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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5482_Библиотеки_им_академика_М_И_Перельмана.pdf
255
Dosage Forms
number of applications. If larger volumes are prescribed they
must be dispensed in a number of smaller containers rather
than in one large container.
Eye drops should be dispensed in glass or suitable plastic
containers with a screw cap fitted with a rubber teat and glass
dropper for easy application of the drops or the containers may
be fitted with a narrow nozzle from which the drops can be
directly instilled into the eye. While using, care must be taken
to avoid contamination by touching to the eyes or to the nozzle
of the container. If this precaution is not taken the remaining
solution may be contaminated and become unfit for use. In the
hospital ward or out-patient departments, eye drops should
not be used after one week after first opening of the container
and in the operation theatre a new unopened container should
be used for each patient.
Eye Ointments
These ointments are meant for application to the eye. They
should be sterile and free from irritation. The ointment base
selected for an eye ointment must be non-irritating to the
eye and must permit the diffusion of the drug throughout
the secretions of the eye and must melt close to the body
temperature.
For the preparation of eye ointments the eye ointment base
BP is used. Thus base consists of:
Yellow soft paraffin 80%
Liquid paraffin 10%
Wool fat 10%
In the eye ointment base BP yellow soft paraffin is used.
White soft paraffin is not used because it is prepared by
bleaching the yellow soft paraffin and the bleaching agent may
remain sticking to the base even after careful washing, which if
instilled into the eye may lead to irritation.
The liquid paraffin is used because it reduces the viscosity
of the base thus make it easier to expel from the tube and apply
to the eye.
Introduction to Pharmaceutics
256
Wool fat is included because it ensures satisfactory emulsi-
fication of the solution and helps in the absorption of active
ingredients.
For the preparation of base all the ingredients are melted
together on water bath and filtered through a coarse filter
paper kept in a heated funnel. It is then sterilized at 150°C for
one hour, immediately stored in a container so as to exclude
micro-organisms before use.
The eye ointments can be prepared by two methods:
(a) Tri turation method; and (b) fusion method. These methods
have already been described in detail under the chapter
ointments.
The preparation of eye ointments must be carried out
under aseptic conditions and packing must also be done in
sterile containers which should keep the preparation sterile
until whole of it is used up. For packaging the eye ointments,
previously sterilized tin, aluminium or plastic collapsible tubes
are used. Nowadays eye applicaps are available which contain
only one application of the preparation.
Advantages
Eye ointments have certain advantages over eye drops that in
the case of ointments the ocular contact time is increased and
studies have shown that the ocular contact time is 2 to 4 times
greater in ointments than eye solutions thus prolonged action
of the drug can be produced.
Disadvantages
Eye ointments have disadvantage that·on application it
produces blurred vision for a short time as the ointment melts
and is spread across the lens.
IMMUNOLOGICAL PRODUCTS
Immunology is the study of immunity and preparations used
to produce immunity are called immunological preparations.
All immunological preparations are biological products
257
Dosage Forms
which are administered parenterally to avoid inactivation
of the preparation on oral administration. The exception is
poliomyelitis vaccine which is administered orally. It contains
living viruses which can multiply in the gut.
IMMUNITY
The infection or disease in human beings or animals is caused
by the invasion of pathogenic microorganisms. The power
of the body to resist the effects of invasion of pathogenic
microorganisms is known as immunity and lack of power of
the body to resist infection is called susceptibility.
There are a number of factors which are responsible for
immunity but phagocytosis and antibody formation are most
important.
Phagocytosis: Phagocytosis may be defined as the ingestion
of microorganisms by certain cells of the body whereby
they are rendered harmless. Phagocytosis is caused by
(1) white blood corpuscles (WBC) and the (2) cells of the
reticuloendothelial system. The white blood cells freely
float in the blood and are carried continuously to all the
tissues. When the micro organisms enter the body, more
and more WBC collect at the site of infection and ingest
the invading bacteria, rendering them harmless. The cells of
the reticuloendothelial system present in the blood spaces
of liver and spleen ingest the microorganisms when the
blood stream passes through liver and spleen and render
the microorganisms harmless which are then carried to
lungs where they are disintegrated.
Antibody production: The body does not depend only on the
process of phagocytosis for the destruction of pathogenic
microorganisms. It produces other substances known as
antibodies which destroy the pathogenic microorganisms
and their toxins. Anybodies are highly specific in their
nature and attack either microorganisms or toxins.
Antibodies may be defined as the substances produced
in the body on the invasion of pathogenic microorganisms
either to destroy these pathogenic microorganisms or their
toxins.
Introduction to Pharmaceutics
258
Types of Immunity
Immunity may be classified as follows.
Natural Immunity
It is God gifted immunity which exerts resistance to disease. It
differs between species, races, individuals and ages.
Species: Certain species are immune to some diseases whereas
others are not. For example, man is susceptible but fowls are
not; tuberculosis is very fatal to guinea-pigs but is not so fatal
to man.
Races: Negroes have high resistance to yellow fever whereas
white men are susceptible to it.
Individuals: lt is well known that some persons are more
resistant to cold and skin infections than others.
Age: Most of the children between 2 and 5 years of age group
are susceptible to diphtheria whereas most adults are immune
to it.
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Dosage Forms
Acquired Immunity
Natural immunity is not sufficient to protect the body from
microbial diseases, therefore, additional immunity is acquired
either by the stimulation of the antibody producing cells of the
body (active immunity) or by introducing antibodies formed
from another person or animal (passive immunity).
Active immunity: Active immunity is developed in an individual
due to the formation of antibodies on the introduction of
antigenic substances in the body. It may be naturally acquired
or artificially stimulated.
Naturally acquired active immunity: It is acquired as a result of
natural infection produced by pathogenic microorganisms.
There may or may not be a clinically recognisable disease.
When a patient recovers from certain diseases like diphtheria,
smallpox, poliomyelitis, he is left with a high degree of
immunity which may last for the whole life, however after
influenza, pneumonia and gonorrhea, immunity produced
is short lived. Similarly children living in slum areas acquire
immunity against a number of diseases because they are
exposed to such diseases time and again.
Artificially acquired active immunity: This type of immunity is
acquired by the administration of specific vaccines or toxoids.
When these antigenic substances are introduced into the body,
they stimulate the body to produce antibodies. Thus body
develops its own defence against pathogenic microorganisms.
Passive immunity: This type of immunity is produced by the
introduction of already formed antibodies into the body of
an individual. These antibodies may have been developed in
another individual or even in another species. Though passive
immunity is rapidly produced but it is not long lasting. Passive
immunity may be naturally acquired or artificially produced.
Naturally acquired passive immunity: In this type of immunity
the antibodies are transmitted from the mother to the foetus
through the placental blood. This imparts immunity to
the infant for several months. Antibodies for chickenpox,
diphtheria, measles and scarlet fever are transmitted in this
Introduction to Pharmaceutics
260
way, that is, why the infant shows high resistance against these
diseases only for about six months after which this resistance
is lost.
Artificially produced passive immunity: This type of immunity
is produced by injecting antibody-containing preparations
known as antisera, sera or immune sera. The antibodies are
first produced in an animal usually a horse or occasionally
some other person and then injected into the concerned person.
Related Terms Used in Immunity
Pathogens: These are the infection causing microorganisms.
Antigens: These are the substances which stimulate the
body to produce antibodies.
Antibodies: These are the substances formed in the body in
response to stimulation by antigens.
Toxins: These are the poisonous substances produced by
pathogenic microorganisms and lead to infection or disease
in man or animals.
Exotoxins: These are the toxins which can diffuse freely
through the bacterial cell wall into the blood or the medium
in which the microorganisms are growing.
Endotoxins: These are the toxins which cannot diffuse
through the bacterial cell wall and are retained within the
bacteria. They are released only when the cells die and start
disintegrating.
Antitoxins: These are the substances containing antibodies
produced by the blood, which specifically neutralise the
toxins produced by particular microorganisms.
Sera or immune sera: A clear fluid which separates from blood
when it clots is known as serum. When a serum contains
antitoxic antibodies it is known as antitoxic serum. They
are usually obtained from animals but sometimes from
human serum also.
Toxoids: These are the toxins whose toxicity has been
removed by gentle heat or by chemical treatment but their
antigenic properties are retained, e.g. tetanus toxoid and
Staphylococcus toxoid.
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Dosage Forms
Vaccines: These are the substances which are administered in
the body to produce resistance against infectious diseases.
They are mainly used as prophylactic treatment. Vaccines
may contain living, attenuated or killed bacteria, viruses or
rickettsia.
FORMS OF VACCINES
Simple vaccines: These vaccines contain only one species of
microorganisms
Mixed vaccmes: These vaccines contain two or more than
two species of microorganisms.
Univalent vaccines: These vaccines contain only one strain
of a species.
Polyvalent vaccines: These vaccines contain two or more
strains of the same species of microorganisms.
Immunological Preparations
These are the substances or agents which are used to produce
immunity in an individual. They are mainly used for the pre-
vention of diseases, e.g. vaccines. They are also used for the
treatment of diseases, e.g. antiserums; and also for diagnostic
purposes, e.g. bacterial toxins.
Classification of Immunological Preparations
The immunological preparations may be classified as follows:
Preparations producing active immunity
y Vaccines containing living bacteria, e.g. BCG vaccine.
y Vaccines containing dead bacteria, e.g. cholera, pertussis,
plague and typhoid vaccine.
y Vaccines containing killed rickettesia, e.g. typhus vaccine.
y Vaccines containing living viruses, e.g. measles, small-
pox. poliomyelitis and yellow fever.
y Vaccines containing toxoids, e.g. diphtheria, tetanus
and staphylococcus.
Diagnostic preparations containing bacterial toxins used
for schick test and tuberculin test.
Preparations containing antibodies (antitoxin and anti-
serum) used to produce passive immunity.
Introduction to Pharmaceutics
262
Preparations Producing Active Immunity
Active immunity is produced by injecting antigens into the
body which stimulate the production of antibodies. Antigens
are administered in the form of vaccines. Active immunity
is slowly developed but lasts for a long time. To produce a
desired level of antibodies in the body, a number of injections
of vaccines will have to be admirustered at specified intervals.
The first injection of vaccines produces a low level of immunity.
Active immunization is a prophylactic measure used to protect
an individual against a particular infective disease.
Bacterial vaccines
(a) Vaccines containing living organisms, e.g. BCG vaccine or
Bacillus Calmette–Guerin vaccine
This vaccine was developed by two French scientists,
Calmette and Guerin in 1906. It is a suspension of living cells
of a strain of Mycobacterium tuberculosis known as the Bacillus
of Calmette and Guerin.
Preparation: It is prepared by growing the bacilli Mycobacterium
tuberculosis on a suitable medium for not more than 14 days. The
culture is then transferred to a sterile liquid which prevents the
further growth but preserves the viability and antigenicity of
the vaccine. The vaccine so prepared is transferred, under
aseptic conditions, to sterile glass containers and sealed
immediately.
BCG vaccine is available both in a liquid and a freeze dried
form. The latter is reconstituted immediately before use which
should be used within 2 hours after its reconstitution and the
unused portion must be discarded. The dried vaccine retains
its potency for one year if stored at a temperature of 2° to 10°C.
The liquid vaccine gets deteriorated easily, even if stored at a
low temperature therefore must be used within 14 days from
the date of its manufacture. Due to this reason this vaccine
cannot be tested for its toxic effects because at least six weeks
time is required for its testing therefore the vaccine is supplied
without testing, hence if any untoward reactions are observed
after its use further use of this batch of vaccine must be stopped
immediately.
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Dosage Forms
Uses: This vaccine is used as an immunizing agent against
tuberculosis.
(b) Vaccines containing dead bacteria, e. g. cholera, pertussis, plague
and typhoid vaccine
(i) Cholera vaccine: It is a sterile suspension of killed strains of
cholera vibrio (Vibrio cholerae) in a sodium chloride injection
or other suitable diluent. It is prepared from equal portions
of suspensions of Inaba and Ogawa strains of cholera
vibrio, which are grown separately. The bacteria are killed
either by heating the suspension at 56°C for one hour or by
treating it with a bactericide. The number of killed bacteria
which should not be less then 8000 million bacteria in 1 ml.
The suspension is sterilized by suitable method and then
distributed in sterile ampoules or vials which are sealed
immediately.
Uses: It is used for prophylactic immunization against cholera.
Its effect remains for 3–6 months. It is given by subcutaneous
or intramuscular injection.
(ii) Pertussis vaccine: It is a sterile suspension of killed strains of
Pertussis bacilli (Bordetella pertussis) in a sodium chloride
injection or other suitable diluent. It is prepared by growing
one or more strains of B. pertussis on a suitable liquid
medium for 24 to 72 hours. The bacteria are killed by heating
the suspension at 56°C or by adding a suitable bactericide.
The suspension is centrifuged, the supernatant liquid is
discarded and the deposited bacteria are suspended in a
sodium chloride injection or other suitable diluent isotonic
with blood. The suspension at this stage is very concentrated
which is kept in the cold for about three months to eliminate
abnormal toxicity. This concentrated suspension is then
diluted with sodium chloride injection or other suitable
diluent to get final dilution of the preparation. The number
of killed bacteria are counted in the suspension which
should not be less than 20000 million bacteria in 1 ml.
Uses: It is used for active immunization of children against
whooping cough. It is given by subcutaneous injection.
(iii) Plague vaccine: It is a sterile suspension of killed strains of
Plague bacilli (Pasteurella pestis) in isotonic sodium chloride
Introduction to Pharmaceutics
264
solution or other suitable diluent. It is prepared similar to
pertussis vaccine by growing a strain of P. pestis on a suitable
media. Plague vaccine contains 3000 million bacteria in
1 ml.
Uses: This vaccine is used for immunization against plague.
It is given by intramuscular or subcutaneous injection.
(iv) Typhoid (paratyphoid A and B vaccine): It is a sterile suspension
of killed strains of Salmonella typhi, S. paratyphi A, and S.
paratyphi B. It is prepared similar to pertussis vaccine, from
strains of S. typhi, S. paratyphi A, and S. paratyphi B grown
on suitable culture media. This vaccine is also known as
TAB vaccine. TABC contains S. paratyphi C in addition to
TAB.
Uses: TAB vaccine is used for immunization against typhoid
fever. It is given by subcutaneous injection.
(c) Vaccines containing killed rickettsia, e.g. typhus vaccine
It is a suitable suspension of the killed typhus rickettsia. It
may be prepared by injecting small doses of living organisms
into the yolk sacs of fertile eggs which have been incubated
for seven days. They are again in cubated for 4 to 7 days or
until the yolk sac is heavily infected. The yolk sacs are ground
to liberate maximum number of rickettsia and the material is
suspended in a saline or other suitable diluent isotonic with
blood. The product so obtained is purified by extraction
with solvent ether, to remove fatty matter from the yolk. The
resultant suspension is distributed under aseptic conditions in
sterile containers and sealed immediately.
Uses: This vaccine is used for immunization against diseases
and infections caused by rickettsia. It is given by subcutaneous
injection.
(d) Vaccines containing living viruses, e.g. smallpox, measles,
poliomyelitis vaccine, etc.
(i) Smallpox vaccine: It is a liquid or dried preparation of
vaccinia virus grown on the skin of living healthy sheep or
calves; or in the membranes of the chick embryo.