Qualitative in situ analysis of multiple solid‐state forms using spectroscopy and partial least squares discriminant modeling

Kogermann, Karin; Aaltonen, Jaakko; Strachan, Clare J.; Pöllänen, Kati; Veski, Peep; Heinämäki, Jyrki; Yliruusi, Jouko; Rantanen, Jukka

doi:10.1002/jps.20840

Cited by 52 publications

(53 citation statements)

References 39 publications

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“…Crystalline polymorph in ethanol/water mixtures Raman spectroscopy Baclofen [127] Solution-mediated hydrate formation to baclofen monohydrate Wet granulation Raman spectroscopy Azithromycin [49] Hydrate formation to azithromycin monohydrate and dihydrate Storage experiments in a desiccator or humidity cell NIR spectroscopy Caffeine [128] Hydrate formation to a non-stoichiometric hydrate of caffeine, dehydrate formation Humidity cell NIR spectroscopy Risedronate sodium [129] Dehydrate formation of risedronate sodium hemi-pentahydrate Fluid-bed drying Raman spectroscopy Theophylline [130] Dehydrate formation of theophylline monohydrate Fluid-bed drying NIR and Raman spectroscopy Carbamazepine, piroxicam [131] Dehydrate formation of carbamazepine dihydrate and piroxicam monohydrate [82,135] Dehydrate formation of piroxicam monohydrate…”

Section: Raman Spectroscopymentioning

confidence: 99%

“…[134] In another work, the isothermal dehydration of piroxicam monohydrate and carbamazepine dihydrate was studied at different temperatures using hot-stage NIR and Raman spectroscopy combined with PLS discriminant analysis (PLS-DA) to qualitatively describe the solid-state transformations. [135] The PLS-DA models for NIR and Raman spectroscopy were constructed on the basis of the spectra of the pure solid-state forms of carbamazepine and piroxicam. In-situ monitoring of dehydration revealed insight into the dehydration processes and multiple solid-state forms that occur upon dehydration of carbamazepine dihydrate, while the removal of water from piroxicam monohydrate led to the formation of only crystalline form I (Figure 3).…”

Section: Raman Spectroscopymentioning

confidence: 99%

“…In a storage study, Raman spectroscopy was combined with XRPD to qualitatively analyse the spontaneous loss of crystallinity of various drugs in partially crystalline polyethylene oxide matrices stored at high humidity. The degree of crystallinity loss was related to the ability of each drug to dissolve in regions where the amorphous polymer and water [ 135] with permission from Wiley.…”

Section: Amorphous Formsmentioning

confidence: 99%

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Analysis of solid-state transformations of pharmaceutical compounds using vibrational spectroscopy

et al. 2009

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Objectives Solid-state transformations may occur during any stage of pharmaceutical processing and upon storage of a solid dosage form. Early detection and quantification of these transformations during the manufacture of solid dosage forms is important since the physical form of an active pharmaceutical ingredient can significantly influence its processing behaviour, including powder flow and compressibility, and biopharmaceutical properties such as solubility, dissolution rate and bioavailability. Key findings Vibrational spectroscopic techniques such as infrared, near-infrared, Raman and, most recently, terahertz pulsed spectroscopy have become popular for solidstate analysis since they are fast and non-destructive and allow solid-state changes to be probed at the molecular level. In particular, Raman and near-infrared spectroscopy, which require no sample preparation, are now commonly used coupled to fibreoptic probes and are able to characterise solid-state conversions in-line. Traditionally, uni-or bivariate approaches have been used to analyse spectroscopic data sets; however, recently the simultaneous detection of several solid-state forms has been increasingly performed using multivariate approaches where even overlapping spectral bands can be analysed. Summary This review discusses the applications of different vibrational spectroscopic techniques to detect and monitor solid-state transformations possible for crystalline polymorphs, hydrates and amorphous forms of pharmaceutical compounds. In this context, the theoretical basis of solid-state transformations and vibrational spectroscopy and common experimental approaches are described, including recent methods of data analysis.

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Section: Raman Spectroscopymentioning

confidence: 99%

Section: Raman Spectroscopymentioning

confidence: 99%

Section: Amorphous Formsmentioning

confidence: 99%

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Analysis of solid-state transformations of pharmaceutical compounds using vibrational spectroscopy

et al. 2009

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“…In such cases, the statistical analysis of in-line vibrational spectra is ultimately required (11,18,19). Further insight both into the API content and the structure in the solid state can be obtained by off-line methods, and X-ray scattering techniques are ideal for this purpose.…”

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Fast real-time monitoring of entacapone crystallization and characterization of polymorphs via Raman spectroscopy, statistics and SWAXS

Jednačak¹,

Hodžić²,

Scheibelhofer³

et al. 2014

Acta Pharmaceutica

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Many active pharmaceutical ingredients (APIs) are small organic molecules that have different polymorphic forms (1). It is well known that the API's polymorphic form can affect its physico-chemical properties, such as density, melting point, solubility, stability, morphology and bioavailability (2). Thus, polymorphic screening is a critical part of preformulation studies. The search for possible polymorphic forms typically begins with crystallization of a drug substance from various solvents, including those frequently used during the final crystallization steps (3, 4). Since the API's physicochemical properties can have a dramatic impact on its therapeutic effect, it is crucial to detect the polymorphic form with the characteristics appropriate for the intended use. For this purpose, the parameters affecting the crystallization process should be controlled and optimized (5). Major limitations to improving the control of crystallization parameters Crystallization of the drug entacapone from binary solvent mixtures was monitored in situ using a Raman optical probe. The recorded Raman spectra and statistical analysis, which included the principal components method and indirect hard modeling made it possible to estimate the starting point of crystallization, to assess crystallization temperatures and to provide information on the polymorphic content of the mixture. It was established that crystallization temperatures were proportional to the volume content of the solvent in mixtures. The samples were also evaluated off-line via Raman spectroscopy and SWAXS. The collected data showed the presence of forms b and g in all solvent mixtures. In a toluene/methanol 30:70 mixture, in addition to forms b and g, at least one of the forms A, D or a was also indicated by SWAXS. The results have shown that the presence of a particular polymorph is strongly dependent on the nature and portion of the solvent in the binary solvent mixture.

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“…Recently, vibrational spectroscopic analyses, such as Raman and near-infrared (NIR) spectroscopies, have been used for the same purpose as nondestructive measuring methods. [4][5][6][7] Terahertz (THz) spectroscopy has become popular as a novel technique to determine the crystallinity and polymorphism of drug substances. [8][9][10][11][12][13] The absorption spectrum of the THz region is largely affected by the intermolecular vibrations rather than the intramolecular vibrations.…”

mentioning

confidence: 99%

Chemical Mapping of Hydration and Dehydration Process of Theophylline in Tablets Using Terahertz Pulsed Imaging

Hisazumi

Suzuki

Wakiyama

et al. 2012

CHEMICAL & PHARMACEUTICAL BULLETIN

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The purpose of this research is to investigate the topographical pattern of hydration and dehydration (also known as pseudo-polymorphic change) of drug substance in drug product using terahertz (THz) pulsed imaging. Emphasis is placed on (1) applicability of THz pulsed imaging and (2) kinetic analysis in the pseudo-polymorphic change. Either anhydrous or monohydrated form of theophylline was used as the drug substance, leading to initially anhydrous or monohydrated tablets. These tablets were stored at 25°C to keep the relative humidity constant at 84% (anhydrous tablets) or 45% (monohydrated tablets), respectively. The THz pulsed imaging was confirmed to enable visualization that the hydration of the anhydrous form or the dehydration of the monohydrated form began on the surface of the tablets and gradually progressed to the core side in the tablets with storage. Kinetic studies indicated that these pseudo-polymorphic changes followed the phase boundary mechanism. Since the other imaging techniques has been scarcely achieved to show the topographical pattern of pseudo-polymorphic change of drug substances in drug products directly and visually, it is considered that THz pulsed imaging has a potential ability to solve complicated issues in pharmaceutical development.Key words terahertz pulsed imaging; theophylline; hydration; dehydration; polymorph; kinetic It is well known that many pharmaceutical solids can exist in more than one crystalline form as polymorphism. 1)Polymorphism also includes solvation or hydration products (also known as pseudo-polymorphs) and amorphous, 2) which generally have different physical and physicochemical properties. These may also affect the pharmaceutical properties of drug products, for example, difference in the dissolution rates and/or bioavailability.3) Polymorphic change may occur due to stress during the manufacturing process and storage. Since polymorphic change of drug substance in a drug product has the possibility to affect the safety and efficacy of the drug product, it is needed for detecting polymorphism in the drug product, to evaluate the impact of polymorphic change on the pharmaceutical properties. However, the evaluation often shows difficulty in detecting polymorphic change of drug substance in a drug product due to an interference of excipients.X-Ray powder diffraction (XRPD) method is the most popular technique for detecting and quantifying polymorphs. Recently, vibrational spectroscopic analyses, such as Raman and near-infrared (NIR) spectroscopies, have been used for the same purpose as nondestructive measuring methods. 4-7)Terahertz (THz) spectroscopy has become popular as a novel technique to determine the crystallinity and polymorphism of drug substances. [8][9][10][11][12][13] The absorption spectrum of the THz region is largely affected by the intermolecular vibrations rather than the intramolecular vibrations. Since the intermolecular vibration has a strong correlation with the molecular conformation (i.e., polymorphism), THz spectroscopy is considered...

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Qualitative in situ analysis of multiple solid‐state forms using spectroscopy and partial least squares discriminant modeling

Cited by 52 publications

References 39 publications

Analysis of solid-state transformations of pharmaceutical compounds using vibrational spectroscopy

Analysis of solid-state transformations of pharmaceutical compounds using vibrational spectroscopy

Fast real-time monitoring of entacapone crystallization and characterization of polymorphs via Raman spectroscopy, statistics and SWAXS

Chemical Mapping of Hydration and Dehydration Process of Theophylline in Tablets Using Terahertz Pulsed Imaging

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