 nm/min at low sputtering power to 11 nm/min at higher powers. However, deposition rate decreases with deposition time by as much as 30%.     

Solid-state gallium NMR characterization of cubic gallium nitride prepared by the reaction of gallium arsenide with ammonia

The reaction of cubic gallium arsenide (GaAs) with ammonia yielded gallium nitride (GaN). Powder X-ray diffraction patterns of the GaN products showed that they are a mixture of c- and w-GaN, while their Ga MAS NMR spectra revealed that they have the other phase of GaN besides c- and w-GaN and the high reaction temperature (≥900 °C) induces nitrogen deficiency in GaN. The peaks at 353 and 347 ppm in the ⁷¹Ga MAS NMR spectra were tentatively assigned to c-GaN and an intermediate of w- and c-GaN in the stacking order, respectively. The observed ⁷¹Ga chemical shifts of GaN, GaP, GaAs and GaSb in cubic phase were well correlated with the reciprocal of their band gaps.     

Crystallinity and luminescent properties of citrate sol-gel derived BAM phosphor

By adopting a facile citrate sol-gel process, pure well-crystallized BaMgAl₁₀O₁₇:Eu²⁺(BAM) blue phosphors were successfully prepared. The crystallinity, particle size, morphology, chemical composition and luminescent properties were characterized by XRD, FE-SEM, EDS and spectrofluorometer respectively. The results indicated the precursor was amorphous below 800 °C, and begun to crystallize at 1100 °C. The synthesis temperature decreased by about 300 °C compared to solid-state method to prepare BAM. FE-SEM images showed a well-crystallized, platelet morphology with a particle size of 1-3 μm. The obtained BAM phosphors were fine powders and had higher luminescent intensity compared to solid-state derived BAM phosphors due to high purity and perfect crystalline morphology.     

Structural characterization of boron doped hydrogenated nanocrystalline silicon films

Structural properties of boron doped hydrogenated nanocrystalline silicon films deposited by plasma enhanced chemical vapor deposition method were mainly characterized with Raman and X-ray diffraction methods. The experimental Raman data were fitted better by Fano effect profiles than those by phonon confinement effect line shapes chiefly due to high efficiency doping in grown films. The measured Raman spectra were deconvoluted into three-Gaussian profile components: around the peak positions 520 and 480 cm⁻¹ which contribute from crystalline and amorphous tissues separately, as well as a curve centered at about 500 cm⁻¹, which is attributed to the presence of grain boundaries. The average crystalline grain size and crystalline volume fraction were valued with Raman and X-ray diffraction techniques, respectively, while the error derived from different methods was elucidated. Accordingly, the structural changes including crystallites, grain boundaries and amorphous matrices in doped films with boron doping level were analyzed.     

The importance of the network-modifying element content in fly ash as a simple measure to predict its strength potential for alkali-activation

Six different Class F fly ashes were examined to identify the material properties that determine the strength development in geopolymerization. All of the fly ashes displayed typical features of Class F fly ash in chemical and mineral composition, amorphous phase (glass) content, and X-ray diffraction pattern profile; however, the strength developments of the ashes were quite different from each other. The results suggest that the strength is higher under the following configuration: greater content of network modifying elements, greater glass content, lower silicon content, lower intensity of quartz-related ²⁹Si NMR peak, and higher fraction of Al(IV) in the ²⁷Al NMR spectrum. Among the possibilities, the network-modifying elemental content may be the simplest and most accurate measure for strength development of alkali activation of fly ash.     

A new yellowish green luminescent material SrMoO4:Tb

A novel yellowish green phosphor tervalent terbium (Tb³⁺) doped strontium molybdate (SrMoO₄) was synthesized by conventional solid-state reaction method and its crystal structure and luminescent properties are investigated in this paper. The X-ray diffraction patterns (XRD) showed that the phosphor sintered at 750 °C for 3 h was a pure SrMoO₄ phase. The excitation spectrum consisted of two bands and the two excitation peaks located at 375 nm and 488 nm respectively. The emission spectrum was composed of four narrow bands, in which the strongest emission was located at 548 nm. The particle size analysis indicated that the median particle size D₅₀ = 2.89 μm and range of particle size distribution was narrow. These results showed that the SrMoO₄:Tb³⁺ phosphor was a promising yellowish green phosphor for ultraviolet light emitting diode (UVLED) and blue LED based white LED. The appropriate concentration of Tb³⁺ was 5 mol% for the highest emission intensity at 548 nm. Natrium ion (Na⁺) was found to be a promising charge compensator for SrMoO₄:Tb³⁺ phosphor.     

Magnesium analogues of aluminosilicate inorganic polymers (geopolymers) from magnesium minerals

Attempts to synthesise magnesium-containing analogues of aluminosilicate geopolymers from the 1:1 and 2:1 layer magnesiosilicate minerals chrysotile and talc, as well as the magnesium mineral sepiolite are reported. The effect of pre-treating these starting minerals by grinding and/or dehydroxylation was also investigated by XRD, ²⁹Si and natural-abundance ²⁵Mg solid-state magic angle spinning (MAS) NMR spectroscopy. The products from sepiolite most closely resembled an aluminosilicate geopolymer, setting at 40 °C to an X-ray amorphous product containing a broad characteristic ²⁹Si MAS NMR resonance at ?90 ppm. The ²⁵Mg MAS NMR spectrum of this product also showed evidence that some of the Mg was located in tetrahedral sites, as expected for a conventional geopolymer. A similar ²⁵Mg MAS NMR result was obtained for chrysotile, but talc proved to be extremely resistant to geopolymer synthesis, requiring treatment at 120 °C for 3 days to set to a friable material retaining the XRD and NMR characteristics of the original talc or its crystalline dehydroxylation products. This lack of reactivity may be related to the 2:1 layer-lattice talc structure, or to the fact that a suitably reactive amorphous product is not formed upon dehydroxylation.     

Luminescence of Cr-doped ZnGa2O4 thin films deposited by pulsed laser ablation

Chromium-doped zinc gallate powder is synthesized via a solid-state reaction and subsequently deposited as a thin film on quartz substrates by using a pulsed laser deposition technique under two different deposition conditions. The films are characterized with X-ray diffraction, scanning electron microscopy, UV-vis spectrophotometry and luminescent measurements. As the oxygen pressure is changed from 0 to 1 Pa, we find that the grain size gets smaller, the crystallinity improves, the band-gap energy increases, the excitation peaks of the charge transfer band exhibit a remarkable blue-shift from 263 to 247 nm and the intensity of the red emission (694 nm) is enhanced. The results suggest that the structural and luminescent properties of ZnGa₂O₄:Cr^3 + thin film phosphors are improved by deposition at an oxygen pressure of 1 Pa.     

Structure characterization of heat set and drawn polyamide 66 fibers by FTIR spectroscopy

Structural changes that occur during thermally induced and strain induced crystallization of polyamide 66 fibers were studied by infrared spectroscopy, density measurement and optical microscopy. Two bands at 924 and 1136 cm^–1 were shown to arise from the amorphous phase and assignment of the bands at 936 and 1200 cm^–1 to the crystalline phase were confirmed. We demonstrated that two different infrared spectroscopic methods could be used to determine the total crystallinity of polyamide 66 fibers. One is a calibration method in which the band ratio of 1200 and 1630 cm^–1 is plotted against the crystallinity measured by density measurements. The other one is an independent infrared method. Crystallinity obtained by the independent infrared spectroscopic method showed good agreement with crystallinity observed by density measurement. Infrared dichroism was used to obtain the crystalline orientation using the band at 936 cm^–1. The transition moment angle of 48° was found for the band at 936 cm^–1 with respect to chain axis. Amorphous orientation was obtained using Stein’s equation. Received: 18 September 2000 / Reviewed and accepted: 20 September 2000     

Properties of Iron Oxide Nanoparticles Synthesized at?Different?Temperatures

Iron oxide nanoparticles were synthesized by co-precipitation in air atmosphere at different temperatures and their structural and magnetic properties were investigated. The mean particle sizes of iron oxide nanoparticles were calculated from the X-ray diffraction (XRD) patterns using the Scherrer equation. Fourier transform infrared spectroscopy analysis exhibited the vibration bands at 563 cm^?1 and 620 cm^?1 confirming the formation of Fe₃O₄ and ??-Fe₂O₃, respectively. Morphological observation was made by a transmission electron microscope and the particle size of iron oxide nanoparticles was found to be around 9 nm which is consistent with the particle size calculated according to the XRD patterns. It was observed that the intensity of the peaks in the patterns and crystallinity increased as the temperature increased. Magnetization curves showed zero coercivities indicating that the samples are superparamagnetic.     

Preparation of (ZnO)1−x(GaN)x:Mn powder and its photoluminescence properties

(ZnO)_1−x(GaN)_x:Mn²⁺ powder was prepared by a conventional solid-state reaction under an NH₃ gas flow. The sample preparation conditions including the mixing ratio of the raw materials, the annealing temperature, and the annealing time were varied. The crystallinity and the photoluminescence (PL) intensity of this fluorescent material were improved by increasing the amount of ZnO and by increasing the annealing time, and no changes was observed in the PL wavelength. The crystallinity of the samples was enhanced and the PL intensity increased markedly at annealing temperatures of 700 °C and 800 °C, respectively. Moreover, it was clarified that the sample could be synthesized at annealing temperatures of above about 650 °C.     

~1H固体核磁共振技术对管材用Cr系催化剂催化乙烯共聚物及不同耐压等级管材料的研究

以基于Cr系催化剂、不同己烯含量的管材用乙烯己烯共聚物为研究对象,应用1H固体NMR技术测定了其室温下的相结构参数以及不同温度下的相结构变化.研究发现,随着共聚单体含量的增加,NMR结晶相组分的含量降低,界面区和无定形区组分含量增加,且两者在NMR测定的长周期中所占的比例也增加.提出了以界面区含量和无定形区含量的比例随温度的变化作为定性判断非晶区中链段运动受限程度的依据.此外,采用相同的1H固体NMR技术研究了不同耐压等级聚乙烯管材料基体树脂的聚集态结构.发现室温下随着管材料耐压等级的增加,结晶相组分含量减少而其他两组分含量增加,且NMR测定的长周期中结晶相组分所占比例降低而其他两组分比例升高.实验结果证明,上述定性判断非晶区中链段运动受限程度的判据与材料的耐压等级有较好的对应关系.     

A novel green luminescent material AlPO4:Tb

A novel green phosphor Tb³⁺ doped AlPO₄ was synthesized by conventional solid-state reaction method. The phosphor showed prominent luminescence in green due to the ⁵D₄-⁷F₅ transition of Tb³⁺. Structural characterization of the luminescent material was carried out with X-ray powder diffraction (XRD) analysis. The XRD measurements indicated that there are no crystalline phases other than AlPO₄. Luminescence properties were analyzed by measuring the excitation and photoluminescence spectra. Photoluminescence measurements indicated that the phosphor exhibited bright green emission at about 542 nm under UV excitation. It is shown that the 3 mol% of doping concentration of Tb³⁺ ions in AlPO₄:Tb³⁺ phosphor is optimum. The measured chromaticity for the phosphors AlPO₄:Tb³⁺ under UV excitation is (0.32, 0.53).     

Effect of molecular weight on conformational changes of PEO: an infrared spectroscopic analysis

Effect of molecular weight on conformation, helix structure (H structure) and trans planar structure (T structure), of Poly(ethylene oxide) (PEO) has been investigated in detail by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and differential scanning calorimeter. Two main diffraction peaks at about 2θ = 19° and 23° are discovered, and XRD patterns reveal that the unit cell of crystalline PEO belongs to the monoclinic lattice. The crystallinity decreases from 93.82 to 59.62 %, and the deviation of crystalline temperature of PEO-0.5 is larger than those of the other three under four reheated cycles. From FTIR results, a red shift about 11 cm^?1 is observed in the stretching vibration of –C–O–C– with increasing molecular weight, suggesting the presence of chain–chain interactions to restrict the stretching vibration of -C–O–C– in main chains. Meanwhile, the bending region of –C–C–O– at about 533 cm^?1 sensitive to tension shifts to lower wavenumber, and a new peak at about 510 cm^?1 emerges with increasing molecular weight, which is the indicator of internal tension/strain and orientation. Furthermore, the peak intensity ratios of H structure decrease with increasing molecular weight. In contrast, T structure increases dramatically. Consequently, with respect to molecular weight, the possible interactions, entanglements and tie molecules, of PEO molecular chains to explain the difference between H and T structure is proposed, which is in agreement with the experimental observations quite well.