THE ADSORPTION OF SELECTED ANTIBIOTICS BY KAOLIN by PENPAN ASWAKUN B. PHARM ...

132 Pages·2009·4.85 MB·English

THE ADSORPTION OF SELECTED
ANTIBIOTICS BY KAOLIN
by
PENPAN ASWAKUN
B. PHARM., MAHIDOL UNIVERSITY
BANGKOK, THAILAND, 1968
A THESIS SUBMITTED IN PARTIAL FULFILMENT OF
THE REQUIREMENTS FOR THE DEGREE OF
MASTER OF SCIENCE
in the Division of Pharmaceutical Chemistry
of the Faculty of Pharmaceutical Sciences
We accept this thesis as conforming to the
required standard
THE UNIVERSITY OF BRITISH COLUMBIA
OCTOBER, 1975
In presenting this thesis in partial fulfilment of the requirements for
an advanced degree at the University of British Columbia, I agree that
the Library shall make it freely available for reference and study.
I further agree that permission for extensive copying of this thesis
for scholarly purposes may be granted by the Head of my Department or
by his representatives. It is understood that copying or publication
of this thesis for financial gain shall not be allowed without my
written permission.
Department of
The University of British Columbia
2075 Wesbrook Place
Vancouver, Canada
V6T 1WS
t4 @&foL>r /f7r
Date
ABSTRACT
In this investigation, the in vitro adsorption of
tetracycline hydrochloride, neomycin sulfate, lincomycin
hydrochloride, chloramphenicol, and ampicillin trihydrate by
kaolin were studied. Adsorption studies were carried out at
37.0°C. in water and in pH 1.2, 3.0, and 5.0 solutions.
The adsorption isotherms for tetracycline hydrochloride,
neomycin sulfate, and lincomycin hydrochloride in aqueous
solution were of the Langmuir type, with the following exceptions.
(a) A Ereundlich adsorption isotherm was obtained for
tetracycline hydrochloride in pH 1.2 solutions.
(b) An S type adsorption isotherm, (according to the
classification of isotherms by Giles and his co
workers (1960) was obtained for lincomycin
hydrochloride in pH 1.2 solutions.
In general, adsorption varied with the pH of the solutions.
Chloramphenicol and ampicillin trihydrate are not adsorbed by
kaolin.
Desorption studied for the adsorbed antibiotics were
carried out in. water. The results indicated that the adsorption
of tetracycline hydrochloride by kaolin is a reversible
process, the adsorption of neomycin sulfate by kaolin is an
irreversible process, and the adsorption of lincomycin
hydrochloride is a partially reversible process.
On the basis of data obtained, it was found that 47.21%
of 250 mg. tetracycline hydrochloride dose and, 57.98% neomycin
base (220.5 mg.) would be adsorbed by six gm. of kaolin.
On the basis of a 500 mg. dose of 1incornycin hydrochloride/
11.44% would be.expected to be adsorbed by.six gm. of kaolin.
This value increases to 33.94% if 17.76 gm. of kaolin are'
administered to the patient.
If the above two values are compared to the in vivo data
reported by Wagner (1966), it becomes evident that the decrease
in plasma levels (by about 90%) is much greater than that which
would be predicted on the basis of in vitro adsorption studies.
However, Wagner (1966) studied a commercial preparation
(Kaopectate) and it-may be that other ingredients contribute
to the dramatic decrease in blood levels. Therefore, in vitro
data cannot be.disregarded but, at the same time > should not
be extrapolated to in vivo drug effects. The final proof must
come from carefully control studies in man.
This abstract represents the true contents of the thesis
submitted.
Supervisor
- iv -
TABLE OF CONTENTS
Page
I. INTRODUCTIONS 1
I I. LITERATURE . SURVEY ^ ' 4
1. Kaolin 4
. . . . .. ^ . . . . . .. i ... i . . . . . .. .
2. Theory • 10
. . . . . . . . .. i ^ ... ^ . . . . . .. i . . . . .. .
3. Adsorption of Drugs by Kaolin ............... 15
(a) In. Vitro .Adsorption .Studies ............ .15
(b) In Vivo Adsorption Studies ............. 21
4. The Test Drugs 23
. . . . .. ^ . . . . . . . . . . . . . .. i ... i .
(a) Tetracycline Hydrochloride (TC-HC1) .... 23
(b) Neomycin Sulfate (NC-S0 ) 27
4
(c) Lincomycin Hydrochloride (LC-HC1) ...... 31
(d) Chloramphenicol (CM) 33
(e) A m p i c i l l in Trihydrate (AM) 36
I I I. EXPERIMENTAL 39
1. Apparatus 39
2. Chemicals and Reagents ...................... 41
3. Preparation of The Solutions Use in The
Experiment 42
4. Analysis and S t a b i l i ty Characteristics
of The Test Drugs 43
. . . . . .. i....... i ... ^ . . . . .. .
5. Adsorption Characteristics of The Test Drugs 59
6. Desorption Characteristics of The Test Drugs 61
- V -
Page
IV. RESULTS AND DISCUSSION 64 -
1. Preliminary Evaluation of Kaolin ............ 64
2. "determination : of Equilibrium Times 64
(a) Equilibrium Time for TC-HC1 64
(b) Equilibrium Time for NC-S0 - 65
4
(c) Equilibrium Time :for LC-HC1 ............ • 65
3. The Adsorption and Desorption Characteristics
of The Test Drugs 65
(a) Tetracycline Hydrochloride ............. 65
(li)j Adsorption Isotherm, in Water at
37.0°C. .. v ; .- ... . 65
(2) Adsorption Isotherms in pH 1.2, 3.0>
and 5.0 Solutions ................. 71
(3) Desorption Characteristics of TC-HC1 79
(4) Adsorption Interactions between
Therapeutic Doses of TC-HC1 and
Kaolin 81'
(b) Neomycin Sulfate ....................... 82
(1) Adsorption Isotherm in Water at
37.0°C. 82
(2) Adsorption.Isotherms in pH 1.2, 3.0,
and 5.0 Solutions ................. 86
C3) Desorption. .Characteristics of NC-S0 . 90
4
(4) Adsorption Interactions between
Therapeutic Doses of NC^S0 - and
4
Kaolin ^ 90
(c) Lincomycin Hydrochloride 93
(1) . Adsorption Isotherm in Water at
37.0°C. .. ; ;. 93.
(2) Adsorption Isotherms in pH 1.2, 3.0,
and 5.0 Solutions ................. 93
(3) Desorption Characteristics of LC-HC1 102
(4) Adsorption Interactions between,
Therapeutic Doses of LC-HC1 and
Kaolin i . .• ....... i. . 104
(d) Chloramphenicol . 105
(e) Ampicillin Trihydrate .................. 105
V. SUMMARY AND' CONCLUSIONS 108
VI. REFERENCES ... i ... i . . . . . . . . . . . i . . .i i . . . i ..
APPENDIX i ... i ... ^ .. . i ... i 119
- vii
LIST OF TABLES
Table P age
1 The Effect of Time on The Amount of Tetra
cycline Hydrochloride Adsorbed per Gm. of
Kaolin 66
2 The Effect of Time on The Amount of Neomycin
Sulfate Adsorbed per Gm. of Kaolin ... w ..... . 66
3 The Effect of Time on The Amount of Lincomycin
Hydrochloride Adsorbed per Gm. of Kaolin • •• • • 67
4 Adsorption Data for Tetracycline Hydrochloride
by Kaolin . . . . ; ;.. i ....... i i .. i i .. . i .. 69
5 Adsorption of Tetracycline Hydrochloride by
Kaolin at 37°C. i ... i ... i ....... i. . 73
6 Desorption of Tetracycline Hydrochloride
from Kaolin ^ ^ . 80
7 Adsorption Data for Neomycin Sulfate by
Kaolin ...a. : ... : ... : ....... i i . . 83
8 Adsorption of Neomycin Sulfate by Kaolin at
37°C ..... i w ;.. 89
9 Desorption of Neomycin Sulfate from Kaolin .. 91
10 Adsorption Data for Lincomycin Hydrochloride
by Kaolin ... i ... i ^ ...... i i ... i ...... . 94
11 . Adsorption of Lincomycin Hydrochloride by
Kaolin at 37°C 101
12 Desorption of Lincomycin Hydrochloride
from Kaolin . . . . . . . . . . . . . . . . . . . . . . . . . . . i . . . ;. 103
- viii -
LIST OF FIGURES
Figure Page
1 Diagrammatic sketch of the structure of the
kaolinite layer, after Grunner (1932) 5
2 System of Isotherm Classification ........... 12
3 Tetracycline Degradation 25 .
4 Chemical structure of neomycin§C ............ 28
5 A water bath with a tumbler used to determine
adsorption of drug by kaolin ................ 40
6 Spectral Characteristics of Tetracycline
Hydrochloride 45
7 Spectral Characteristics of Neomycin Sulfate •-• - 48
8 Spectral Characteristics of Lincomycin
Hydrochloride ............................... 52.
9 Spectral Characteristics of Chloramphenicol 55
10 Spectral Characteristics of Ampi^cillin
Trihydrate i.. i ... i i i 57
11 . Adsorption isotherm at 37°C. for tetracycline
hydrochloride by kaolin,suspended in water .. 70
12 Langmuir isotherm at 37°C. for tetracycline
hydrochloride by kaolin suspended in water .. 72
13 Adsorption isotherm at 37°C. for tetracycline
hydrochloride by kaolin suspended in pH 1.2,
3.0, and 5.0 solutions .......... ^ .......... . 75
14 Langmuir isotherm at 37°C. for tetracycline,
hydrochloride by kaolin suspended in. pH 3.0
and pH 5.0 solutions 76
15 Freundlich;isotherm at 37°C. for tetracycline
hydrochloride by kaolin suspended in pH 1.2
solution ; 77
i . . . . . . . . . .. i
16 Adsorption isotherm at 37°C. for neomycin
sulfate by kaolin suspended in water ... 84
- ix -
Figure : Page
17 Langmuir isotherm at 37°C. for neomycin
sulfate by kaolin suspended in water . ; . 85
18 Adsorption isotherm at 37°C. for neomycin
sulfate by kaolin suspended in pH 1.2, 3.0,.
and 5.0 solutions ........................... 87
19 Langmuir isotherm at 37°C. for neomycin
sulfate by kaolin.suspended in pH 1.2, 3.0,
and 5.0 solutions 88
20. Adsorption.isotherm at 37°C. for lincomycin
hydrochloride by kaolin suspended in water .. 95
21 Langmuir isotherm at 37°C. for lincomycin .
hydrochloride by kaolin suspended in water .. 96
22 Adsorption isotherm at 37°C. for lincomycin
hydrochloride by. kaolin suspended in pH 1.2,
3.0, and 5.0 solutions 97
23 Langmuir isotherm, at 37°C. for lincomycin
hydrochloride by kaolin suspended in pH 3.0
solution 98
. ... i i ..i ... i ... i ... i ... i ... i . . . . .. .
24 Langmuir isotherm at 37°C.•for lincomycin
hydrochloride by kaolin suspended in pH 5.0
solution .................................... 99