The formulation and evaluation of alcohol-free paediatric paracetamol preparations

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amounts of p-aminophenol (figure 2) as a by-product of dye manufacture (Hardman & Limbird, 1996:631; Knoerzer, 2002:5; Nancy West Communications, 2004:4-5).

OH

Fiqure 1: Carl Duisberg Figure 2: Para-aminoDhenol (Bayer 2004: 1) r I I I I NHCOCH3 I_I I I I I

-

II

\ I _

NHCOCH3

ANILINE CONJUGATED PARACETAMOL PARA-PHENETIDIN

j

R = glucuronate (major)

R = sulphate (minor)

j

METHEMOGLOBIN-FORMING AND OTHER TOXIC tv'ETABOLITES

Scheme 1: Para-aminoDhenol derivatives and their interrelations (Hardman & Limbird, 1996:631)

Page 2 of 120

---OH I

OC2H5 ACETANILIDE I PARACETArv'OL I PHENACETIN

I I

j

-t---;

j

NH2 NHCOCH3 NH2

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.

T1/2> 12 hours: Hepatic coma is likely

(Hardman & Limbird, 1996:632; Katzung, 2001 :615).

c o 1G .... ... c G) (.) c o U

as:=:-E"a

tn

E

.!!-0.. o E as ... G) (.) as .... as 0..

400

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100

50 o

Severe hepatotoxicity likely

o

5

10

15

20

25 Hours after ingestion

Chart 1: Paracetamol Dlasmaconcentration as measure of (Sommers, 1997:38)

HS

Figure 4: Acetvlcysteine (Lund, 1994:710)

In all cases where significant poisoning is suspected, treatment should not be delayed while awaiting laboratory results. Gastric lavage should preferably be performed within 4 hours of ingestion. N-acetylcysteine (figure 4) is a useful antidote

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Fiaure 3 : A suspension subiected to 40°C I 75% RH

\.1 n)", 10 20

30

40

50

Fiaure 4 : Paracetamol crvstals

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