Characterization of Mannitol Polymorphic Forms in Lyophilized Protein Formulations Using a Multivariate Curve Resolution (MCR)-Based Raman Spectroscopic Method

Xie, Yong; Cao, Wenjin; Krishnan, Sampathkumar; Lin, Hong; Cauchon, Nina S.

doi:10.1007/s11095-008-9624-1

Cited by 43 publications

(28 citation statements)

References 26 publications

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“…2.11(b). The spectrum from this region agrees well with that measured by Xie [104]. Surprisingly, there is a fifth component in the image, indicated by the cyan arrow and spectrum ( Fig.…”

Section: Mannitolsupporting

confidence: 88%

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Contrast in coherent Raman scattering microscopy

Garbacik

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“…2.11(b). The spectrum from this region agrees well with that measured by Xie [104]. Surprisingly, there is a fifth component in the image, indicated by the cyan arrow and spectrum ( Fig.…”

Section: Mannitolsupporting

confidence: 88%

“…Following the conventions of Xie et al [104] we refer to the three stable polymorphs, in descending order of thermodynamic stability, as the β, α, and δ forms. Each of these three crystal forms is reported to have a different vibrational spectrum for each orthogonal orientation of the crystal lattice.…”

Section: Mannitolmentioning

confidence: 99%

Contrast in coherent Raman scattering microscopy

Garbacik

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“…As several studies show (Xie et al, 2008;Cannon, Trappler, 2000), precise control of the process and the use of substances known as lyoprotectants, are critical to preserve the integrity of the product and to ensure its stability. Due to its properties as a bulking agent and lyoprotectant, mannitol is commonly used as an excipient in lyophilized pharmaceutical products.…”

Section: Introductionmentioning

confidence: 99%

Determination of moisture content in lyophilized mannitol through intact glass vials using NIR micro-spectrometers

Muzzio

Dini²,

Simionato

2011

Braz. J. Pharm. Sci.

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Determination of moisture content in lyophilized solids is fundamental to predict quality and stability of freeze-dried products, but conventional methods are time-consuming, invasive and destructive. The aim of this study was to develop and optimize a fast, inexpensive, noninvasive and nondestructive method for determination of moisture content in lyophilized mannitol, based on an NIR micro-spectrometer instead of a conventional NIR spectrometer. Measurements of lyophilized mannitol were performed through the bottom of rotating glass vials by means of a reflectance probe. The root mean standard error of prediction (RMSEP) and the correlation coefficient (R 2 pred ), yielded by the pre-treatments and calibration method proposed, was 0.233% (w/w) and 0.994, respectively.Uniterms: Near-infrared spectroscopy. Lyophilization. Multivariate analysis. Moisture content. Mannitol. Micro-spectrometer.A determinação do conteúdo de umidade em sólidos liofilizados é fundamental para se prever a qualidade e a estabilidade de produtos liofilizados, mas os métodos convencionais consomem muito tempo, são invasivos e destrutivos. O objetivo desse estudo foi desenvolver e otimizar um método rápido, econômico, não invasivo e não destrutivo para a determinação do conteúdo de umidade em manitol liofilizado, com base em microespectrômetro de infravermelho próximo ao invés de um espectrômetro de infravermelho próximo convencional. As medidas de manitol liofilizado foram realizadas através do fundo de recipiente de vidro em rotação por meio de sonda de reflectância. A raíz do erro médio padrão de predição (RMSEP) e o coeficiente de correlação (R 2 pred ) obtidos pelo prétratamento e pelo método de calibração proposto foram, respectivamente, 0,233% (p/p) e 0,994. Uniterms: Espectroscopia de infravermelho próximo. Liofilização. Análise multivariada. Análise de unidade. Manitol. Microespectrômetro.

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“…When in combination with multivariate analysis methods, such as principal component analysis (PCA) and partial least squares (PLS), Raman spectroscopy can be used not only for qualitative identification of the entity being measured but also for semiquantitative and quantitative analysis. [3,4] Due to the wealth of chemical and physical information available in Raman spectroscopy, its applications have expanded to polymorph monitoring, [5,6] intermediate detection, [7] crystallization progression for drug substances, [8] content uniformity, [3,9] coating thickness, [10] and end-point determination for drug product processes. [11,12] As a rapid, non-invasive, non-destructive method of analysis, it is suitable for a variety of pharmaceutical dosage forms, such as solids, [12 -14] topical gels and emulsions, [15] dry powder inhalers [4] and suspensions.…”

Section: Introductionmentioning

confidence: 99%

Real‐time monitoring of active ingredient dispersion in a pharmaceutical aqueous suspension using Raman spectroscopy

Medendorp

Yonzon

2011

J Raman Spectroscopy

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In a typical aqueous nasal suspension manufacturing process, the homogeneity of the active pharmaceutical ingredient (API) dispersion in a premix vessel is determined merely by visual observation. In this study, to better demonstrate in-process control, Raman spectroscopy was developed as a process analytical tool (PAT) to monitor the real-time API dispersion homogeneity in the active premix process. The end-point variations of the API dispersion as a function of the surfactant type, surfactant concentration, and agitation speed were evaluated by dispersive Raman spectroscopy in combination with multivariate analysis for both lab-scale and pilot-scale batches. The optimal surfactant concentration and type were determined to be 0.2% surfactant A for the active dispersion based on a quantitative end-point comparison. In addition, a chemometric model was developed successfully for the real-time prediction of API concentration in the active premix, with a root mean squared error of prediction (RMSEP) of 5.4%. In conclusion, Raman spectroscopy has proven to be a viable PAT tool to qualitatively and quantitatively assess the active premix homogeneity in an aqueous nasal suspension manufacturing process. In the future, this method can potentially be used in the commercial manufacturing process for in-process control of the dispersion homogeneity of the suspension.

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Characterization of Mannitol Polymorphic Forms in Lyophilized Protein Formulations Using a Multivariate Curve Resolution (MCR)-Based Raman Spectroscopic Method

Abstract: An MCR-Raman method has been developed for the quantitative determination of five different mannitol polymorphic forms in the presence of sucrose and protein.

Cited by 43 publications

References 26 publications

Contrast in coherent Raman scattering microscopy

Contrast in coherent Raman scattering microscopy

Determination of moisture content in lyophilized mannitol through intact glass vials using NIR micro-spectrometers

Real‐time monitoring of active ingredient dispersion in a pharmaceutical aqueous suspension using Raman spectroscopy

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