Quantitative Determination of Hydrate Content of Theophylline Powder by Chemometric X-ray Powder Diffraction Analysis

We propose an approach for the simultaneous determination of multiple components in pharmaceutical mixed powder based on powder X-ray diffraction (PXRD) method coupled with chemometrics. Caffeine anhydrate, acetaminophen and lactose monohydrate were mixed at various ratios. The samples were analyzed by PXRD method in the ranges of 2θ 5.00-30.0 and 35.0-45.0 degrees. Obtained diffractograms were analyzed by conventional peak intensity method, multi curve resolution (MCR)-alternating least squares (ALS) method and partial least squares (PLS) method. Constructed PLS models can most accurately predict the concentrations among different methods used. Each regression vector of PLS correlates not only to the compound of interest but also to the coexisting compounds. The combination of PXRD and PLS methods is concluded to be powerful approach for analyzing multi components in pharmaceutical formulations.Key words powder X-ray diffraction; partial least square; pharmaceutical formulationThe polymorphs and pseudo-polymorphs (hydrates and solvates) of pharmaceuticals exhibit different physicochemical properties such as solubility, dissolution rate, stability and hygroscopicity. These properties strongly relate to the pharmaceutical properties in their dosage forms such as specific bioavailability, efficacy, stability and toxicity.1) Pharmaceutical regulations are, therefore, required for producing appropriate bulk drugs, the crystalline modifications of which (i.e., polymorphism) are well specified or precisely controlled. 2)Powder X-ray diffraction (PXRD) analysis is the most frequently used method for identifying crystalline modifications and for determining their contents in bulk powders.3) Any crystals have their own PXRD patterns. Pharmaceutical formulations are, in general, composed of multiple components including excipients. PXRD is, therefore, useful to identify crystalline compounds in the formulation and to determine their amounts in a non-contact and non-destructive fashion. 4,5) However, PXRD method has large relative errors, typically around ±5%. Such shortcoming of PXRD method is serious when two or more components having broad and overlapping X-ray diffraction peaks are contained in one formulation.Regulatory authorities such as the U.S. Food and Drug Administration and the International Conference on Harmonization have requested to use Process Analytical Technology (PAT) in order to reduce the production risk of inferior pharmaceuticals.6) Since the introduction of guidelines for PAT, online and real-time analysis have increasingly been accepted in pharmaceutical industry as a tool for monitoring and controlling manufacturing process. Non-contact methods, such as PXRD analysis, near infrared (NIR) spectroscopy and terahertz spectroscopy have been paid attention as important tools for PAT. 6) Chemoinformatics are employed by pre-formulation scientists for the quantitative and qualitative analyses of NIR because they can provide ideal means for extracting quantitative information from complex spectra of mult...

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“…Otsuka and Kinoshita 13) applied PLS to PXRD patterns and constructed an accurate calibration model for theophylline hydrate.…”

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confidence: 99%

Quantification of Pharmaceutical Compounds Based on Powder X-Ray Diffraction with Chemometrics

Otsuka

Itô

Matsumura

et al. 2016

CHEMICAL & PHARMACEUTICAL BULLETIN

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“…Powder XRD identifies hydrates through peaks associated with the hydrate structure, which is different from the anhydrous material and also from other hydrates with a different stoichiometric ratio. The technique is qualitative in general, although a suitable sample preparation and a careful analysis can yield quantitative information as well. − NIR, often in conjunction with Raman spectroscopy, is also popular. , Here vibrational modes of the molecules in a hydrate and anhydrate can be distinguished, as hydrates include additional features, mainly the O–H vibrational modes which are detected by NIR. The method is again qualitative in general, although it can provide quantitative information, but since the NIR spectrum is a convolution of chemical and physical interactions between the sample and NIR radiation, the level of detection and precision will depend very much on the spectral characteristics of the components and on the sampling technique. , …”

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confidence: 99%

Quantitative Analysis of Hydration Using Nitrogen-14 Nuclear Quadrupole Resonance

Gregorovič

2015

Anal. Chem.

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Hydration is a quite common process in pharmaceutical solids. Sometimes it is desirable, as it stabilizes the crystal structure; in other cases it is unwanted, as it changes the physical and chemical properties of drugs. We here use (14)N NQR spectroscopy to quantitatively analyze hydration of a model compound, 5-aminotetrazole. (14)N NQR has some great advantages compared to other routinely used techniques to study hydration, like a very simple spectrum, single point calibration, and no need for special sample preparation, but the method's great disadvantage is a rather small sensitivity. Nevertheless, here we demonstrate that (14)N NQR, although being significantly less sensitive than XRD, NIR, and also (35)Cl NQR, is still capable of providing excellent quantitative accuracies. We can achieve errors <1% of the total amount, provided good temperature stabilization is implemented, which then allows long experimental times. We also present results obtained with a SLSE pulse sequence, which is a less robust approach but allows the use of much shorter measuring times (∼200×) and could be used for quantitative real time monitoring of hydration or dehydration.

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“…THM content in the standard samples was evaluated based on XRPD profiles by the diffraction peak height and area methods and the Wakelin's and principal component regression (PCR) methods. In the result based on validation XRPD datasets, the order of the mean bias and the mean accuracy was peak height > peak area > Wakelin's > PCR, indicating that PCR was the best method to correct sample crystal orientation [76].…”

Section: Tablet Parametricmentioning

confidence: 96%

Pharmaceutical Applications of Chemometric Techniques

Singh

Juneja

Kaur

et al. 2013

ISRN Analytical Chemistry

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Chemometrics involves application of various statistical methods for drawing vital information from various manufacturing-related processes. Multiway chemometric models like parallel factor analysis (PARAFAC), Tucker-3, N-partial least square (N-PLS), and bilinear models like principle component regression (PCR) and partial least squares (PLS) have been discussed in the paper. Chemometric approaches can be used to analyze the data obtained from various instruments including near infrared (NIR), attenuated total reflectance Fourier transform infrared (ATR-FTIR), high-performance liquid chromatography (HPLC), and terahertz pulse spectroscopy. The technique has been used in the quality assurance and quality control of pharmaceutical solid dosage forms. Moreover, application of chemometric methods in the evaluation of properties of pharmaceutical powders and tablet parametric tests has also been discussed in the review. It has been suggested as a useful method for the real-time in-process testing and is a valuable process analytical tool.

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Quantitative Determination of Hydrate Content of Theophylline Powder by Chemometric X-ray Powder Diffraction Analysis

Cited by 14 publications

References 16 publications

Quantification of Pharmaceutical Compounds Based on Powder X-Ray Diffraction with Chemometrics

Quantification of Pharmaceutical Compounds Based on Powder X-Ray Diffraction with Chemometrics

Quantitative Analysis of Hydration Using Nitrogen-14 Nuclear Quadrupole Resonance

Pharmaceutical Applications of Chemometric Techniques

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