Pharmaceutical colourants
Overwiev of approved and used pharmaceutical colourants
A possible classification:
1. Inorganic pigments
2. Organic dyes
2.1 Lipophilic dyes
2.1.1 Carotenoids
2.1.2 Xanthophyls
2.2 Hydrophilic dyes
2.2.1 Fused-rings glycosides, pseudoglycosides and their aglycones
2.2.2 Phenolic dyes not based on fused rings
2.2.3 Indole dyes
2.2.4 Hydrophilic azo-dyes
2.2.5 Hydrophilic triarylmethane dyes
1 .Inorganic pigments •in most insoluble or poorly soluble in both water and organic solvents •colouring of tablet mass, capsules, surface films on coated tablets •colouring of suspension creams and oitments
CaCO„ E 170
3'
•only for surface „colouring"
Ti02, E 171, CI 77891, titane white
•also protecting factor against UV irradiation
Iron oxides and hydroxides E 172 Ferric-ammonium citrate
3+
Fe NH
•Steinsvik S. et al.: J. Phys. Chem. Solids 58, 969 (1997)
•water soluble
•since 2002 rejected as a colourant; before 2002 approved in USA; still listed in DAC (=Deutsches Arzneimittel Codex = German Medicines Codex)
1. Inorganic pigments
Al E 173, CI 77000
•finely powdered - inflammable (pyrophoric)
2.1. Lipophilic organic dyes Carotenoids (together E 160) a, p, y-carotene together E 160a
CH
CH
CH
CH3
oc-carotene (p,e-carotene) m.p. 187,5°C •logP =17.49
° o/w
CH,
CH3	
A,	
	^CH3
	CH3
CH
CH3
p-carotene
CI 75130 (natural), CI 40800 (syntethtic) E 160a m.p. 183°C
•poorly stable on air and light •from light yellow to deep orange in dependence on concentration •0.1% for suppositories •logP =17.63
° o/w
y-carotene (p,6-carotene) m.p. 154°C •logP =17.63
° o/w
Carotenoids (together E 160) - continued
capsanthine, E 160b •from bell peppers
HO
Q H,C
H3C  CH3 Ö
CH„
CH,
OH
CH,
capsorubine, E 160c •from bell peppers
(capsanthine + capsorubine = bell peppers extract, Paprika ole<jr_psin)
lycopene, E 160d, CI 75125 • from tomatoe •yellow •m.p. 175°C •logP =17.64
° o/w
Xanthophyls •together E 161
H3C
CH.
CH.
CH
HO
CH
HsCv^^OH
CH,      H3C CH3
luteine, E 161b •colourant of the egg yolk •m.p. 196°C .log P =14.82
° o/w
CH      H3C CH3
canthaxanthine, CI 40850, E 161 g
•orange
•log P , =14.1
° o/w
•antioxidant, believed to be a cancer protectant
2.1 Hydrophilic organic dyes 2.1.1 Fused-rings glycosides, pseudoglycosides and their aglycones
Anthocyanidines = hydroxylated and methoxylated derivatives of 2-phenylbenzopyrylium •together E 163 •aglycones of anthocyanins
Name	R1	R2	origin	m.p. [°C]	log P 3 o/w	colour	I [nm] max L J
pelargonidine H		H	Pelargonium	> 350	2.68	salmon	529
kyanidin	OH	H	Cyanus	> 300	2.2	red	544
delphinidine	OH	OH	Delfinium	> 350	2.14	blue	553
peonidine	OCH3	H	Peaeonia			red	543
petunidine	OCH	OH	Petunia			blue-red	522
malvidine	OCH	OCH 3	Malva	> 300; 202-203	2.33	pink-red	553
•in plants as glycosides in most in position 3, particularly esterified with subst. cinnamic acids or acetic acid in pos. 6
•the colour of free aglycons depends on pH: blue in alkaline, red in acidic, this is not valid for glycosides
•increasing number of hydroxyles results in a more intense colour, methylation of hydroxyles shifts the shade from blue to red
J. Ague. Food Chem., Vol. 53, No. 6, 2C05 1961
niAi:
Figure 1. Reoresentative profile of a grape e>::ract analyzed by reversed phase HPLC af 52C nm: as described under Ma:erials and Me:hods: malvidine-3-glucoside delphinidin 3-glucoside (Delp3gl): cyanidin 3-glucoside (Cyan3gl): petunidin
3-glucoside <Pel3gl), peonidin 3-glucoside (Peon3gl), malvidin 3-glucoside (Mslv3gl), and their corresponding acetic acid (ac) and p-counaric acid es:ers (p-coum).
Riboflavine (vitamin B2, lactoflavine) E 101 •yellow
•listed in PhEur, CzP2009, BP, USP, JP •Relative absorbance A      /A =0.31
373 nm        267 nm
0.33, A       /A9R7 =0.36
444 nm        267 nm
O OH
Carmine (= carminic acid, coccinellin, cochineal extract, CI 75470, E 120) •deeply red •fruit odour
•water solubility cca 30 g /1
•X    (buffer pH = 3) = 490 - 493 nm
2.2.2 Phenolic dyes not based on fused rings
HO
O
Curcumin E 100
•yellow-orange •approved in EU
•from turmeric root (Curcuma longa)
2.2.3 Indole dyes
indigo carmine
indigotindisulfonate sodium [USP] E 132, CI 73015, FD&C blue #2
•deeply blue powder, aqueous solutions are blue or blue-purple •X   = 604 nm
max
2.2.4 Hydrophilic azo-dyes
0=S
O
O
tartrazine, CI 19140, E 102,
acidic yellow 23, egg yellow A
•orange-yellow
.log P t  „ t =-10.17
^ octanol/water
Na
0
1
s=o o
Na
carmoisine, azorubin, E 122,CI 14720, C.I. Acid Red 14, chromotrop FB •LD (p.o., mouse) = 8 g / kg
2.2.5 Hydrophilic triarylmethane dyes
HX
Brilliant Green, CI 42040, Viride nitens, Malachite Green G, Emerald Green •not approved as drug and food dye, but listed in many pharmacopoeias as a therapeutic (antiseptic) •m.p. 210°C .log P =2.01
° o/w
.LD50 = 3 - 8 mg / kg
CH, CH
•Acid Green 50, Green S, CI 44090, E 142, Brilliant Acid Green BS, Food Green S •LD =2g/kg
o=s-o Na+
o
Fast green FCF, CI 42053, Solid Green FCF, Food Green 3
•X   (ethanol 50 %) 622 - 626 nm
maxv '
•spec, absorbance A 1%    (X   ; 0.003 g/l; ethanol
r 1cm v   max ° '
50%) = 1360-1610 •log P o/w = -5.42
Na
Na
Erythrosine (erythrosine B, CI 45430, E 127)
reddish-brown X    (water) =     524 - 527
max
Phloxine B (CI45410, D&C red #28,
Eosine Blue)
deeply brown
X    (ethanol 50%) = 546 - 560 nm
max
A1%   (X   ; 0.005 g/l; water) = 930 - 1170
1cmv max' °  ' 7
LD5Q(p.o., rat) = 1.84 g / kg
nm
specific absorbance
A 1%   (k   ; 0.005 g/l; ethanol 50%) = 930
1cmv max' °  ' 7
1400
LD5Q(p.o., rat) = 8.4 g/kg