SPECTROSCOPIC IMAGING OF COMPACTED PHARMACEUTICAL TABLETS

K. L. Andrew Chan, Noha Elkhider, Sergei G. Kazarian,

Department of Chemical Engineering

MotivationGreat interest is often focused on the distribution of differentcomponents in the tablet as this would affect the integrity of the tablet and ultimately the bioavailability and effectiveness of the

pharmaceutical product. This poster presented the application of attenuated total

reflection infrared spectroscopic imaging method to study tablet compaction in situ, including:

• Revealing the distribution of different components[2] in a tablet

• Quantitative analysis of the imaging data with univariate(single band integration) and multivariate approaches (classical least square).

• Studying the effect of additives and humidity to the compaction properties such as the density distribution at the

surface of the tablet

Diamond ATR Crystal

Tablet

Punch

Gate

Screw hole

Torque

Infrared beam

•Focal plane array detector in combination with a diamond ATR accessory[3] for FTIR images acquisition.•Tablets are compacted directly on the diamond and measurements are followed without removing the tablets.•Custom made compaction cell for in situ compaction and FTIR imaging measurement•Compaction pressure used = 120 MPa

Approach

Classical Least Square (CLS) data treatment

A spectral data cube D containing 1000 data points for each spectrum, 4096 spectra and 3 components in the system, the size of the matrix D, T and C will be 4096 x 1000, 3 x 1000 and 4096 x 3 respectively. T represents the pure components matrix and C represents the “concentration” matrix.

D

4096

10

00 = C

4096

3T

3

x

Compaction study of avicel with different concentration of paracetamol

Wavenumber/cm-1

RGB image shown the result from the CLS

analysis of the tablet made of three components

with similar spectral features

Comparison of reconstructed spectra (grey line) with original spectra (dark line)

Avicel rich

HPMC rich

Lactose rich

Band integration

Av

icel

Caff

ein

e

Band integration Band integrationCLS CLS CLS

90% Avicel 10% Caffeine 50% Avicel 50% Caffeine 10% Avicel 90% Caffeine

100

µm

100% HPMC

95% HPMC 5%

Magnesium stearate

60% RH 80% RH

Diamond

Tablet

CLS/Band integration

FPA

Effect of humidity to HPMC compaction

Effect of additive to HPMC compaction

• Distribution of different components in a compacted tablet has been studied in situ without the need of staining or chemical

marking of components. • With the aid of the new compaction cell, the compaction force can be controlled and measured which lead to the possibility of

studying the effect of compaction force on distribution of different components in a tablet. • Close agreement between the results obtained from both multi- and univariate analysis demonstrated the reliability of the multivariate approach.

• The power of multivariate approach was demonstrated to distinguish different components when the absorption bands overlap. This approach is extremely useful for the analysis of formulations containing many ingredients.

• The addition of 5 wt% MgS increases the density of the tablet by lubricating the HPMC particles causing an increase in absorbance which was detected via FTIR imaging. This quantitative information is important for design of tablets with high resistance to shock and abrasion and for optimisation of tablet production in pharmaceutical powder compaction technology.

Conclusions

Wavenumber

Wavenumber

Comparison of reconstructed spectra

(grey line) with original spectra (dark line)

Absorb

anc

eA

bsorb

anc

e

Reference:[1] K. L. A. Chan, N. Elkhider, S. G. Kazarian, Chemical Engineering Research and Design,83 (2005), 1303-1310 .

[2] K. L. A. Chan, S. V. Hammond, S. G. Kazarian, Analytical Chemistry 75, (2003), 2140-2146 [3] K. L. A. Chan, S. G. Kazarian, Applied Spectroscopy 57, (2003), 381-389

Acknowledgements: Dr. Jaap van der Weerd, Richard, EPSRC, Bruker Optics, Specac