Quality by Design, Part I: Application of NIR Spectroscopy to Monitor Tablet Manufacturing Process

Tabasi, Simin Hassannejad; Fahmy, Raafat; Bensley, Dennis; O'Brien, Charles; Hoag, Stephen W.

doi:10.1002/jps.21303

Cited by 58 publications

(20 citation statements)

References 26 publications

(21 reference statements)

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“…The use of NIR has found increasing pharmaceutical analysis applications for the identification and quality testing of raw materials (2,3), monitoring of blending (4,5), roller compaction (5,6), and fluid-bed granulation and drying operations (7)(8)(9). It has also been used as a nondestructive technique to monitor tablet (10) and tablet-coating (11) manufacturing processes. NIR has been used to determine drug product authenticity (12).…”

Section: Introductionmentioning

confidence: 99%

Inline Real-Time Near-Infrared Granule Moisture Measurements of a Continuous Granulation–Drying–Milling Process

et al. 2011

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Abstract. The purpose of this research was to use inline real-time near-infrared (NIR) to measure the moisture content of granules manufactured using a commercial production scale continuous twin-screw granulator fluid-bed dryer milling process. A central composite response surface statistical design was used to study the effect of inlet air temperature and dew point on granule moisture content. The NIR moisture content was compared to Karl Fischer (KF) and loss on drying (LOD) moisture determinations. Using multivariate analysis, the data showed a statistically significant correlation between the conventional methods and NIR. The R 2 values for predicted moisture content by NIR versus KF and predicted moisture values by NIR versus LOD were 0.94 (p<0.00001) and 0.85 (p<0.0002), respectively. The adjusted R 2 for KF versus LOD correlation was 0.85 (p<0.0001). Analysis of the response surface design data showed that inlet air temperature over a range of 35-55°C had a significant linear impact on granule moisture content as measured by predicted NIR (adjusted R 2 =0.84, p<0.02), KF (adjusted R 2 =0.91, p<0.0001), and LOD (adjusted R 2 =0.85, p<0.0006). The inlet air dew point range of 10-20°C did not have a significant impact on any of the moisture measurements.

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Section: Introductionmentioning

confidence: 99%

Inline Real-Time Near-Infrared Granule Moisture Measurements of a Continuous Granulation–Drying–Milling Process

et al. 2011

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“…Some monitoring techniques in the tableting process with diffuse reflectance NIR spectroscopy have actually been reported. 5,6) Variations in the physical properties of sample generally affect the spectra when diffuse transmission or reflectance NIR spectroscopy is used. 7,8) Especially, the difference in tablet density is shown as a baseline shift in the spectra, 9) leading to an issue that should be solved because this effect complicates the quantification.…”

Section: -4)mentioning

confidence: 99%

Using Terahertz Reflectance Spectroscopy to Quantify Drug Substance in Tablets

Hisazumi

Watanabe

Suzuki

et al. 2012

CHEMICAL & PHARMACEUTICAL BULLETIN

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The purpose of this research is to investigate the applicability of terahertz (THz) reflectance spectroscopy for quantification of drug substance in tablets, so as to demonstrate the feasibility for applying this technique to tableting process monitoring. In order to acquire a suitable absorbance spectrum for this purpose, it was necessary to enhance the reflection intensity. By using an aluminum plate as a mirror at the opposite surface of the tablet, a reasonable absorbance spectrum could be acquired to reflect the bulk information of the tablet. To assess the limit of tablet thickness, linearity between the tablet thickness and the absorbance value was investigated using lactose and mannitol tablets. Since linearity was found within 0.75-5.0 mm for both tablets using 0.4 and 0.8 THz region, it was confirmed that THz reflectance spectroscopy is applicable to tablets within at least 5.0 mm thickness. Mannitol tablets containing sodium salicylate as the model drug substance were used to investigate the quantitative performance of this technique. It was confirmed that the established calibration model was acceptable for this quantification because of the root-mean-squared error of cross-validation (RMSECV) being 1.95%. In order to evaluate the applicability of this technique, content quantitative performance in double layered tablets having active and placebo layers were assessed. Since this calibration model achieved the root-mean-squared error of prediction (RMSEP) of 1.42% for the double layered tablets, this technique was considered feasible even if the drug substance is localized in the tablets.Key words terahertz; reflection; in-line monitoring; process analytical technology; tablet; sodium salicylateThe tablet is one of the popular dosage forms in pharmaceutics, and quantification of drug substance in drug product, including the content uniformity test, is a critical and mandatory quality assurance requirement in tablet manufacturing. Although a conventional HPLC method is the most popular technique for quantification, there are growing interests to examine alternative analytical techniques that are possible to measure drug products in-process with a nondestructive manner. These interests are also in line with the United States Food and Drug Administration (FDA) Process Analytical Technology (PAT) initiative and guidelines.1) As a well-known example of the alternative techniques, near infrared (NIR) spectroscopy is being extensively used for the quantification of drug substance as a PAT tool. 2-4)Typically, only 10-30 tablets are generally employed as the representative for batch manufacturing of several million tablets. In-line monitoring during the tableting process is expected to attain higher quality assurance than the traditional end-product testing, because quantification for each and every unit dose would be expected. A reflectance spectroscopy is usually employed as the in-line monitoring tool, because a detector of a transmission spectrometer cannot be installed into a rotary tableting machine to ...

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“…particle size growing during granulation or the water content in the granule (Räsänen & Sandler, 2007;Rantanen 2007). NIR is also used for monitoring the final quality of the single tablets, because it is possible to quantify the active ingredient in a none-destructive manner (Tabasi et al, 2008), and can be applied to indentify counterfeit drugs (Rodionova et al, 2005). Another example is the prediction of tablet hardness based on NIR spectra of powders with lubricants (Otsuka & Yamane, 2006.…”

Section: Molecular Vibrational Spectroscopy Techniques Such As Inframentioning

confidence: 99%

Chemometrics (PCA) in Pharmaceutics: Tablet Development, Manufacturing and Quality Assurance

Tho¹,

Bauer‐Brandl²

2012

Principal Component Analysis - Multidisciplinary Applications

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Quality by Design, Part I: Application of NIR Spectroscopy to Monitor Tablet Manufacturing Process

Cited by 58 publications

References 26 publications

Inline Real-Time Near-Infrared Granule Moisture Measurements of a Continuous Granulation–Drying–Milling Process

Inline Real-Time Near-Infrared Granule Moisture Measurements of a Continuous Granulation–Drying–Milling Process

Using Terahertz Reflectance Spectroscopy to Quantify Drug Substance in Tablets

Chemometrics (PCA) in Pharmaceutics: Tablet Development, Manufacturing and Quality Assurance

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