THE ADSORPTION OF ATROPINE SULFATE AND SELECTED OPIUM ALKALOIDS AND ...

147 Pages·2009·5.04 MB·English

THE ADSORPTION OF ATROPINE SULFATE AND
SELECTED OPIUM ALKALOIDS
AND SULFONAMIDES
BY KAOLIN
by
HO PANG CHOI
B . S c, UNIVERSITY OF HONG KONG
HONG KONG, 1971
A THESIS SUBMITTED IN PARTIAL FULFILMENT OF
THE REQUIREMENTS FOR THE DEGREE OF
MASTER OF SCIENCE
in the D i v i s i on of P h a r m a c e u t i c al Chemistry
of the F a c u l ty of P h a r m a c e u t i c al Sciences
We accept t h is t h e s is as conforming to the
r e q u i r ed standard
THE UNIVERSITY OF BRITISH COLUMBIA
f. OCTOBER, 19 75
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 cgain shall not be allowed without my
written permission.
Department of kA&AJ^^l /^tSu2^£jL^
The University of British Columbia
2075 Wesbrook Place
Vancouver, Canada
V6T 1W5
Date II OCA..
1
ABSTRACT
The adsorption i n t e r a c t i o ns between k a o l in and c h l o r-
promazine h y d r o c h l o r i d e, codeine phosphate, morphine s u l f a t e,
atropine s u l f a t e, and four sulfonamides were s t u d i ed in v i t r o .
With the exception of chlorpromazine hydrochloride and three
of the sulfonamides, these t e st drugs have been combined w i th
k a o l in i n to a n t i d i a r r h e al p r e p a r a t i o n s.
Due to s o l u b i l i ty problems, the adsorption of the
sulfonamides by k a o l in was i n v e s t i g a t ed in 1:12.5 hydro
c h l o r ic a c id s o l u t i o n. A ll other studies were c a r r i ed out
in water and in pH 1 . 2, 3 . 0, and 5.0 h y d r o c h l o r ic a c id
s o l u t i o ns and at a temperature of 37.0°C. The data for
adsorbed drugs c o u l d, in most i n s t a n c e s, be represented
g r a p h i c a l ly on the b a s is of e i t h er the F r e u n d l i ch or Langmuir
adsorption equations. However, s e v e r al of the adsorption i s o
therms were c l a s s i f i ed according to the system o u t l i n ed by
G i l es and h is co-workers (1960). Desorption studies for
adsorbed drugs were c a r r i ed out in aqueous s o l u t i o n.
Under the experimental c o n d i t i o ns c i t e d, the sulfonamides
were not adsorbed by k a o l i n. A ll other t e st drugs were
adsorbed by t h is c l a y. In g e n e r a l, adsorption v a r i ed w i th the
pH of the adsorption medium. With the exception of atropine
s u l f a t e, the adsorption of chlorpromazine hydrochloride and
the opium a l k a l o i ds appears to be a r e v e r s i b le process. On
the b a s is of data o b t a i n e d, it was estimated that over 90%
of a normal dose of chlorpromazine h y d r o c h l o r i d e, atropine
s u l f a t e, morphine s u l f a t e, or codeine phosphate would be
adsorbed by a normal dose (six gm.) of k a o l in if the drug
and the adsorbent were allowed to e q u i l i b r a te in 40 m l.
of water.
The in v i vo s i g n i f i c a n ce of these r e s u l ts is not known.
However, on the b a s is of in v i vo data for lincomycin hydro
c h l o r i de (Wagner, 1966) and a l i m i t ed number of other drugs,
decreases in plasma l e v e ls f o l l o w i ng concurrent a d m i n i s t r a t i on
of k a o l in c o n t a i n i ng preparations are greater than those that
might be p r e d i c t ed by in v i t ro data. This may, t h e r e f o r e,
imply that the i n c o r p o r a t i on of opium a l k a l o i ds or atropine
s u l f a te i n to a n t i d i a r r h e al preparations c o n t a i n i ng k a o l in is
undesirable but the f i n al proof of such an assumption must
be based on c a r e f u l ly c o n t r o l l ed studies in man.
This a b s t r a ct represents the true contents of the t h e s is
submitted.
Supervisor
1
i ii
TABLE OF CONTENTS
Page
I. INTRODUCTION 1
II. LITERATURE SURVEY 4
1. K a o l in 4
2. Theory of Adsorption 9
3. Adsorption of Drugs by K a o l in 15
4. In Vivo Studies 22
III. THE TEST DRUGS 27
1. Chlorpromazine Hydrochloride 27
2. Codeine Phosphate 29
3. Morphine S u l f a te 31
4. Atropine S u l f a te 34
5. TThe Sulfonamides 36
IV. EXPERIMENTAL 42
1. Apparatus 42
2. Chemicals and Reagents 44
3. A n a l y t i c al Procedures for and S t a b i l i ty
C h a r a c t e r i s t i cs of the Test Drugs 47
4. AAdsorpti>onCGhar.ac^eristi'Gsoc5f tMieTTest
Drugs 65
5. Desorption C h a r a c t e r i s t i cs of the Test
Drugs 67
V. RESULTS AND DISCUSSION 70
1. E q u i l i b r i um Time for the Adsorption
Process 70
2. Chlorpromazine Hydrochloride . 74
iv
Pa?e
(a) Adsorption Characteristics in Aqueous
Solution 74
(b) Adsorption Characteristics in pH 1.2,
3.0, and 5.0 Solutions. 80
(c) Desorption Characteristics of CPZSHCl 86
(d) Adsorption Interaction between
Therapeutical: Doses of CPZ-HC1 and
Kaolin 89
3. Codeine Phosphate 90
(a) Adsorption Characteristics in Aqueous
Solution 90
(b) Adsorption Characteristics in pH 1.2,
3.0, and 5.0 Solutions 94
(c) Desorption Characteristics of CDN-P0 9 8
4
(d) Adsorption Interaction between
TherapeuticaDoses of CDN-PO. and
Kaolin 7 99
4. Morphine Sulfate 100
(a) Adsorption Characteristics in Aqueous
Solution 100
(b) Adsorption Characteristics in pH 1.2,
3.0, and 5.0 Solutions 100
(c) Desorption Characteristics of MOP-SO^ 106
(d) Adsorption Interaction between
TherapeuticaDoses of M©£-SO. and
Kaolin ' 7 106
5. Atropine Sulfate 110
(a) Adsorption Characteristics in Aqueous
Solution 110
(b) Adsorption Characteristics in pH 1.2,
3.0, and 5.0 Solutions 114
(c) Desorption Characteristics of ATP-SC> 118
4
o
V
Page
(d) Adsorption I n t e r a c t i on between
Therapeutic Doses of ATP-SO. and
K a o l in : . .. 118
6. The Sulfonamides 120
VI; SUMMARY AND CONCLUSIONS 122
REFERENCES 128
BIOGRAPHICAL INFORMATION 132
APPENDIXES 133
vi
LIST OF TABLES
Table Page
1 The effect of time on the amount of
chlorpromazine hydrochloride adsorbed per
gm. of kaolin 71
2 The effect of time on the amount of codeine
phosphate adsorbed per gm. of kaolin 72
3 The effect of time on the amount of morphine
sulfate adsorbed per gm. of kaolin 72
4 The effect of time on the amount of atropine
sulfate adsorbed per gm. kaolin 73
5 The effect of time on the amount of
chlorpromazine hydrochloride adsorbed per
gm. of kaolin 73
6 Adsorption data for chlorpromazine hydrochlor-df-.;
ide by kaolin 75
7 Adsorption of chlorpromazine hydrochloride
by kaolin at 37 C 85
8 Effect of five-fold dilution of chlorpromazine
hydrochloride-kaolin suspension with water
on chlorpromazine hydrochloride adsorption .... 88
9 Adsorption data for codeine phosphate by kaolin 91
10 Adsorption of codeine phosphate by kaolin
at 37°C 97
•11 Effect of five-fold dilution of codeine
phosphate-kaolin suspension with water on
codeine phosphate adsorption 99
12 Adsorption data for morphine sulfate by kaolin 102
13 Adsorption of morphine sulfate by kaolin
at 37 C 107
14 Effect of five-fold dilution of morphine
sulfate-kaolin suspension with water on
morphine sulfate adsorption 108
15 Adsorption data for atropine sulfate by kaolin 112
vii
Table Page
16 Adsorption of atropine sulfate by kaolin at 37°C 117
17 Effect of five-fold dilution of atropine
sulfate-kaolin suspension with water on atropine
sulfate adsorption 119
v i ii
LIST OF FIGURES
1 Diagrammatic sketch of the structure of the
kaolin layer 5
2 System of isotherm classification 12
3 Chemical structure of chlorpromazine hydrochloride 2 7
4 Chemical structure of codeine phosphate 30
5 Chemical structure of morphine sulfate 32
6 Chemical structure of atropine sulfate 35
7 Chemical structure of sulfadiazine 38
8 Chemical structure of sulfamerazine 39
9 Chemical structure of sulfamethazine 40
10 Chemical structure of sulfisoxazole 41
11 Constant temperature reaction tank 43
12 Spectral characteristics of chlorpromazine
hydrochloride 48
13 Spectral characteristics of codeine phosphate .... 52
14 Spectral characteristics of morphine sulfate ..... 55
15 Spectral characteristics of r.eineekate derivative
of atropine sulfate 58
16 Spectral characteristics of sulfadiazine 61
17 Spectral characteristics of sulfamerazine 62
18 Spectral characteristics of sulfamethazine 6 3
19 Spectral characteristics of sulfisoxazole 64
20 Adsorption isotherm at 37°C f or chlorpromazine
hydrochloride by kaolin susperidediinwwater 77
21 Langmuir isotherm at 37°C f or chlorpromazine h.
hydrochloride by kaolin suspended in water 78