In Situ Raman Spectroscopy for In-Line Control of Pharmaceutical Crystallization and Solids Elaboration Processes: A Review

Févotte, Gilles

doi:10.1205/cherd06229

Cited by 132 publications

(84 citation statements)

References 81 publications

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“…Chemical reactions, wet granulation, dissolution, polymorphism and crystallization processes have already been investigated via in situ or in-line vibrational spectroscopy (6)(7)(8)(9)(10)(11). Raman and infrared spectroscopy have been employed to investigate pharmaceutical crystal forms (2,4,12).…”

mentioning

confidence: 99%

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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mentioning

confidence: 99%

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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“…For example, NIR spectroscopy has been widely used for online/at-line analysis of solid dosage drug product in manufacturing (8)(9)(10)(11). A number of publications have shown the use of Raman for in-process monitoring and control during both drug substance and product manufacturing (8,(12)(13)(14). However, to our knowledge, no applications have been reported on using in-line spectroscopy tools to support manufacturing of SGC products.…”

Section: Introductionmentioning

confidence: 99%

“…Raman spectroscopy has been found in a wide array of applications in the pharmaceutical industry, including inprocess monitoring of various processes such as synthetic organic reactions, API crystallization, granulation and coating (12,24,29,30). The high specificity of Raman spectral features makes it a suitable tool for analyzing multi-component systems both qualitatively and quantitatively.…”

Section: Introductionmentioning

confidence: 99%

In-line ATR-UV and Raman Spectroscopy for Monitoring API Dissolution Process During Liquid-Filled Soft-Gelatin Capsule Manufacturing

Wan

Zordan

et al. 2015

AAPS PharmSciTech

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Abstract. Complete dissolution of the active pharmaceutical ingredient (API) is critical in the manufacturing of liquid-filled soft-gelatin capsules (SGC). Attenuated total reflectance UV spectroscopy (ATR-UV) and Raman spectroscopy have been investigated for in-line monitoring of API dissolution during manufacturing of an SGC product. Calibration models have been developed with both techniques for in-line determination of API potency. Performance of both techniques was evaluated and compared. The ATR-UV methodology was found to be able to monitor the dissolution process and determine the endpoint, but was sensitive to temperature variations. The Raman technique was also capable of effectively monitoring the process and was more robust to the temperature variation and process perturbations by using an excipient peak for internal correction. Different data preprocessing methodologies were explored in an attempt to improve method performance.

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“…Although XRD is the benchmark method for studying crystallinity (3,4), both the single crystal and PXRD techniques are technologies which are best suited to off-line analysis. The emerging reliance on process analytical technologies has led to an increase use of the optical spectroscopies such as near infrared (NIR), Raman spectroscopy, and THz spectroscopy which offer a potential solution for on-line freeze-drying process control (2,5).…”

Section: Introductionmentioning

confidence: 99%

Characterisation of Crystalline-Amorphous Blends of Sucrose with Terahertz-Pulsed Spectroscopy: the Development of a Prediction Technique for Estimating the Degree of Crystallinity with Partial Least Squares Regression

2013

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Abstract. The control of the amorphous and crystalline states of drugs and excipients is important in many instances of product formulation, manufacture, and packaging, such as the formulation of certain (freezedried) fast melt tablets. This study examines the use of terahertz-pulsed spectroscopy (TPS) coupled with two different data analytical methods as an off-line tool (in the first instance) for assessing the degree of crystallinity in a binary mixture of amorphous and polycrystalline sucrose. The terahertz spectrum of sucrose was recorded in the wave number range between 3 and 100 cm −1 for both the pure crystalline form and for a mixture of the crystalline and amorphous (freeze-dried) form. The THz spectra of crystalline sucrose showed distinct absorption bands at ∼48, ∼55, and ∼60 cm −1 while all these features were absent in the amorphous sucrose. Calibration models were constructed based on (1) peak area analysis and (2) partial least square regression analysis, with the latter giving the best LOD and LOQ of 0.76% and 2.3%, respectively. The potential for using THz spectroscopy, as a quantitative in-line tool for percent crystallinity in a range of complex systems such as conventional tablets and freeze-dried formulations, is suggested in this study.

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In Situ Raman Spectroscopy for In-Line Control of Pharmaceutical Crystallization and Solids Elaboration Processes: A Review

Cited by 132 publications

References 81 publications

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

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

In-line ATR-UV and Raman Spectroscopy for Monitoring API Dissolution Process During Liquid-Filled Soft-Gelatin Capsule Manufacturing

Characterisation of Crystalline-Amorphous Blends of Sucrose with Terahertz-Pulsed Spectroscopy: the Development of a Prediction Technique for Estimating the Degree of Crystallinity with Partial Least Squares Regression

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