Infrared sp ectrophotometry

Infrared

sp

ectrophotometry

David

G.

Watson

Lecture

5

EMAD.ALSAMARRAI

/-HftEt

Atpd*f$

'*

stearate and croscarmellose sodium.s The most notable variations

in

absorbance

intensity

in

the spectrum

of

the blend

occur

at2030 nm and 2240 nm. Absorbance at these wavelengths can be attributed to hydrochlorothiazide and lactose, respectively' The more complete the blend, the less the standard deviations

of

the absorbances at these wavelengths obtained when several batches sampled at the sarRe time

point

are compared.

As would

be expected, the standard deviations shown

in

Figure 5'17 decrease

with

blend time, but the decrease is less marked after

l0

min.

In

this study

it

was found that blending

for

more than 20

min

caused a loss

in uniformity

due

to

an alteration

in

the

flow

pioperties

of

the powder, resulting

from

a change

in

the

distribution

of

the magnesium stearate.

NIR

probes can be inserted

directly

into blenders

to monitor mixing.

Determination

of

active

ingredients

in

multicomponent

dosage

forms

NIRA

has been used

to

analyse multicomponent tablets, e.g. aspirinlcaffeinel

butalbarbital, and can examine such tablets

in

a passffail manner.u The tablets

fail

when the ingredients

fall

outside the specified range as shown in Figure 5'19, which is derived by the monitoring of two wavelengths in the

NIR

spectrum of the

formulation'

This might

appear simple but a great deal

of

development

work

was carried out in order to determine which wavelengths to monitor in order give the best discrimination'

In-pack

determination

of

active

ingredifnts

In

clinical trials

of

a new drug

it

is important to ensure that the tablets have been packed and coded correctly. Figure 5.20 shows the absorbance of tablets monitored at a wavelength

which

can be correlated

with

the content

of

active ingredient.T

It

was possible to distinguish between tablets containing 0,

5,

10'

15 and 207o

of

the active ingredient.

tt

was also possible

to

adapt the method

to

determination

of

the active ingredient

of

the tablets

'in

pack' using a

fibreoptic

probe, although the precision was

not quite as good as that obtained

from

the unpackaged tablets'

Determination

of

Polymorphs

NIRA

provides a non-destructive alternative

to differential

scanning calorimetry

for

the determination

of polymorphic

forms

of

drugs, e.g. the

polymorphic

forms

of

caffeine.a

NIRA

has also been used

to

determine optical

purity. While

the pure

Fig.5.19

Application of NIRA to control of the ingredients in tablets containing three comPonents. Reproduced with permission from SpectroscoPY (see Reference 6). 0.64 0.63 0.62 0.61 0.60 0.59 0.58 0.57 0.56 0.55 o.'ss o.so 0.57 0.58 0,59 0.60 0'61 0.62 in ..1*. E

s

q) N N 0) (J o o alt Absorbance al2266nm

tt" N

o

r x c o ttl i(! !> i,: lC) :-O :e 'A -0.35 -0.75 -1.15 Fig. 5.20 Determination of the amount of active ingredient in tablets bY

direct use of NIRA.

Reproduced with

permission from J. Pharm'

Biomed. Anal. (see

Reference 7)'

opposite enantiomers

of

a substance have identical

NIR

spectra'

mixing

two enantiomers together causes a change

in

the spectrum' Thus there

is

potentiaf

for

determining the percentage of each enantiomer

in

an enantiomeric mixture and hence

for

the control

of

enantiomeric impurities'a

M

oistu

re determi

nation

Moisture determination by

NIRA

continues to be an area

of

interest.

In

a recent paper the determination

of

water

in

the anti-fungal compound caspofungin acetate was

J"*onrrruted.s

The method used the chemometric method

of partial

least squares

(pLS)

analysis

of

the second derivative spectrum

in

order

to

develop a quantitative method

for

water

in

the samples. The

NIRA

method was validated against

Karl

Fischer

titration.

The water affects the whole spectral region between 950 and 1650 nm and thus a method examining the effects

of

increasing levels

of

water on the whole spectral region was found

to

be robust' The PLS method uses broad bands

of

wavelengths

to

construct a calibration model. The statistical concepts are quite

difficult

to understand; however, a recent booke provides an excellent introduction

to

chemometrics,

which

is a subject

of

increasing importance in analytical chemistry.

process

_control

of

components

in

a shampoo

NIRA

was studied as a technique for process control in the manufacture of shampoo.'o The formulation contained detergent, solids, water and

glycerol' In

order to carry out the process control, samples of shampoo were taken at various points in the production

pror.r..

NIR

reflectance spectra were obtained

for

75 samples over the range

11012500

nm.

A

multiple

step-up linear regression analysis was performed at nine wavelengths.

This

type

of

statistical test consists

of multiple

correlations

of

\ \ablets conraining 5% of experimental

drug

\uul"rt.ontalnlng 10% ol experimental drug

Tablets containing 2090 of expelilnental

1472

1474

: t: t: ir ::l::t ',! t!t::i:!i

absorbances at different wavelengths

with

the concentration

of

the ingredients

of

the shampoo determined

by

classical methods. Correlation coefficients

of

0.99 were obtained

for

water, solids and detergent,

with

a rather

lower

correlation

for

glycerol,

which at

lTo

in

the

matrix

was close

to

the

limits of

detection. The technique was deemed suitable

for flow-through monitoring.

The computer

monitoring

of

the process

by

NIRA

could be used to

control

actuators and valves

within

the chemical processing plant.

Additional

problerns

1

.

Four steroids (i), (ii), (iii) and (iv) correspond to the structures below (Fig. 5.21). The steroids

are analysed by lR as KBr discs. The principal bands in their spectra between 1500 cm-l "nA+OOti.r-t.rugiven below. Determinewhich

of thestructuresgiven belowcorrespond

to (i), (ii), (iii) and (iv).

(i)

Steroid ca 3000 cm-1, 1710 cm-1, 1670 cm-1, 1620 cm-1'

(ii)

Steroid 3450cm-1 (broad band), ca 3000cm-1, 1710cm-l, 1550cm-t, 1620cm-t'

1610 cm-r.

Steroid 290f3500 cm-1 (very broad band obscuring other bands in this region)'

1605 cm-1, 1580 cm-1, 15oo cm-1.

St"-iJ

3400 cm-l (broad band), ca 3000 cm-1, 1570 cm-l, 1505 cm-l.

Fig. 5.21

Testosterone Progesterone

HO

Oestradiol

uexametnasurre

ouoJalsolsal (^t) :lotpeJrsao (t1) :auoseqlaurexap (1;) iauolalsaEotd (t):tansuy 2. The principal bands between 1500 cm-l and 4000 cm-1 are given for the m6lecules shown

below (Fig. 5.22). Associate each set of data with one of the molecules.

[i

-."

ioijo.;:';ti;rjgoo.1n-'

(very b.road), 1600.cm-l (weak), 1500 cm 1.

(ii)

3300-3500 cm-r (broad), ca

3000.t-t,

t75O cm-1,1720cm-1, 1650 cm-1, 1612 cm-l,

1600 cm-r.

tiiil

giZg

_ir-t

_{rh.rp), 2300-3200 cm-1 (broad band obscuring other bands in this region),

' '

iiAg;;-r

iwitfr siigl",t s6outder at

i750.r-t),

1690 cm-1, 1505 cm-1, 1580 cm-r,

1500cm1.

(iv) 3380 cm-l, 3320 cm-1, ca 3000 cm -1, 2300-2900 cm 1 (very broad), 1690 cm-',

1620 cm-1, 1500 cm-1, 1500 cm-1. (iii) (iv) :tl Dexamethasone (Continued)

Additiohal:

Fig.

5.22

Ct-coocH2cHrilHlcrHu;, I

a\

ttl

I NHz Procaine.HCl

cl-? HOCH2CH2NH(CH3)2 Diphenhydramine.HCl

11p'aurero:d (nt) iut;1t:tdtue (ttt) ia1e1a:e

pJk"-7ff$1,

o'

cooH

a

6

Ampicillin Prednisolone acetate

auolos!upard (rr) l11g'aurue.rplquaqdtp (t) :raMsuv I

References

1. Williams DH, Flemingl. Spectroscopic Methods in Organic Chemistry,4th ed. London:

McGraw-Hill; 1989.

2. Schrimer RE. Modern Methods of Pharmaceutical Analysis, vol. l . Boca Raton: CRC hess; l99l '

3. Hartauer KJ, Miller ES, Guillory IK. Int J Pharm 1992;85:163:14.

4. Ciurczak EW. Applied Spectroscopy Reviews 1987;23:14743. 5. Wargo DJ, Drennen JK.,t Pharm Biomed Anal 1996;14:1415-23.

6. Ciurczak EW, Maldacker T. Spectroscopy 1986;l:3G9.

7. Dempster MA, Jones JA, Last IR, MacDonald BF, Prebble KA.,f Pharm Biomed Anol 1993;

rl(12): t087-92.

8. Dunko A, Dovletoglou A. J Pharm Bionted Anal 2002;28:145-54.

9. Brereton RE. Chemometrics. Data Analysisfor the Laboratory and Chemical Plant. Wiley; 2003.

10. Walling PL, Dabney JM.

/

Soc Cosmet Chem 1988;39:l9l-9. Further reading

Bunaciu AA, Aboul-Enein HY, Fleschin S. Application of Fourier transform infrared spectrophotometry in pharmaceutical drugs analysis. Appl Spectosc Rev 2010;45:206-19. Bunaciu AA, Aboul-Enein HY, Fleschin S. Recent applications of Fourier transform infrared

spectrophotometry in herbal medicine analysis. Apltl Specn'osc Rev 20ll;46:2514O.

Karande AD, Heng PWS, Liew CV.In-line quantification of micronized drug and excipients in tablets by near infrared (MR) spectroscopy: Real time monitoring of tabletting process. Int .I Pharm 2010;396:63-74.

Komsta L, Czarnik-Matusewicz H, Szostak R, et al. Chemometric detection of acetaminophen in pharmaceuticals by infrared spectroscopy combined with pattern recognition techniques:

Comparison of attenuated total reflectance-FTlR and Raman spectroscopy. J AOAC Int 2Oll:94:743-9.

Mantanus J, Ziemons E, Lebrun P, et al. Active content determination of non-coated pharmaceutical pellets by near infrared spectroscopy: Method development, validation and reliability evaluation. Talanta 2010;E0: I 750-7.

Sasic S. Parallel imaging of active pharmaceutical ingredients in some tablets and blends on Raman and near-infrared mapping and imaging platforms. Analytical Methods 2011;3:806-13'

Additional

reading

Socrares G. Infrared Characteristic Group Frequencies: Tahles and Charts. 2nd ed. Wiley Interscience; 1994.

Griffiths P, De Haseth JA. FourierTransfornr Infrared Spectrometry. Wiley Interscience; 1986.

Murray I, Cowe IA. Making LightWork: Advances in Near InJVared Spectroscopy. Wiley Interscience;

t992.

S iesler HW. Near- i nfi'ar e d S p e c t r o s c opy. Wi ley-VCH; 2002.

Journal of Near Infrared Spectroscopy

Usefulwebsites

www.spectroscopynow.com

Good coverage of IR, NIR spectroscopy and also chemometrics.

hup://www.ijvs.com/index.html

Website of electronic joumal on vibrational spectroscopy. Useful articles both introductory and advanced. Strong focus on Raman sPectroscopy.

http ://www.spectroscopyeurope.com/