Process Optimization of a Complex Pharmaceutical Polymorphic System via In Situ Raman Spectroscopy

Starbuck, Cíndy; Spartalis, Angela; Wai, L.; Wang, Jian; Fernandez, Paul; Lindemann, Christopher M.; Zhou, Guangya; Ge, Zigang

doi:10.1021/cg025559k

Cited by 95 publications

(83 citation statements)

References 17 publications

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“…For instance, the polymorphic conversions of the compound MK-A, which is known to exist in several anhydrous forms as well as a hemihydrate and dihydrate form, have been described using in-situ Raman spectroscopy. [86] PLS regression based on binary mixtures of two polymorphic forms was used to quantify solidstate conversions and determine conversion kinetics as well as pathways that are likely to occur during manufacturing of polymorphic form A in isopropyl acetate slurries. The effects of seeding with a polymorphic form or adding water were also investigated and in-situ Raman spectroscopy was found to be a useful tool for process development in terms of finding an optimal temperature for the preparation of the desired polymorphic form.…”

Section: Raman Spectroscopymentioning

confidence: 99%

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%

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

et al. 2009

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“…In the pharmaceutical industry, identification of pseudopolymorphs of APIs during their early stage development is critical (Byrn et al, 1995;Starbuck et al, 2002;Dahiya and Gautam, 2011;Fan and Luo, 2011;Ding et al, 2011). In addition, the study on the solventmediated transformation between pseudopolymorphs is highly important as well.…”

Section: Introductionmentioning

confidence: 99%

Characterization and pseudopolymorphism of l-phenylalanine anhydrous and monohydrate forms

Lü¹,

Wang²,

Li³

et al. 2012

Afr. J. Pharm. Pharmacol.

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In this work, the preformulation study on the solid state characterization for the anhydrous form and the monohydrate form of L-phenylalanine has been initially conducted by the use of powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and microscopy. Meanwhile, the solubility of both forms and the transformation kinetics from anhydrous form to monohydrate form in different water/acetone mixtures were studied as well. The transformation rate can be prohibited by increasing temperature and reducing water content in the solvent mixtures. These results will contribute to a better understanding of drugs' pseudopolymorphism for pharmaceutical industry.

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“…[9][10][11][12][13][14][15][16][17] Despite the similar information content of Raman and infrared absorption (IR) spectroscopies, Raman presents several advantages over IR. In the particular context of the present work, the most relevant advantage is the low Raman activity of water vibrations, whose strong infrared activity tends to mask a wide IR spectrum range.…”

Section: Introductionmentioning

confidence: 99%

Probing Pseudopolymorphic Transitions in Pharmaceutical Solids using Raman Spectroscopy: Hydration and Dehydration of Theophylline

Amado

Nolasco

Ribeiro‐Claro

2007

Journal of Pharmaceutical Sciences

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Theophylline is known to undergo vapor phase induced hydrate-anhydrate pseudopolymorphic transformations, which can affect its bioavailability. In this work, the kinetics of the pseudopolymorphic transitions of theophylline crystals in different storage conditions is studied using a vibrational spectroscopic technique. While the hydration is a single-step process with a half-life time of ca. 5 h, the dehydration occurs through a two-step mechanism. In addition, the phase stability of hydrate-anhydrate systems in different relative humidity (RH) conditions was probed. The critical RH for anhydrous teophylline was found to be at ca. 79%, while the critical RH for dehydration is ca. 30%. ß

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Process Optimization of a Complex Pharmaceutical Polymorphic System via In Situ Raman Spectroscopy

Cited by 95 publications

References 17 publications

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

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

Characterization and pseudopolymorphism of l-phenylalanine anhydrous and monohydrate forms

Probing Pseudopolymorphic Transitions in Pharmaceutical Solids using Raman Spectroscopy: Hydration and Dehydration of Theophylline

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