An Evaluation of the Enteric Properties of Certain Cellulose Derivatives

104 Pages·11.88 MB·English

by  Antonides, Harold James

PURDUE UNIVERSITY
THIS IS TO CERTIFY THAT THE THESIS PREPARED UNDER MY SUPERVISION
BY Harold James Antonldes
AN EVALUATION OF
ENTITLED_________
OF CERTAIN CELLULOSE DERIVATIVES
COMPLIES WITH THE UNIVERSITY REGULATIONS ON GRADUATION THESES
AND IS APPROVED BY ME AS FULFILLING THIS PART OF THE REQUIREMENTS
FOR THE DEGREE OF
Doctor of Philosophy
P rofessor in Charge of Thesis
Head of School or Department
4
?
i f
TO THE LIBRARIAN:----
IS-
THIS THESIS IS NOT TO BE REGARDED AS CONFIDENTIAL.
PHCfPOBSSOH ES CHABGB (
GRAD. SCHOOL. FORM O

AN EVALUATION OF THE ENTERIC PROPERTIES OF
CERTAIN CELLULOSE DERIVATIVES
A Thesis
Submitted to the Faculty
of
Purdue University
by
Harold James Antonldes
In Partial Fulfillment of the
Requirements for the Degree
of
Doctor of Philosophy
June, 1951
ProQuest Number: 27714224
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ACKNOWLEDGEMENT
The author wishes to express his most sincere thanks and
appreciation to Dr* H. G* DeKay, under whose direction this research
was conducted, and to Drs. J. B. Data, J* C. Lottes, and E* Ramstad,
who served on the research advisory committee*
The author is indebted to Drs* V* L* Anderson and R* L* Ander­
son for their interest and cooperation in the statistical portions
of this work*
The author is most grateful for the cooperation of those
graduate students in the School of Pharmacy who served as the sub­
jects for the radiographic portions of this work* Mr* N* R* Wolfe,
who supervised the radiographic work, and Dr* E* B* Harter, who
advised in the interpretation of the radiographs, are especially to
be thanked for their invaluable aid and cooperation*
The author is grateful to the American Foundation for Pharma­
ceutical Education for the grant which made this work possible*
TABLE OF CONTENTS
Page
INTRODUCTORY 1
General 1
Collodion .......... 2
Keratin ............ 2
S a lo l................... 3
Gelatin •♦eeoe» 4
Shellac And Resinous Mixtures ................ 4
Fatty Acids And Derivatives 5
Polymers and Condensation Products 6
Cellulose Derivatives Other Than Collodion •#♦•••••*••••♦•*••** 7
OBJECTIVES................... 8
EXPERIMENTAL « 9
Compounds Evaluated For Enteric Properties . . . . . . . . . . . . . . . . . . . 9
Carboxymethyl Celluloses .......... 9
Carboaymethyl Hydroxyethyl Cellulose . . . . . . . . . . . . . . . . . . . . . 10
Ethyl Hydroxyethyl Cellulose . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
Hydroxyethyl Cellulose . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
Cellulose A cetate 11
Cellulose Acetate Propionate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
Cellulose Acetate Butyrate ............ 12
Cellulose Acetate Stearate 12
Cellulose Acetate Hydrogen Phthalate . . . . . . . . . . . . . . . . . . . 12
Effect Of Solvent Blend On Film Properties . . . . . . . . . . . . . . . 13
Solvent Blends For Preliminary Screening Tests . . . . . . . . . . . . . 14
TABLE OF CONTENTS (Continued)
Page
Preliminary Screening Test For Enteric Coating Formulations*..*♦ 15
S tatistical Analysis Used For Preliminary Screening Test .. .... 32
Discussion Of Preliminary Screening Test ............ 33
Interpretation Of The Preliminary Screening Tests . . . . . . . . . . . . . 44
Preparation Of Coated Tablets For Testing ................... 45
Modified Thompson And Lee Enteric Coated Tablet Disinte­
gration Test ........... . . . . . . . . . . . . . . . . 46
S tatistical Analysis Used For Modified Thompson And Lee Test . , » 57
Discussion Of Modified Thompson And Lee Test . . . . . . . . . . . . . . . . 57
Interpretation Of Modified Thompson And Lee Tests . . . . . . . . . . . . 59
Radiographic Enteric Coated Tablet Disintegration Test . . . . . . . . . 6l
Discussion Of Radiographic Test . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62
Interpretation Of Radiographic Tests . . . . . . . . . . . . . . . . . . . . . . . . . . . 70
Discussion And Correlation Of Test Results . . . . . . . . . . . . . . . . . . 71
SUMMARY AND CONCLUSIONS......................................................... 74
BIBLIOGRAPHY....................... 75
LISTS OF TABLES AND FIGURES
List of Tables
Table Page
1 Formulations For Preliminary Screening Test s . ........... 16
2 Preliminary Screening Tests ........... IB
3 S tatistical Analysis Of Percentages Of Film Removed
In Preliminary Screening Tests ......... 34
4 Repeated Preliminary Screening Tests ............. 3B
5 S tatistics Derived From Preliminary Screening Tests
In Tables 2 And 4 In Teras Of Percentage Values 42
6 Significance Tests For Difference Between Sets Of
Preliminary Screening Tests .......... 43
7 Coating Solution Formulations 47
8 Modified Thompson And Lee T ests 50
9 S tatistical Analysis Of Modified Thompson And
Lee Tests 58
10 Radiographic Tests 67
11 Summarization Of Radiographic Tests ..»*** 70
List of Figures
Figure Page
1 Equipment Used In The Coating Of The Tablets 48
2 Apparatus For The Modified Thompson And Lee Test ••••*»*«» 56
3 Film 1 In Test 6 For Cellulose Acetate Hydrogen Phthalate. 63
4 Film 2 In Test 6 For Cellulose Acetate Hydrogen Phthalate* 64
5 Test 6 For Hydroxyethyl Cellulose 65
6 Test 11 For Hydroxyethyl Cellulose 66
1
AN EVALUATION OF THE ENTERIC PROPERTIES
OF CERTAIN CELLULOSE DERIVATIVES
INTRODUCTORY
General
The study of methods whereby a medicament may be conveyed to the
intestinal tract without being acted upon in the stomach following oral
administration has received the attentions of many investigators» The
earlier investigators found that p ills were ideally suited to this
mode of medication; however, today the various types of tablets and
capsules have replaced the p ills to a great exbent for medication
purposes* The search for a newer, better or more economical agent or
agents which w ill form a protective coating or sheath about or around
the p ill, capsule or tablet to fu lfill this need has continued from
the latter part of the nineteenth century up to the present* This
coating or sheath, as previously described, is more specifically known
as an enteric coating*
An enteric coating may be considered as a non—toxic and inert
coating of such a nature that the medicament or medicaments contained
within the p ill, capsule or tablet i t encloses are released only into
the intestinal tract* Enteric medication is usually employed for one
or more of the following reasons: (l)
a* For drugs whose action is desired in the intestinal tract, but
which would cause emesis if liberated in the stomach, e*g*,
ipecac.
b* For drugs which may cause unnecessary irritatio n of the mucous
membrane of the stomach, e*g*, anthelmintics, creosote.
2
salicylic acid#
ce For substances which may be inactivated by contact with gastric
media, e.g., alkalies, bile preparations, pancreatin.
d* For medicaments specifically for the treatment of the intestinal
tract and which should reach it in concentrated form, e.g .,
santonin, aspidium, intestinal antiseptics*
e« For substances which would interfere with digestion by forming
insoluble compounds with gastric media and/or the products of
gastric digestion, e.g ., salts of heavy metals, tannin,
f . To give a delayed action of the drug, e.g., barbiturates.
Many substances or compounds either alone or in various combi­
nations have been used and tested for enteric properties. These sub­
stances or compounds may generally be grouped in the following manner:
collodion, keratin, salol, gelatin, shellac and resinous mixtures,
fatty acids and derivatives, polymers and condensation products and
cellulose derivatives other than collodion.
Collodion
The first report of an enteric type of coating appeared in 1867,
wherein it was stated that collodion "protected a p ill from solution
in the stomach". (2) Later in 188? Bembeck in his experiments also
used collodion as an enteric coating agent for p ills of naphthalene. (3)
However, no use has been made of it since that period.
Keratin
In 1884 Unna published the results of his work in which he advo­
cated the use of keratin as an enteric coating for p ills. (4) Unna1 s