XRPD analysis

Chitin metal silicates coprecipitates [53] Coprecipitation of a metal silicate on chitin particles offers industrial potential for use as a single filler which has binding as well as super-disintegration properties and can be used in directly compressed tablets or in wet granulation methodologies. The coprecipitation process causes physical adsorption of the metal silicates onto chitin particles (Fig. 2.39) without any chemical interaction which has been proved by IR and XRPD analysis. 

Diffuse reflectance IR spectroscopy has been used, in conjunction with XRPD analysis, to determine the levels of ranitidine Form-II in samples of... 

Although XRPD analysis is a relatively straightforward technique for the identification of solid-phase structures, there are sources of error, including the following ... 

The results obtained from the investigation of the crystallochemical properties of a family of mixed Li-vanadates of general formula LiCoyNi(i.y)V04 are reported. This kind of material is believed to be a valid alternative to the traditional positive electrode materials in the Li-ion cell, an electrochemical power source of outstanding importance in the portable electronics field. The powders, prepared via two different methods (a wet chemistry route and a solid state method), have been characterised by XRPD analysis, NMR and diffuse reflectance Vis-NIR spectroscopy. The findings allowed to correlate the electrochemical performance of the vanadates, which is higher for the samples prepared via wet chemistry, to the crystallinity of the powders and to the transition metal cations distribution. 

FIGURE 51.8. Combined CP-MAS interatomic distance measurements and XRPD analysis of cimetidine 2 form A. (a) Measurements of multiple through-space distances using CP-... 

The analysis of XRPD patterns is an important tool studying the crystallographic structure and composition of powder compounds including the possibility to study deviation from ideal crystallinity, i.e. defects. Looking at an X-ray powder diffractogram the peak position reflects the crystallographic symmetry (unit cell size and shape) while the peak intensity is related to the unit cell composition (atomic positions). The shape of diffraction lines is related to defects , i.e. deviation from the ideal crystallinity finite crystallite size and strain lead to broadening of the XRPD lines so that the analysis of diffraction line shape may supply information about sample microstructure and defects distribution at the atomic level. 

A derived crystal packing model proved to be useful in resolving the crystal structure of a metastable polymorph of racemic modafinil, where details of the solved crystal structure of one polymorph was used as a basis for developing the structure of the other [12]. It was found that the calculated XRPD pattern matched well with the experimental data, indicating the correctness of the analysis. The powder diffraction of two polymorphs of chlorothalonil were solved to obtain... 

Although simple intensity correction techniques can be used to develop very adequate XRPD methods of quantitative analysis, the introduction of more sophisticated data acquisition and handling techniques can greatly improve the quality of the developed method. For instance, improvement of the powder pattern quality through the use of the Rietveld method has been used to evaluate mixtures of two anhydrous polymorphs of carbamazepine and the dihydrate solvatomorph [43]. The method of whole pattern analysis developed by Rietveld [44] has found widespread use in crystal structure refinement and in the quantitative analysis of complex mixtures. Using this approach, the detection of analyte species was possible even when their concentration was less than 1% in the sample matrix. It was reported that good quantitation of analytes could be obtained in complex mixtures even without the requirement of calibration curves. 

XRPD method that is suitable for analysis of real samples. 

Another example of a well-designed method for the quantitative XRPD determination of polymorphs was developed for the phase analysis of prazosin hydrochloride [49]. As an example of an XRPD method for the determination of solvatomorphs, during the quantitation of cefepine dihydrochloride dihydrate in bulk samples of cefepine dihydrochloride monohydrate, a limit of detection of 0.75% w/w and a limit of quantitation of 2.5% w/w were associated with a working range of 2.5-15% w/w [50],... 

An XRPD system equipped with a heatable sample holder has been described, which permitted highly defined heating up to 250°C [55]. The system was used to study the phase transformation of phenan-threne, and the dehydration of caffeine hydrate. An analysis scheme was developed for the data that permitted one to extract activation parameters for these solid-state reactions from a single non-isothermal study run at a constant heating rate. 

For example, amorphous clarithromycin was prepared by grind and spray-drying processes, and XRPD was used to follow changes in crystallinity upon exposure to elevated temperature and relative humidity [59]. Exposure of either substance to a 40°C/82% RH environment for seven days led to the formation of the crystalline form, but the spray-dried material yielded more crystalline product than did the ground material. This finding, when supported with thermal analysis studies, led to the conclusion that the amorphous substances produced by the different processing methods were not equivalent. 

The solid-state properties like crystallinity, polymorphism (crystal structure), shape (morphology), and particle size of drugs are important in the stability, dissolution, and processibility of drugs. Some commonly used methods in solid-state studies include microscopy, hot stage microscopy with polarized light, x-ray powder diffraction (XRPD), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), Fourier transform infrared FTIR/Raman, and solid-state NMR. 

It is important to characterize the physicochemical properties of the suspensions well, so that the PK data can be interpreted appropriately. Typical characterization of the drug substance includes purity, residual solvents, aqueous solubility pro Lie (pH 2, FaSSIF), crystallinity (XRPD/DSC), particle size, pl and logP. For solution formulations at various stages of discovery studies, dose analysis is essential, and for efLcacy assessment and toxicology studies, chemical stability for the... 

Quantitative and/or qualitative XRPD methods have been reported to determine the polymorphic content of clopidogrel bisulfate samples, and these have been summarized in Table 2.3. Koradia et al. [16] reported the qualitative analysis of clopidogrel bisulfate in both active pharmaceutical ingredients and tablet dosage forms. Based on the interplanar distances (d-spacing) associated with each polymorph, it was concluded that the molecular packing in Form-I was more dense than that of Form-II, indicating that Form-II would be less stable relative to Form-I. This result was similar with that reported by Bousquet [9]. 

Uvarov and Popov [20] reported the quantification of polymorphic forms I and II using two different XRPD methods. One method was based on the single peak intensity or direct method, and the second used whole-powder-pattern decomposition (WPPD) method. The Form-I nonoverlapping peaks suitable for analysis work were found at d-spacings 8.13, 5.98, and 4.32 A, while the useful peaks for Form-II had d-spacings of 7.24 and 6.88 A. It was shown that use of the WPPD method yielded better... 

In nature this common set is typically further restricted over wide geographic areas because of the influence or otherwise of soil-forming factors, the most important of which are parent material and degree of weathering. Thus, a typical sample of soil will contain a suite of around six to ten different major minerals. A major mineral may be defined as one that is present at a concentration of a few percent or more, at which it will be readily detectable by routine techniques such as x-ray provider diffraction (XRPD). It is also known as energy-dispersive x-ray analysis (EDXA) or energy-dispersive analysis of x-ray (EDAX) or microscopic examination, either optical or electron. It is also not uncommon for several other minerals to be present in any given soil but usually in amounts that put them below the routine detection limits of many techniques. Nonetheless, these accessory, or trace, minerals can often be concentrated by some means that separates the soil sample into different physical or chemical fractions. Such procedures effectively lower... 

Figure 11.7 X-ray diffraction equipment in capillary configuration showing from left to right Cu x-ray tube, monochromator to select Cu K-alpha radiation, sample mounted in capillary tube, beam tunnel, and X celerator position sensitive detector. The tube and the detector are scanned through a range of angles (theta) by the goniometer (the device in the background on which they are both mounted), and the XRPD is recorded and stored on a computer for subsequent analysis and processing.

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