Tablet CU Analysis and Spray-Coating Process Monitoring by Antaris FT-NIR Analyzer

Herman He, Thermo Fisher Scientifi c, Lanham, MD USA

2 Tablet CU Analysis and Spray-Coating Process Monitoring by Antaris FT-NIR Analyzer

Tablet CU Analysis and Spray-Coating Process Monitoring

by Antaris FT-NIR Analyzer Herman He, Ph.D.

Thermo Fisher Scientific, Lanham, Maryland, USA

Overview Tablets and capsules are the most common form of commercially available pharmaceutical products. Fourier transformed near-infrared (FT-NIR) analysis is a powerful technique to measure these materials. The advantages of using both diffuse reflectancemeasurement and transmission measurement on the Thermo Scientific Antaris™ FT-NIR analyzer will be discussed in thispresentation. This presentation also shows an example of PAT application to monitor tablet spray coating process. Because of thefast measurement speed of the FT-NIR analyzer, process operators now have the ability to estimate the coating time, and they areable to fine-tune process parameters in order to optimize the coating process to achieve better consistency in product quality.

IntroductionAPI dosage analysis and content uniformity analysis of pharmaceutical solid dosage forms is normally done by HPLC, which requirestedious sample preparation and recycling of hazardous solvents. Pharmaceutical companies are interested in easier techniques thatwould increase the number of samples per batch to allow representative trending studies and to improve quality control of tabletproduction. For these reasons, FT-NIR analysis is an appealing alternative because of its faster analysis speed. Although most tabletanalysis is conducted using diffuse reflectance, increased concerns about content uniformity have led to the desire to examine othernondestructive methods like transmission that can sample a more representative bulk volume of the tablet. Since the NIR beam canilluminate the whole tablet and travel a much longer distance, this transmission technique allows us to detect the API inside the coreof tablets and provide more representative data.

Experimental Setup Diffuse reflectance and transmission spectra were acquired on the Thermo Scientific Antaris FT-NIR Method Development SamplingSystem (Figure 1). Tablets were analyzed using the tablet detector and integrating sphere modules to allow both transmission andreflection sampling without moving the samples. Reflectance sampling parameters were 64 scans per tablet at 8 cm-1 resolution from4000 to 10000 cm-1 for the reflectance and . 6000 to 12000 cm-1 for the transmission measurement . The Standard Tablet detectorswere used for the transmission study. The diffuse reflectance spectra were measured with the integrating sphere using the internalgold flag as the background.

Summary

The spectroscopy techniques used in laboratories to obtain deep scientific and engineering understandings of products and processesare now available to the pharmaceutical industry and encouraged by the PAT initiative. This poster has illustrated how a single analyticaltechnique, FT-NIR, can be used to gain insights in a particular product or process and to gain a degree of control over a process bysimply measuring the API or CUI of tablets and making a set of process decisions for the tablet coating processes. Even though manyother spectroscopic techniques, such as Raman and UV-Vis, are available to scientists and engineers for to analyze different propertiesof products, the robustness of instrumentation, speed of analysis, and ease of use makes FT-NIR the top choice within the PAT initiativeto create scientific and engineering knowledge, a fact well established in the research community and growing in acceptance within thepharmaceutical industry.

Spectral Data Processing and PLS modeling

Both reflectance spectral and transmittance spectral data were processed first with Norris second derivative to remove spectralbaseline shift due to the light scattering from tablet samples, then with SNV (standard normal variant) in order to reduce the variation inpenetration distance or path length. The number of PLS model factors were decided by the leave-one-out cross validation method.

FIGURE 1. Antaris II MDS FT-NIR Analyzer

Transmission

Diffuse Reflection

FIGURE 2. Tablet Reflectance Spectral Analysis

CaffeineRMSEC: 0.781 Corr. Coeff.: 0.9713RMSEP: 0.830 Corr. Coeff.: 0.94963 factors used

CalibrationValidationCorrectionCross-correctionIgnore

-0 15Actual

-015

Calcu

late

d

PAT Application: at-line spay coating analysis

Many tablets today are coated after being pressed. Modern tablet coatings are polymer and polysaccharide based, with plasticizer andpigments included as well. Coatings are necessary for tablets that have an unpleasant taste and some coating formulations evencontain API that help to achieve certain functions of drug delivery. Tablet coatings are also useful to extend the shelf-life of componentsthat are sensitive to moisture or oxidation. Since spray coating is a very time sensitive process, a fast in-line or at-line measurement isneeded to control product quality and to avoid over-coating. Figure 4 shows an application of an Antaris MX FT-NIR analyzer with adiffuse reflectance probe installed in a Perfima 200 for the coating weight monitoring, while Figure 5 illustrates an example of at-linecoating analysis with an Antaris II FT-NIR with an autosampler.

FIGURE 3. Tablet Transmission Spectral Analysis

ASARMSEC: 1.75 Corr. Coeff.: 0.9885RMSEP: 2.16 Corr. Coeff.: 0.99357 factors used

CalibrationValidationCorrectionCross-correctionIgnore

58 102Actual

5810

2C

alcu

late

d

Coating Time (hour)

Coa

ting

Dos

age

(%)

100

80

60

40

20

1 2 3 4 5 6 7

T T

FIGURE 5. At-line Coating Process Monitoring with an Antaris II FT-NIR Analyzer and An Autosampler

APIRMSEC: 2.82 Corr. Coeff.: 0.9938RMSEP: 3.845 factors used

CalibrationValidationCorrectionCross-correctionIgnore

42 146Actual

4214

6C

alcu

late

d

Result and DiscussionTransmission and reflectance measurements were attempted for the same set of tablets, and both measurements showed a verystrong correlation with the API. Since the reflectance signal from a tablet is mostly from the tablet surface, the scanned sample is only aportion of the entire tablet. Unless a tablet is uncoated and very uniform, the standard deviation of tablet reflectance measurement isusually larger than the traditional HPLC method.

The NIR beam illuminates almost the entire tablet during the transmission measurement, and the equivalent path length is much longerthan the tablet thickness. The accuracy of the tablet transmission measurement is typically compatible with the HPLC technique but inmuch fast speed. However, this transmission technique is limited by the tablet thickness.

FIGURE 4. In-line Coating Process Monitoring with Antaris MX FT-NIR Analyzer and A Diffuse Reflectance Probe

0.40

0.45

0.50

0.55

0.60

0.65

0.70

0.75

0.80

0.85

0.90

0.95

1.00

1.05

1.10

1.15

1.20

1.25

Abs

5000 6000 7000 8000 9000 10000 cm-1

Before coating

Opadry 7185cm-1

0.40

0.45

0.50

0.55

0.60

0.65

0.70

0.75

0.80

0.85

0.90

0.95

1.00

1.05

1.10

1.15

1.20

1.25

Abs

5000 6000 7000 8000 9000 10000 cm-1

After coating

3Thermo Scienti� c Poster Note • EAS13_He_E 11/13S

Tablet CU Analysis and Spray-Coating Process Monitoring

by Antaris FT-NIR Analyzer Herman He, Ph.D.

Thermo Fisher Scientific, Lanham, Maryland, USA

Overview Tablets and capsules are the most common form of commercially available pharmaceutical products. Fourier transformed near-infrared (FT-NIR) analysis is a powerful technique to measure these materials. The advantages of using both diffuse reflectancemeasurement and transmission measurement on the Thermo Scientific Antaris™ FT-NIR analyzer will be discussed in thispresentation. This presentation also shows an example of PAT application to monitor tablet spray coating process. Because of thefast measurement speed of the FT-NIR analyzer, process operators now have the ability to estimate the coating time, and they areable to fine-tune process parameters in order to optimize the coating process to achieve better consistency in product quality.

IntroductionAPI dosage analysis and content uniformity analysis of pharmaceutical solid dosage forms is normally done by HPLC, which requirestedious sample preparation and recycling of hazardous solvents. Pharmaceutical companies are interested in easier techniques thatwould increase the number of samples per batch to allow representative trending studies and to improve quality control of tabletproduction. For these reasons, FT-NIR analysis is an appealing alternative because of its faster analysis speed. Although most tabletanalysis is conducted using diffuse reflectance, increased concerns about content uniformity have led to the desire to examine othernondestructive methods like transmission that can sample a more representative bulk volume of the tablet. Since the NIR beam canilluminate the whole tablet and travel a much longer distance, this transmission technique allows us to detect the API inside the coreof tablets and provide more representative data.

Experimental Setup Diffuse reflectance and transmission spectra were acquired on the Thermo Scientific Antaris FT-NIR Method Development SamplingSystem (Figure 1). Tablets were analyzed using the tablet detector and integrating sphere modules to allow both transmission andreflection sampling without moving the samples. Reflectance sampling parameters were 64 scans per tablet at 8 cm-1 resolution from4000 to 10000 cm-1 for the reflectance and . 6000 to 12000 cm-1 for the transmission measurement . The Standard Tablet detectorswere used for the transmission study. The diffuse reflectance spectra were measured with the integrating sphere using the internalgold flag as the background.

Summary

The spectroscopy techniques used in laboratories to obtain deep scientific and engineering understandings of products and processesare now available to the pharmaceutical industry and encouraged by the PAT initiative. This poster has illustrated how a single analyticaltechnique, FT-NIR, can be used to gain insights in a particular product or process and to gain a degree of control over a process bysimply measuring the API or CUI of tablets and making a set of process decisions for the tablet coating processes. Even though manyother spectroscopic techniques, such as Raman and UV-Vis, are available to scientists and engineers for to analyze different propertiesof products, the robustness of instrumentation, speed of analysis, and ease of use makes FT-NIR the top choice within the PAT initiativeto create scientific and engineering knowledge, a fact well established in the research community and growing in acceptance within thepharmaceutical industry.

Spectral Data Processing and PLS modeling

Both reflectance spectral and transmittance spectral data were processed first with Norris second derivative to remove spectralbaseline shift due to the light scattering from tablet samples, then with SNV (standard normal variant) in order to reduce the variation inpenetration distance or path length. The number of PLS model factors were decided by the leave-one-out cross validation method.

FIGURE 1. Antaris II MDS FT-NIR Analyzer

Transmission

Diffuse Reflection

FIGURE 2. Tablet Reflectance Spectral Analysis

CaffeineRMSEC: 0.781 Corr. Coeff.: 0.9713RMSEP: 0.830 Corr. Coeff.: 0.94963 factors used

CalibrationValidationCorrectionCross-correctionIgnore

-0 15Actual

-015

Calcu

late

d

PAT Application: at-line spay coating analysis

Many tablets today are coated after being pressed. Modern tablet coatings are polymer and polysaccharide based, with plasticizer andpigments included as well. Coatings are necessary for tablets that have an unpleasant taste and some coating formulations evencontain API that help to achieve certain functions of drug delivery. Tablet coatings are also useful to extend the shelf-life of componentsthat are sensitive to moisture or oxidation. Since spray coating is a very time sensitive process, a fast in-line or at-line measurement isneeded to control product quality and to avoid over-coating. Figure 4 shows an application of an Antaris MX FT-NIR analyzer with adiffuse reflectance probe installed in a Perfima 200 for the coating weight monitoring, while Figure 5 illustrates an example of at-linecoating analysis with an Antaris II FT-NIR with an autosampler.

FIGURE 3. Tablet Transmission Spectral Analysis

ASARMSEC: 1.75 Corr. Coeff.: 0.9885RMSEP: 2.16 Corr. Coeff.: 0.99357 factors used

CalibrationValidationCorrectionCross-correctionIgnore

58 102Actual

5810

2C

alcu

late

d

Coating Time (hour)

Coa

ting

Dos

age

(%)

100

80

60

40

20

1 2 3 4 5 6 7

T T

FIGURE 5. At-line Coating Process Monitoring with an Antaris II FT-NIR Analyzer and An Autosampler

APIRMSEC: 2.82 Corr. Coeff.: 0.9938RMSEP: 3.845 factors used

CalibrationValidationCorrectionCross-correctionIgnore

42 146Actual

4214

6C

alcu

late

d

Result and DiscussionTransmission and reflectance measurements were attempted for the same set of tablets, and both measurements showed a verystrong correlation with the API. Since the reflectance signal from a tablet is mostly from the tablet surface, the scanned sample is only aportion of the entire tablet. Unless a tablet is uncoated and very uniform, the standard deviation of tablet reflectance measurement isusually larger than the traditional HPLC method.

The NIR beam illuminates almost the entire tablet during the transmission measurement, and the equivalent path length is much longerthan the tablet thickness. The accuracy of the tablet transmission measurement is typically compatible with the HPLC technique but inmuch fast speed. However, this transmission technique is limited by the tablet thickness.

FIGURE 4. In-line Coating Process Monitoring with Antaris MX FT-NIR Analyzer and A Diffuse Reflectance Probe

0.40

0.45

0.50

0.55

0.60

0.65

0.70

0.75

0.80

0.85

0.90

0.95

1.00

1.05

1.10

1.15

1.20

1.25

Abs

5000 6000 7000 8000 9000 10000 cm-1

Before coating

Opadry 7185cm-1

0.40

0.45

0.50

0.55

0.60

0.65

0.70

0.75

0.80

0.85

0.90

0.95

1.00

1.05

1.10

1.15

1.20

1.25

Abs

5000 6000 7000 8000 9000 10000 cm-1

After coating

4 Tablet CU Analysis and Spray-Coating Process Monitoring by Antaris FT-NIR Analyzer

Tablet CU Analysis and Spray-Coating Process Monitoring

by Antaris FT-NIR Analyzer Herman He, Ph.D.

Thermo Fisher Scientific, Lanham, Maryland, USA

Overview Tablets and capsules are the most common form of commercially available pharmaceutical products. Fourier transformed near-infrared (FT-NIR) analysis is a powerful technique to measure these materials. The advantages of using both diffuse reflectancemeasurement and transmission measurement on the Thermo Scientific Antaris™ FT-NIR analyzer will be discussed in thispresentation. This presentation also shows an example of PAT application to monitor tablet spray coating process. Because of thefast measurement speed of the FT-NIR analyzer, process operators now have the ability to estimate the coating time, and they areable to fine-tune process parameters in order to optimize the coating process to achieve better consistency in product quality.

IntroductionAPI dosage analysis and content uniformity analysis of pharmaceutical solid dosage forms is normally done by HPLC, which requirestedious sample preparation and recycling of hazardous solvents. Pharmaceutical companies are interested in easier techniques thatwould increase the number of samples per batch to allow representative trending studies and to improve quality control of tabletproduction. For these reasons, FT-NIR analysis is an appealing alternative because of its faster analysis speed. Although most tabletanalysis is conducted using diffuse reflectance, increased concerns about content uniformity have led to the desire to examine othernondestructive methods like transmission that can sample a more representative bulk volume of the tablet. Since the NIR beam canilluminate the whole tablet and travel a much longer distance, this transmission technique allows us to detect the API inside the coreof tablets and provide more representative data.

Experimental Setup Diffuse reflectance and transmission spectra were acquired on the Thermo Scientific Antaris FT-NIR Method Development SamplingSystem (Figure 1). Tablets were analyzed using the tablet detector and integrating sphere modules to allow both transmission andreflection sampling without moving the samples. Reflectance sampling parameters were 64 scans per tablet at 8 cm-1 resolution from4000 to 10000 cm-1 for the reflectance and . 6000 to 12000 cm-1 for the transmission measurement . The Standard Tablet detectorswere used for the transmission study. The diffuse reflectance spectra were measured with the integrating sphere using the internalgold flag as the background.

Summary

The spectroscopy techniques used in laboratories to obtain deep scientific and engineering understandings of products and processesare now available to the pharmaceutical industry and encouraged by the PAT initiative. This poster has illustrated how a single analyticaltechnique, FT-NIR, can be used to gain insights in a particular product or process and to gain a degree of control over a process bysimply measuring the API or CUI of tablets and making a set of process decisions for the tablet coating processes. Even though manyother spectroscopic techniques, such as Raman and UV-Vis, are available to scientists and engineers for to analyze different propertiesof products, the robustness of instrumentation, speed of analysis, and ease of use makes FT-NIR the top choice within the PAT initiativeto create scientific and engineering knowledge, a fact well established in the research community and growing in acceptance within thepharmaceutical industry.

Spectral Data Processing and PLS modeling

Both reflectance spectral and transmittance spectral data were processed first with Norris second derivative to remove spectralbaseline shift due to the light scattering from tablet samples, then with SNV (standard normal variant) in order to reduce the variation inpenetration distance or path length. The number of PLS model factors were decided by the leave-one-out cross validation method.

FIGURE 1. Antaris II MDS FT-NIR Analyzer

Transmission

Diffuse Reflection

FIGURE 2. Tablet Reflectance Spectral Analysis

CaffeineRMSEC: 0.781 Corr. Coeff.: 0.9713RMSEP: 0.830 Corr. Coeff.: 0.94963 factors used

CalibrationValidationCorrectionCross-correctionIgnore

-0 15Actual

-015

Calcu

late

d

PAT Application: at-line spay coating analysis

Many tablets today are coated after being pressed. Modern tablet coatings are polymer and polysaccharide based, with plasticizer andpigments included as well. Coatings are necessary for tablets that have an unpleasant taste and some coating formulations evencontain API that help to achieve certain functions of drug delivery. Tablet coatings are also useful to extend the shelf-life of componentsthat are sensitive to moisture or oxidation. Since spray coating is a very time sensitive process, a fast in-line or at-line measurement isneeded to control product quality and to avoid over-coating. Figure 4 shows an application of an Antaris MX FT-NIR analyzer with adiffuse reflectance probe installed in a Perfima 200 for the coating weight monitoring, while Figure 5 illustrates an example of at-linecoating analysis with an Antaris II FT-NIR with an autosampler.

FIGURE 3. Tablet Transmission Spectral Analysis

ASARMSEC: 1.75 Corr. Coeff.: 0.9885RMSEP: 2.16 Corr. Coeff.: 0.99357 factors used

CalibrationValidationCorrectionCross-correctionIgnore

58 102Actual

5810

2C

alcu

late

d

Coating Time (hour)

Coa

ting

Dos

age

(%)

100

80

60

40

20

1 2 3 4 5 6 7

T T

FIGURE 5. At-line Coating Process Monitoring with an Antaris II FT-NIR Analyzer and An Autosampler

APIRMSEC: 2.82 Corr. Coeff.: 0.9938RMSEP: 3.845 factors used

CalibrationValidationCorrectionCross-correctionIgnore

42 146Actual

4214

6C

alcu

late

d

Result and DiscussionTransmission and reflectance measurements were attempted for the same set of tablets, and both measurements showed a verystrong correlation with the API. Since the reflectance signal from a tablet is mostly from the tablet surface, the scanned sample is only aportion of the entire tablet. Unless a tablet is uncoated and very uniform, the standard deviation of tablet reflectance measurement isusually larger than the traditional HPLC method.

The NIR beam illuminates almost the entire tablet during the transmission measurement, and the equivalent path length is much longerthan the tablet thickness. The accuracy of the tablet transmission measurement is typically compatible with the HPLC technique but inmuch fast speed. However, this transmission technique is limited by the tablet thickness.

FIGURE 4. In-line Coating Process Monitoring with Antaris MX FT-NIR Analyzer and A Diffuse Reflectance Probe

0.40

0.45

0.50

0.55

0.60

0.65

0.70

0.75

0.80

0.85

0.90

0.95

1.00

1.05

1.10

1.15

1.20

1.25

Abs

5000 6000 7000 8000 9000 10000 cm-1

Before coating

Opadry 7185cm-1

0.40

0.45

0.50

0.55

0.60

0.65

0.70

0.75

0.80

0.85

0.90

0.95

1.00

1.05

1.10

1.15

1.20

1.25Ab

s

5000 6000 7000 8000 9000 10000 cm-1

After coating

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EAS2013_He_E_11/13S

Tablet CU Analysis and Spray-Coating Process Monitoring

by Antaris FT-NIR Analyzer Herman He, Ph.D.

Thermo Fisher Scientific, Lanham, Maryland, USA

Overview Tablets and capsules are the most common form of commercially available pharmaceutical products. Fourier transformed near-infrared (FT-NIR) analysis is a powerful technique to measure these materials. The advantages of using both diffuse reflectancemeasurement and transmission measurement on the Thermo Scientific Antaris™ FT-NIR analyzer will be discussed in thispresentation. This presentation also shows an example of PAT application to monitor tablet spray coating process. Because of thefast measurement speed of the FT-NIR analyzer, process operators now have the ability to estimate the coating time, and they areable to fine-tune process parameters in order to optimize the coating process to achieve better consistency in product quality.

IntroductionAPI dosage analysis and content uniformity analysis of pharmaceutical solid dosage forms is normally done by HPLC, which requirestedious sample preparation and recycling of hazardous solvents. Pharmaceutical companies are interested in easier techniques thatwould increase the number of samples per batch to allow representative trending studies and to improve quality control of tabletproduction. For these reasons, FT-NIR analysis is an appealing alternative because of its faster analysis speed. Although most tabletanalysis is conducted using diffuse reflectance, increased concerns about content uniformity have led to the desire to examine othernondestructive methods like transmission that can sample a more representative bulk volume of the tablet. Since the NIR beam canilluminate the whole tablet and travel a much longer distance, this transmission technique allows us to detect the API inside the coreof tablets and provide more representative data.

Experimental Setup Diffuse reflectance and transmission spectra were acquired on the Thermo Scientific Antaris FT-NIR Method Development SamplingSystem (Figure 1). Tablets were analyzed using the tablet detector and integrating sphere modules to allow both transmission andreflection sampling without moving the samples. Reflectance sampling parameters were 64 scans per tablet at 8 cm-1 resolution from4000 to 10000 cm-1 for the reflectance and . 6000 to 12000 cm-1 for the transmission measurement . The Standard Tablet detectorswere used for the transmission study. The diffuse reflectance spectra were measured with the integrating sphere using the internalgold flag as the background.

Summary

The spectroscopy techniques used in laboratories to obtain deep scientific and engineering understandings of products and processesare now available to the pharmaceutical industry and encouraged by the PAT initiative. This poster has illustrated how a single analyticaltechnique, FT-NIR, can be used to gain insights in a particular product or process and to gain a degree of control over a process bysimply measuring the API or CUI of tablets and making a set of process decisions for the tablet coating processes. Even though manyother spectroscopic techniques, such as Raman and UV-Vis, are available to scientists and engineers for to analyze different propertiesof products, the robustness of instrumentation, speed of analysis, and ease of use makes FT-NIR the top choice within the PAT initiativeto create scientific and engineering knowledge, a fact well established in the research community and growing in acceptance within thepharmaceutical industry.

Spectral Data Processing and PLS modeling

Both reflectance spectral and transmittance spectral data were processed first with Norris second derivative to remove spectralbaseline shift due to the light scattering from tablet samples, then with SNV (standard normal variant) in order to reduce the variation inpenetration distance or path length. The number of PLS model factors were decided by the leave-one-out cross validation method.

FIGURE 1. Antaris II MDS FT-NIR Analyzer

Transmission

Diffuse Reflection

FIGURE 2. Tablet Reflectance Spectral Analysis

CaffeineRMSEC: 0.781 Corr. Coeff.: 0.9713RMSEP: 0.830 Corr. Coeff.: 0.94963 factors used

CalibrationValidationCorrectionCross-correctionIgnore

-0 15Actual

-015

Calcu

late

d

PAT Application: at-line spay coating analysis

Many tablets today are coated after being pressed. Modern tablet coatings are polymer and polysaccharide based, with plasticizer andpigments included as well. Coatings are necessary for tablets that have an unpleasant taste and some coating formulations evencontain API that help to achieve certain functions of drug delivery. Tablet coatings are also useful to extend the shelf-life of componentsthat are sensitive to moisture or oxidation. Since spray coating is a very time sensitive process, a fast in-line or at-line measurement isneeded to control product quality and to avoid over-coating. Figure 4 shows an application of an Antaris MX FT-NIR analyzer with adiffuse reflectance probe installed in a Perfima 200 for the coating weight monitoring, while Figure 5 illustrates an example of at-linecoating analysis with an Antaris II FT-NIR with an autosampler.

FIGURE 3. Tablet Transmission Spectral Analysis

ASARMSEC: 1.75 Corr. Coeff.: 0.9885RMSEP: 2.16 Corr. Coeff.: 0.99357 factors used

CalibrationValidationCorrectionCross-correctionIgnore

58 102Actual

5810

2C

alcu

late

d

Coating Time (hour)

Coa

ting

Dos

age

(%)

100

80

60

40

20

1 2 3 4 5 6 7

T T

FIGURE 5. At-line Coating Process Monitoring with an Antaris II FT-NIR Analyzer and An Autosampler

APIRMSEC: 2.82 Corr. Coeff.: 0.9938RMSEP: 3.845 factors used

CalibrationValidationCorrectionCross-correctionIgnore

42 146Actual

4214

6C

alcu

late

d

Result and DiscussionTransmission and reflectance measurements were attempted for the same set of tablets, and both measurements showed a verystrong correlation with the API. Since the reflectance signal from a tablet is mostly from the tablet surface, the scanned sample is only aportion of the entire tablet. Unless a tablet is uncoated and very uniform, the standard deviation of tablet reflectance measurement isusually larger than the traditional HPLC method.

The NIR beam illuminates almost the entire tablet during the transmission measurement, and the equivalent path length is much longerthan the tablet thickness. The accuracy of the tablet transmission measurement is typically compatible with the HPLC technique but inmuch fast speed. However, this transmission technique is limited by the tablet thickness.

FIGURE 4. In-line Coating Process Monitoring with Antaris MX FT-NIR Analyzer and A Diffuse Reflectance Probe

0.40

0.45

0.50

0.55

0.60

0.65

0.70

0.75

0.80

0.85

0.90

0.95

1.00

1.05

1.10

1.15

1.20

1.25

Abs

5000 6000 7000 8000 9000 10000 cm-1

Before coating

Opadry 7185cm-1

0.40

0.45

0.50

0.55

0.60

0.65

0.70

0.75

0.80

0.85

0.90

0.95

1.00

1.05

1.10

1.15

1.20

1.25

Abs

5000 6000 7000 8000 9000 10000 cm-1

After coating