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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5724_Библиотеки_им_академика_М_И_Перельмана.pdf
225
Dosage Forms
crystalline or amorphous form. Though the drugs are prepared
in many different physical forms and shapes but many of them
are prepared by using powders in one way or the other. Each
dosage form so prepared has certain advantages over the
other form. Similarly, the powders have certain advantages as
described below.
Advantages
Most of the drugs are available in powder forms and it
becomes more convenient for the physician to prescribe
specific amount of medicament according to the need of
the patient.
Powders are usually more stable than liquids because
chemical reactions take place more rapidly in atmospheric
conditions when the drug is in liquid dosage form than
powder.
Incompatibility is less in case of powders than liquids.
The smaller particle size of powders produces more rapid
dissolution in the body fluids than other solid dosage forms
of medicament, e.g., tablets, capsules or pills. The rapid
dissolution increases the blood concentration in a shorter
time, thereby the action is produced in a lesser time.
Large quantities of bulky drugs which are otherwise
difficult to administer can be easily administered by mixing
with liquids.
They are more easy to carry than liquids.
They are more economical as compared to other dosage
forms because for extemporaneous preparation they do not
require any special technique or machinery.
Childien and old persons who cannot swallow solid dosage
forms can easily injest powders which can be dispersed in
water or any other liquid and may be administered through
feeding tube to the patients who are fed by tubes which
terminate in the stomach itself.
Disadvantage
Drugs which deteriorate on exposure to atmospheric condi-
tions are not suitable for dispensing in powder forms.
Bitter, nauseous, corrosive and unpalatable drugs cannot be
dispensed a powder form.
Introduction to Pharmaceutics
226
Deliquescent and hygroscopic drugs cannot be dispensed
in powder form.
Volatile drugs are not suitable for dispensing in powder
form.
Classification of Powders
Simple and compound powders for internal use (divided
powders).
Granular effervescent powders for internal use.
Bulk powders for external use, e.g. dusting powders,
insufflations and tooth powders, etc.
Powders enclosed in catchets and capsules.
Compressed powders (tablets) and tablet triturates.
INSUFFLATIONS
These are the finely divided powders meant for introduction
into the body cavities such as ears, nose, tooth sockets and
vagina with the help of an apparatus known as insufflator.
This divides the powder into a stream of finely divided
particles to the site of application. The major difficulty in using
this apparatus is that (i) it is difficult to obtain a measured
quantity of drug to get a uniform dose; (ii) it has a tendency to
get blocked when the powders used are wet or the apparatus
itself is wet. The introduction of newer pressure aerosols have
eliminated these difficulties. This method has the advantage
that a measured quantity of dose through metered valves is
supplied and the product is also protected.
In insufflations the particle size must be very small and they
should be absolutely free from irritant and sensitizing effects.
DUSTING POWDERS
Dusting powders are meant for external application to the skin
for antiseptic, antipruritic, astringent, antiperspirant, absorbent
protective and lubricant purposes. These powders must be
homogenous and in a very fine state of subdivision to enhance
effectiveness and minimise local irritation. For this purpose
they may be passed through a sieve no. 120. Additionally the
dusting powders should flow easily, spread uniformly and
227
Dosage Forms
stick to the skin when applied. They must be able to protect the
skin from irritation caused by friction, moisture or chemical
irritants.
Dusting powders are generally prepared by mixing two
or more than two ingredients in which starch, kaolin or
talc is used as one of the ingredients of formulation. Starch
being a carbohydrate can support bacterial growth therefore
rarely used. Talcum and other similar substances though are
chemically inert substances but are readily contaminated with
microorganisms like Clostridium tetani, Cl. welchii and bacillus
anthracis. Therefore, they must be sterilized before using in the
formulation otherwise they may be a source of infection.
The dusting powders are dispensed in sifter-top containers
or pressure aerosols. The pressure aerosol containers are
costlier than other containers but can protect the powder from
atmospheric conditions and help in the easy application of
the preparation. Dusting powders may also be applied with
powder puff, a soft brush or a sterile gauze pad but care must
be taken to avoid mechanical irritation to the skin surface.
Though the dusting powders are considered non-toxic but
the inhalation of light, fluffy powders may lead to pulmonary
inflammation of lungs in infants and absorption of boric acid
through the broken skin may cause toxic reactions in infants.
Therefore proper care must be taken while using these types of
preparations.
R
x
Purified talc, sterilised 50 gm
Starch, in powder 25 gm
Zinc oxide 25 gm
Label: Zinc starch and talc dusting powder.
Type: Dusting powder.
EFFERVESCENT POWDERS
Effervescent powders are mixtures of organic acids and alkalis
that release carbon dioxide gas when dissolved in water. This
reaction occurs between the acid and the base, resulting in
the evolution of CO
2
. Some common examples of effervescent
powders include combinations of citric or tartaric acids with
sodium carbonate or bicarbonate.
Introduction to Pharmaceutics
228
Effervescent powders have various uses due to the liberation
of carbon dioxide gas:
Masking bitter and nauseous tastes: The effervescence
caused by the release of CO
2
can help mask unpleasant
tastes associated with certain medications. By creating a
fizzy sensation in the mouth, the powder can reduce the
perception of bitterness or nauseous flavors.
Promoting gastric secretions: The carbon dioxide produced
by effervescent powders can stimulate the production of
gastric juices in the stomach. This can aid in the digestion
process and promote better absorption of certain drugs or
nutrients.
Acting as a carminative: Carminatives are substances that help
alleviate gas and bloating in the digestive system. The release
of CO
2
from effervescent powders can have a soothing effect
on the gastrointestinal tract, relieving discomfort caused by
gas accumulation.
Advantages
Pharmaceutical effervescent powders offer several advantages
compared to other dosage forms. These are:
Enhanced solubility: Effervescent powders are formulated
to dissolve rapidly in water or other liquids. This allows
for better solubility of the active ingredients compared to
conventional tablets or capsules.
Patient compliance: Effervescent powders can improve
patient compliance, especially in individuals who have
difficulty swallowing tablets or capsules.
Customizable dosage: Effervescent powders offer flexibility
in adjusting the dosage strength.
Rapid onset of action: The rapid dissolution and absorption
of effervescent powders can lead to a faster onset of action
compared to other dosage forms. This is particularly
advantageous for medications that require quick relief,
such as analgesics or antacids.
Improved stability: Effervescent powders can provide
improved stability for certain active ingredients.
Enhanced palatability: Effervescent powders often contain
fla vorings or sweeteners, making them more palatable and
enjoyable to consume.
229
Dosage Forms
Versatile formulation options: Effervescent powders allow for
versatile formulation options. They can be easily combined
with a wide range of active ingredients, including vitamins,
minerals, herbal extracts, or combination therapies.
Main Components of Effervescent Powders
Effervescent powders typically consist of several components
that work together to create the desired effervescence and
deliver the active ingredients. These are:
Acidulants: Effervescent powders contain organic acids,
such as citric acid or tartaric acid, which serve as the
acidulants. These acids react with the alkaline component
in the presence of water to release carbon dioxide gas. The
acidulants are responsible for the fizzing or effervescent
action of the powder.
Alkaline salts: Effervescent powders also include alkaline
salts, such as sodium bicarbonate or sodium carbonate.
These salts act as the alkaline component and react with the
acidulants when dissolved in water. The reaction between
the acidulants and alkaline salts generates carbon dioxide
gas, leading to the effervescent effect.
Active ingredients: Effervescent powders can contain various
active ingredients, depending on the intended therapeutic
use. These active ingredients can include drugs, vitamins,
minerals, herbal extracts, or other therapeutic compounds.
The choice of active ingredients depends on the desired
therapeutic effect of the effervescent formulation.
Excipients: Effervescent powders may contain excipients,
which are non-active substances that assist in the manu-
facturing and performance of the powder. Common
excipients in effervescent powders include fillers or diluents,
sweeteners, flavors, colors, stabilizers, disintegrants,
antioxidants and preservatives.
EFFERVESCENT GRANULES
Effervescent granules are the specially prepared solid dosage
form of medicament, meant for internal use. They usually
contain a soluble medicinal agent mixed with citric acid,
tartaric acid, and sodium bicarbonate. Before administration
Introduction to Pharmaceutics
230
they are suspended, dissolved in water or are mixed with soft
drinks. On mixing with water the carbon dioxide is released
as a result of acid-base reaction producing effervescence and
the mixture is taken while effervescing. The carbonated water
produced from the release of carbon dioxide serves to mask the
saline and bitter taste of drugs and the carbon dioxide is said
to stimulate the flow of gastric juice and accelerate absorption
of medicament.
Effervescent granules are preferred to effervescent powders
in order to decrease the rate of dissolution of the substances
upon addition to water. Further, if powders are used there·
may be violent and uncontrollable effervescence with loss of
carbon dioxide and ultimately the carbonation of solution may
decrease to a great extent.
STERILE FORMULATIONS
Parenteral preparations or injectables are the sterile solutions
or suspensions of drugs in aqueous or oily vehicles meant for
introduction into the body by means of an injection under or
through one or more layers of the skin or mucous membrane.
Since they are introduced into internal body compartments they
must be sterile and free from all types of living microorganisms
and microbial products such as toxins, pyrogens, etc., and
should be free from particles like dust, fibres, etc. They should
be isotonic with body fluids. An utmost care must be taken in
the preparation of injectables to avoid all types of physical,
chemical or microbial contaminations.
Parenteral preparations must be introduced through the
same route for which they are intended, for example, if an oily
suspension meant for intramuscular injection is introduced by
intravenous injection may prove fatal. Similarly potent drugs
meant for administration through intramuscular injection may
lead to even death if given by intravenous injection.
ROUTES OF ADMINISTRATION OF
PARENTERAL PRODUCTS
Various routes of administration of parenteral products
(Fig. 5.21) are as follows:
231
Dosage Forms
1. Intracutaneous or intradermal injections: These injections
are given in between dermis and epidermis. Skin of the left
forearm is usually selected for giving the injection. Absorption
by this route is slow therefore usually small volume from 0.1
to 0.2 ml is injected. This route is mainly used for testing the
sensitivity of the injectables and for diagnostic purposes.
2. Subcutaneous or hypodermic injections: These injections are
given in the subcutaneous tissue under the skin of the upper
arm. The volume of 1 ml or less can be injected by this route.
This is the most popular route because it is convenient for the
patient and the doctor.
3. Intramuscular injections: These injections are given into
the muscular tissues. The muscles of the shoulder, thigh or
buttock are usually selected. Generally volume up to 2 ml is
administered by this route and should not exceed 4 ml at one
site.
4. Intravenous injections: These injections are given into the vein
therefore directly reach the blood stream. The median basilic
Fig. 5.21: Routes of administration of parenteral products.
Introduction to Pharmaceutics
232
vein which is near the elbow is usually selected because it is
easily located and connects with the other major veins of the
arm. Large volumes of solutions ranging from 1 ml to 500 ml
or even more can be injected but volumes of more than 15 ml
should be isotonic with blood. Oily injections and suspensions
cannot be injected by this route.
5. Intra-arterial injections: These injections are given directly
into the artery when an immediate effect in a peripheral area is
required. They are occasionally used.
Less Commonly Used Routes
6. Intracardiac injections: They are given directly into the heart
muscles or ventricle and are used in emergency only.
7. Intrathecal injections: They are given into the subarachnoid
space surrounding the spinal cord. This route is used for giving
spinal anaesthesia.
8. Intracimrnal injections: They are given in between the first
and second cervical vertebrae. This route is principally used to
withdraw cerebrospinal fluid for diagnostic purposes.
9. Peridural injections: These injections are given between the
dura mater and the inner aspects of the vertebra, i.e. it is the
area of vertebral canal which does not have dura mater and
its contents. This route is sometimes used for giving spinal
anaesthetics in special cases.
10. Intra-articular injections: These injections are given into the
liquid that lubricates the joints.
11. Intracerebral injections: These injections are given into the
cerebrum.
Advantages
Parenteral route of administration is used when a rapid
onset of action of the drug is required, hence the route is
used in emergency cases.
This route is preferred when the drugs are inactivated in the
GlT or drugs are not well absorbed after oral administration.
This is the most suitable route of administration of drugs in
treating patients who are non-cooperative, unconscious or
are otherwise unable to take the medicine orally.
233
Dosage Forms
Prolonged action of a drug can be successfully produced by
this route. ·
Solutions in volumes from fraction of millilitre to 4 litres
can be introduced by parenteral route.
Disadvantages
This mode of treatment is more expensive because it
requires a technical and trained person for administration.
Sterilization is of utmost importance.
The administration of drug through wrong route of injection
may prove fatal.
Daily or frequent administration of injections may pose
difficulties to the patient.
TYPES OF PARENTERAL PREPARATIONS
Parenteral preparations may be classified as follows:
Solutions ready for injection.
Suspensions ready for injection.
Emulsions suilable for parenteral administration.
Dry, soluble products which are dissolved in a suitable
solvent immediateiy before its administration.
Dry, insoluble products which are combined with a suitable
vehicle just before its administration.
The above mentioned preparations may be administered
by any of the routes such as subcutaneous, intradermal, intra-
muscular, intravenous, intraspinal, intracisternal, intrathecal,
intracardiac, or intra-articular. Out of these routes, the subcuta-
neous, intramuscular and intravenous are the most commonly
used routes of injections for the administration of drugs, but
the nature of the product will determine the particular route of
administration which may be employed. For example, in case
of intravenous injections, the drug in an aqueous solution is
introduced directly into the vein whereas suspensions would
not be introduced directly into the blood stream, because the
insoluble particles of suspensions may block the capillaries.
Subcutaneous injection should contain water soluble and non-
irritating drugs and should be isotonic with body fluids to
avoid irritation and pain. For intramuscular injection the drug
Introduction to Pharmaceutics
234
may be dissolved or suspended in an aqueous or oily vehicle
but the drugs dissolved in aqueous vehicles are absorbed faster
than the drugs in oily solutions or suspensions in oily vehicle.
Essential Qualities of a Parenteral Product
A parenteral product must possess the following characteristics:
It should be free from living microorganisms and microbial
products.
It should be free from pyrogens.
It should be free from foreign particles such as dust, fibres,
etc.
It should be free from chemical contaminants.
It should be isotonic with body fluids.
It should have matching specific gravity with respect to
some body fluids.
Multidose injections must contain preservatives.
Container/closure must not affect the product.
FORMULATION OF PARENTERAL PRODUCTS
In the development of parenteral products the pharmacist
should have thorough knowledge and understanding of the
principles involved and utmost care must be taken regarding
accuracy, cleanliness and overall quality of the product. The
medicinal substances used in the formulation of injections
should be free from microbial and pyrogenic contamination.
Whenever possible special parenteral grades of drugs which
are commercially available should be used.
Only a minimum number of absolutely necessary additives
in smallest possible quantities should be added. Excessive
use of additives in parenteral products should be avoided
since sometimes the metabolism of these additives becomes
a problem. Some of the additives which are commonly
used in the formulation of parenteral products are described
below.
Vehicles
In the development of a parenteral product one will have
to use a suitable vehicle for dissolving or suspending the