Adsorption of Drugs onto Activated Charcoal and Its Effects on Drug
Absorption and Toxicity
A) Introduction :
Activated charcoal has been widely used in the chemistry and pharmacy
laboratories as the most effective decolorizing agent in the purification process
primarily due to its strong adsorption property . It must not be constructed, however,
that it cannot adsorb colorless chemicals.
In medicine, activated charcoal has been widely used , especially in Europe , as
an antidote for a number of drug poisoning . It is an ingredient of the so-called “
universal antidote.” It can be used orally or as a charcoal artificial kidney ( H .
Yatzidis , in Acute Barbiturate poisoning , edited by H . Matthew , Excerpta Medica
Foundation , Amsterdam ).
In the latter method, the blood is perfused through about 200 g . of activated charcoal
granules coated with cellulose acetate at a flow rate of 150 ml . per minute . It is
believed that its clinical use in this country will soon increase considerably as
physicians and pharmacists are becoming more aware of its rational and efficacy .
It is of interest to note that one of the earliest advocates for the use of activated
charcoal as an antidote was a French pharmacist, Bernard Touery. When his theories
were questioned he demonstrated his faith in them in a manner unlikely to be
followed by modern clinicians. At a meeting (around 1830) in the French Academy
he swallowed several times the lethal dose of strychine, together with 15 g of
charcoal .He remained unaffected by this heroic experiment, yet it did not impress
the medical profession.
Activated charcoal is usually prepared from destructive distillation of wood
pulp ; and it is treated to increase its adsorptive properties . The best activated
charcoal has small particle size, large total surface area, and low mineral content. The
adsorptive property is due to the interaction of p-orbital electrons ( electrons) of
carbon atom with the absorbate in the form of van der Waal force and/or induced
dipole-ionic force interactions. Therefore, in a strict sense, the charcoal adsorption is
usually classified as a physical rather than chemical phenomenon, which involves
covalent bonding.
There are many adsorbents used clinically such as Kaolin , aluminium
hydroxide , attapulgite , magnesium trisilicate and cholestyramie . Plasma and tissue
proteins including receptor sites for drug action can also function as adsorbents for
many drugs and endogenous substances . These binding properties have important
bearing upon their metabolism , distribution , excretion and biological activities , The
displacement of a drug from the binding site by another drug is one of the most
important factors causing clinical drug interactions . A pharmacist should be also
aware of the possible sorption ( adsorption and absorption ) of drugs and
preservatives onto plastic containers , tubes and filter paper ( such as Millipore filter )
.
The adsorption and binding phenomena usually follow law of mass action .
From a simple mathematic manipulation , one can estimate percent of drugs
adsorbed or bound at various concentrations of adsorbents and drugs , maximum
adsorbing or binding capacity per unit of adsorbent and the number of binding site on
each molecule especially when the adsorbents are in the solution state .
Langmuir first proposed a theoretical treatment of the adsorption phenomena.
The two assumptions based on which the Languir adsorption isoterm equation is
derived are :
One) Monomolecular adsorption
Two) Adsorption at one site does not affect adsorption at another site.
Fraction occupied =  = X/X max
Fraction unoccupied = ( 1 -  )
Rate of adsorption = K1 (1 -  ) Ceq = r1
Rate of desorption = K2 ( ) = r2
At equilibrium, r1 = r2
By arrangement:  = [(K1 / K2 ) . ( C eq )] / [ (1 + (K1 / K2 ) ) . ( C eq )]
(K1 / K2 ) = b = adsorption affinity
Substituting for  :
X/X max = [ b . ( C eq )] / [ (1 + b ) . ( C eq )] = ( X /m ) / (X max / m )
Where “m” is the amount of adsorbent.
Multiplying both sides by C eq gives:
C eq / ( X / m ) = (1 / (X max / m ) * b) + [C eq / b (X max / m )]
Where b is (X max / m ) = Y m and ( X / m ) = Y, Then
C eq / Y = [(1 / (Ym * b ] + [C eq / Y m )]
A plot of [C eq / ( X / m )] versus C eq should give a straight line with a slope of
[1/(X max / m )] and an intercept [1/ b * (X max / m ) ]
There are many factors affecting the sorption of drugs onto adsorbents . They
mat include (a) pKa of a drug , (b) competitive substances (s) , (e) temperature , (f)
molecular size and shape , ( steric effect ) of drug , (g) solubility ( hydrophobic
bonding ) of drug , (h) concentration of adsorbent and drug , (i) physico-chemical
nature of the adsorbent .
It has been reported ( A.H. Andersen , Acta . Pharm. Tox . , 2 , 69 ( 1946 ))
that 1 g of activated charcoal could adsorb the following amount of chemicals in
water :
Chemicals
Mercuric chloride
Sulfanilamide
Strychnine nitrate
Morphine hydrochloride
Atropine sulfate
Nicotine
Barbital
Barbital sodium
Phenobarbital sodium
Aprobarbital sodium
Allobarbital sodium
Hexobarbital sodium
Cyclobarbital calcium
Salicylic acid
Phenol
Alcohol
Potassium cyanide
Molecular Weights
Maximal Adsorption(mg)
271.5
172.2
397.4
375.8
694.8
162.2
184.2
206.2
254.2
232.2
208.2
258.3
236.3
(for cyclobarbital )
138.1
94.1
46.1
65.1
1,800
1,000
950
800
700
700
700
150
300 – 350
300 – 350
300 – 350
300 – 350
300 – 350
550
400
300
35
It has also been reported that one gram of activated charcoal absorb 250 mg of
imipramine ( M.W. 284.4 ) , an antidepressant .
Tsuchiya and Levy ( J. Pharm .Sci. , 6, 586 , (1972)) reported the adsorption
capacity of activated charcoal at various pH’s and its effect on absorption in humans
for three types of drugs ( weak acid , weak base and a compound largely unionized in
GI tract ).
TABLE I : Adsorption capacity of activated charcoal at various pH’s in term of
milligrams ( millimoles ) per gram at 37o C .
Drug ( pKa )
Aspirin ( 3.5 )
Salicylamide ( 8.2 )
Phenylpropanolamine (9.0)
pH
1.0
283 (1.57)
370 (2.70)
95 (0.63)
8.2
10
12
133 (0.74)
367 (2.68) 250 (1.82)
128 (0.85)
303 (2.0)
TABLE II : Effect of activated charcoal on absorption in humans .The drugs were
given in solution together with activated charcoal on an empty stomach . The data
were obtained from the average of four subjects studied.
Aspirin (1g )
Salicylamide
(1g )
Phenylpropanolamine (50 mg)
Activated charcoal given , g
% of dose recovered in urine
Activated charcoal given , g
% of dose recovered in urine
Activated charcoal given , g
% of dose recovered in urine
0
99.7
0
92.5
0
80
1.9*
87.4
1.5*
71.8
0.5*
42
10
60.6
10
21.4
5
6.5
These doses which could adsorb 50 % of the drugs were calculated from
adsorption isotherms.
B ) Objectives :
The following objectives are hoped to accomplished after the completion of the
experiment:
1.
Understanding of basic principles and factors affecting sorption and binding
phenomenon.
2.
To be able to apply the Langmuir adsorption isotherm equation to predict
fraction of drug adsorbed and maximum adsorbing capacity of adsorbent.
3.
To understand and predict the clinical implications and applications of sorption
and binding phenomenon.
4.
To show students the efficacy of activated charcoal as an antidote for
strychnine sulfate.
Adsorption process can be presented by :
A solute + S ( K1 / K2 ) AS
Where
A solute = Concentration of the adsorbent present in the medium .
S
= Vacant sites on adsorbent
AS
= Occupied sites
Freundlich equation can be linearized by taking the logarithmic from ( Eq. 3 ) of
Eq.1 . However Langmuir equation can be linearized by taking the reciprocal of the
equation as shown in equation 4 & 5 :
Log ( X / m ) = ( 1/ n ) Log C + log K ------------------------------------ ( 3 )
1/Y
= 1 / Ym + ( 1/ Ym .b ) ( 1/ Ce ) --------------------------- ( 4 )
Ce / Y
= 1/ Ym .b + ( Ce / Y ) ------------------------------------ ( 5 )
In this experiment oxalic acid will be used as the adsorbate and charcoal will
be used as adsorbent .
Experimental
1.
2.
3.
4.
5.
6.
Procedure :
In each of 6 Erlenmeyer flasks introduce 5 g of the adsorbent ( charcoal ).
To each of them add 50 ml of a known dilution of a standard solution of oxalic
acid provided ( e.g. 1N , 0.8N , 0.4N and 0.1N ) according to Table III .
Shake occasionally for 15 minutes and set a side for half hour to achieve
equilibrium .
Filter , reject the first portion of the filtrate after washing the receiver with it .
Titrate , 25 ml of the aliquot filtrate in each case with 0.5N sodium hydroxide
using phenolphthalein as an indicator ( 2 drops)
Calculate the amount adsorbed in each case and list your result in Table IV.
Data Analysis :
1.
Each group of students should cooperate to run the experiment.
2.
From Table IV , plot X/m vs. Ce , Log X/m vs. Log Ce and Ce / (X/m) vs. Ce
.
3.
Analyze each graph and write your report .
TABLE III
Flask
1
2
3
4
5
6
1 ml of 1N oxalic
50
40
30
20
10
5
Distilled water
0
10
20
30
40
45
Normality of oxalic
1N
0.8N
0.6N
0.4N
0.2N
0.1N
TABLE IV
Oxalic
acid
conc.
ml
from
1N
oxalic
mls of
H2O
to 50
Initial
conc.
g/50 ml
cl
End
point
mls of
0.5N
NaOH
Equilibrium conc.
(Ce )=
[E.P(0.0225)/vol.] 50
Amount
adsorbed
Log
Ce
Log
(X/m)
X/ m
1N
0.8N
0.6N
0.4N
0.2N
0.1N
* 1 ml of N/2 NaOH = 0.0225 g oxalic acid .
x= [ initial conc. (g/50 ml ) – Equilibrium conc. (g/50 ml) ]
m= 5 g .