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Research J. Pharma. Dosage Forms and Tech.

2013; 5(2): 51-55 Praneta Desale

Pharmaceutical Suspensions: Pharmacist has the


Very Best Possible Formulation for the Job at
Hand.
Praneta Desale
Ph. D. Scholar, Department of Pharmacy, CMJ University, Shillong,
Meghalaya -793003, India.

ISSN 0975-234X
Research Journal of Pharmaceutical ABSTRACT:
Dosage Forms and Technology. 5(2):
The proper design and formulation of a dosage form requires consideration
March- April, 2013, 51-55
of the physical, chemical and biological characteristics of all of the drug
substances and pharmaceutical ingredients to be used in fabricating the
product. The drug and pharmaceutical materials utilized must be compatible
with one another to produce a drug product that is stable, efficacious,
attractive, easy to administer and safe. The product should be manufactured
under appropriate measures of quality control and packaged in containers
that contribute to product stability. The product should be labeled to
promote correct use and be stored under conditions that contribute to
Review Article maximum shelf life.

Methods for the preparation of specific types of dosage forms and drug
delivery systems are described in subsequent chapters. This chapter presents
some general considerations regarding pharmaceutical ingredients, drug
product formulation, and standards for good manufacturing practice.

INTRODUCTION:
Suspensions are an important category of pharmaceutical formulation and
present many challenges to formula development personnel because of their
inherent instability of structure and manufacturing and packaging problems.
Suspensions may be meant for oral administration, external application or
parenteral use. They generally consist of a finely divided solid (individual
particles ranging in size from 0.5 to 5.0µ) suspended in a liquid or semi-solid
*Corresponding Author: vehicle which constitutes the continuous phase. Many suspensions are these
Praneta Desale days marketed as dry powders which are ‘constituted’ before use by
Ph. D. Scholar, incorporation of specified amounts of a vehicle. Such ‘suspensions’ are
Department of Pharmacy, produced mainly on account of considerations of stability.
CMJ University, Shillong,
Meghalaya -793003, India. The particle size of the disperse phase is a very important consideration in
suspension formulation. Suspensions for topical application should have
very small particle size to avoid a gritty feel on application and to provide
greater coverage and protection to the area to which the suspension is
applied. In case, the solid substance is meant for skin penetration, its small
size will give a quicker rate of dissolution and hence of the penetration. In
suspensions, meant for introduction into the ophthalmic cavity, the particle
size should not go beyond 10µ. Below this size the patient feels no pain but
above this the suspension may give a feeling of pain or discomfort.
Received on 15.03.2013 Injectable suspensions should have a particle size that can easily pass
Modified on 25.03.2013 through the syringe needle. The needle shaped particles generally give a
Accepted on 02.04.2013
sustained action and hence are preferable in ‘depot’ type products.1
© A&V Publication all right reserved

51
Research J. Pharma. Dosage Forms and Tech. 2013; 5(2): 51-55 Praneta Desale

TYPES OF SUSPENSIONS the container and possess a uniform distribution of


1. According to the route of administration particles in each dose. Controlled Flocculation from
 Oral suspensions should be taken by oral route and stability point of view a suspension in which all the
therefore must contain suitable flavoring and particles remain discrete are regarded to be stable,
sweetening agents. However in pharmaceutical suspension solid particles are
 Topical suspensions meant for external application coarser and sedimentation is due to size of the particles.
and therefore should be free from gritty particles. The electrical repulsive forces between the particles allow
 Parenteral suspensions should be sterile and should to form a closely packed sediment at the bottom, whereas
possess property of syringability. the smaller particles fills within the voids of larger
 Ophthalmic suspensions should be sterile and should particles leaving a cloudy supernatant liquid due to
possess very fine particles colloidal particles. The particles, which form the lowest
layer in the pack, are pressed by the weights of the
2. According to nature of dispersed phase and particles above them thus overcoming the repulsive
methods of preparation barrier. Whereas in the case of particles in the secondary
The suspensions are classified as suspensions containing minimum, which is a desirable state for a pharmaceutical
diffusible solids, indiffusible solids, poorly wettable suspension, the particles form a lose aggregates known as
solids, precipitate forming liquids and products of floccules. The sedimentation of floccules is rapid leading
chemical reactions. to loosely packed high volume sediment which are easily
redispersible.
3. According to nature of sediment
 Flocculated Suspensions,  Rheological Behaviour
In this type the solid particles of dispersed phase aggregate Plastic or pseudoplastic flow is exhibited by flocculated
leading to network like structure of solid particles in suspension depending upon concentration. The apparent
dispersion medium. The aggregates form no hard cake. viscosity of flocculated suspensions is high when applied
These aggregates settle rapidly due to their size as rate of shearing stress is low but decreases as the applied stress
sedimentation is high and sediment formed is loose and increases and the attractive forces resulting in flocculation
easily redispersible. The suspension is not elegant, as are overcome. The dialant flow is exhibited by the
dispersed phase tends to separate out from the dispersion concentrated deflocculated suspensions. The apparent
medium. Therefore it is desired that flocculation should viscosity is low at low shearing stress however it increases
be carried out in a controlled manner so that a balance as the applied stress increases. The rheological
exists between the rate of sedimentation and nature of consideration are of interest to investigate the viscosity of
sediment formed and pourability of the suspension. a suspension as it affects the settling of dispersed particles,
transformation of flow properties while a suspension is
 Non-flocculated Suspensions shaken and product is poured out of bottle and the lotion
In this type the solid particles exist as separate entities in when it is applied to effected area. 3
dispersion medium. The sediments form hard cake. The
solid drug particles settle slowly as rate of sedimentation APPLICATIONS OF SUSPENSIONS
is low as sediments are formed eventually there is  Drugs that have very low solubility are usefully
difficulty of redispersion. The suspension is more elegant formulated as suspensions.
as dispersed phase remain suspended for a long time  If people have difficulty swallowing solid dosage
giving uniform appearance. 2 forms, the drug map need to be dispersed into a
liquid form.
APPROACHES FOR DEVELOPING SUSPENSIONS  Drugs that have an unpleasant taste in their soluble
 Structured Vehicles form can be made into insoluble derivatives, and
The approach employed in the preparation of physically formulated as a suspension, which will be more
sable suspensions involve the use of structured vehicle so palatable. For example chloramphenicol (soluble),
that particles remain deflocculated and applying the chloramphenicol palmitate (insoluble.)
principles of flocculation to produce floccules that settle  In oral suspensions the drug is delivered in finely
rapidly with ease of dispersibility with a minimum divided form, therefore dissolution occurs
agitation. Structured vehicles act by entrapping the immediately in the gastrointestinal (GI) fluids. The
deflocculated particles so that no settling occurs. rate of absorption of a drug from a suspension is
Practically some degree of sedimentation usually takes usually faster than when delivered as a solid oral
place. The Shear-thinning property of these vehicles dosage form, but slower than the rate from solution.
facilitates the reformation of a uniform dispersion when The rate of availability of drug from as suspension is
shear is applied. Thus the product must flow readily from
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Research J. Pharma. Dosage Forms and Tech. 2013; 5(2): 51-55 Praneta Desale

dependent on the viscosity; the more viscous the  DLVO Theory


product, the slower the release of drug. According to DLVO (Derjaguin Landau and
 Insoluble forms of drugs may prolong the action of a overbeek) theory, in a dispersed system the
drug by preventing rapid degradation of the drug in interactions involved between particles are electrical
the presence of water. repulsion and van der walls attraction. The total
 When the drug is unstable in contact with the vehicle, potential energy of interaction is addition of these
suspensions are prepared immediately prior to parameters. 5
handing out to the patient in order to reduce the
amount of time that the drug particles are in contact
with the dispersion medium. For example with FORMULATION OF SUSPENSIONS
ampicillin suspension, water is added to powder or The three steps that can be taken to ensure formulation of
granules, prior to giving out to the patient. A 14- day an elegant pharmaceutical suspension are:
expiry date is given, if kept in the fridge. 4  Control particle size. on a small scale, this can be
done using a mortar and pestle, to grind down
PROPERTIES OF A GOOD PHARMACEUTICAL ingredients to a fine powder
SUSPENSION  Use a thickening agent to increase viscosity of
 There is ready redispersion of any sediment produced vehicle, using suspending agents of viscosity-
on storage. increasing agents
 After gentle shaking, the medicament stays in  Use a wetting agent. 6
suspension long enough for a dose to be accurately
measured. PRESERVATION OF SUPENSIONS
 The suspension is pourable. Water is the most common source of microbial
 Particles in suspension are small and relatively contamination. All pharmaceutical preparations that
uniform in size, so that the product is free from a contain water are therefore susceptible to microbial
gritty texture. growth. Also the naturally occurring additives such as
acacia and tragacanth may be sources of microbes and
THEORIES INVOLVED IN DISPERSE PHASE spores. Preservative action may be diminished because of
 Interfacial phenomenon adsorption of the preservative onto solid particles of drug,
Smaller solid particles are used to disperse in a or interaction with suspending agents. Useful
continuous medium. Smaller particle size and large preservatives include chloroform water, benzoic acid and
surface area is associated with a surface free energy hydroxybenzoates.
making it thermodynamically unstable. Thus the
particles possess high energy which leads to grouping THE DISPENSING OF SUSPENSIONS
together to reduce surface free energy thus leading to The method of dispensing of suspensions is the same for
formation of floccules. These floccules are held most, with some differences for specific ingredients.
together among themselves and within by weak van  Crystalline and granular solids are finely powdered in
der walls forces. However in cases where particles the mortar. The suspending agent should then be
are adhered by stronger forces to form aggregates added and mixed thoroughly in the mortar. Do not
forming hard cake. These phenomena occur in order apply to much pressure, otherwise gumming or caking
to make system more thermodynamically stable. In of the suspending agent will occur and heat of friction
order to achieve a state of stability the system tend to will make it sticky.
reduce the surface free energy, which may be  Add a little of the liquid vehicle to make a paste and
accomplished by reduction of interfacial tension that mix well until smooth and free of lumps. Continue
is achieved by use of surfactants. with gradual additions until complete. 7,8
 Electrical double layer and zeta potential
Most surfaces acquire a surface electric charge when STABILITY OF SUYSPENSIONS
they come in contact with aqueous surface. A solid The physical stability of a pharmaceutical suspension is
charged surface when in contact with an aqueous the condition in which the particles do no aggregate and in
medium possesses positive and negative. which they remain uniformly distributed throughout the
dispersions. In order to achieve this ideal situation the
The equation of stokes’ law reflects that larger suspension should have additive, which are added to
particles exhibit greater velocity of sedimentation. achieve ease in resuspension by a moderate amount of
The velocity of sedimentation is inversely agitation. Taking a case example; In case of dispersion of
proportional to the viscosity of dispersion medium. positively charged particles that is flocculated by addition
of an anionic electrolyte like monobasic potassium
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Research J. Pharma. Dosage Forms and Tech. 2013; 5(2): 51-55 Praneta Desale

phosphate. The physical stability of the system is PREPARATION OF SUSPENSIONS FORM DRY
enhanced by addition of carboxymethylcellulose, Carbopol POWDERS AND GRANULES FOR
934, veegum, tragacanth or bentonite either alone or in RECONSTITUTION
combination. No physical incompatibility is recorded as Suspensions may be prepared from previously
majority of hydrophilic colloids are negatively charged manufactured dry powders or granules if the liquid
and are compatible with anionic flocculating agents. When preparation has a limited shelf life because of chemical or
a flocculated suspension of negatively charged particles physical instability. Powders should firstly be loosened
with a cationic electrolyte is prepared (aluminum chloride) from the bottom of the container by lightly tapping against
the addition of hydrocolloid may result in an incompatible a hard surface. The specified amount of cold, purified
product resulting in stingy mass, which has no suspending water should then be added, some times in two or more
action, and settle rapidly. In such a condition protective portions, with shaking, until all the dry powder is
agent is added to change the sign on the particles from the suspended. The container is usually over-sized in order to
negative to positive is employed which can also be allow adequate shaking for reconstitution. Some
achieved by the adsorption onto the particle surface by suspensions may be prepared by the patient immediately
fatty acid amine or gelatin. Thus an anionic electrolyte is before taking from individually packed sachets of powder
used to produce floccules that are compatible with or from bulk solids.
negatively charged suspending agent. 9
CONTAINERS FOR SUSPENSIONS
QUALITY CONTROL TESTS FOR SUSPENSIONS Suspensions should be packed in amber bottles, plain for
 Sedimentation volume internal use and ribbed for external use. There should be
Redispersibility is the major consideration in adequate air space above the liquid to allow shaking and
assessing the acceptability of a suspension. The ease of pouring. A 5 ml medicine spoon or oral syringe
measurement of the sedimentation volume and its should be given when the suspension is for oral use
ease of redispersion form two of the most common
basic evaluative procedures. The sedimentation SPECIAL LABELS AND ADVICE FOR
volume is the simple ratio of the height of sediment to SUSPENSIONS
initial height of the initial suspension. The larger the The most important additional label for suspensions is
value better is the suspendability. ‘Shake well before use’, as some sedimentation of
medicament would normally be expected. Shaking the
 Particle size and size distribution bottle will redisperse the medicament and ensure that an
The freeze-thaw cycling technique used to assess accurate or aliquot does can be measured by the patient.
suspension for stress testing for stability testing result
in increase of particle growth and may indicate future “Store in a cool place.’ Stability of suspensions may be
state after long storage. It is of importance to study adversely affected by extremes and variations of
the changes for absolute particle size and particle size temperature. Some suspensions, such as those made from
distribution. It is performed by optical microscopy, reconstituting dry powders, may need to be stored in the
sedimentation by using Andreasen apparatus and refrigerator.
Coulter counter apparatus, none of these methods are
direct methods. The sedimentation method yields a Extemporaneously prepared and reconstituted suspensions
particle size relative to the rate at which particles will have a relatively short shelf life. They are usually
settle through a suspending medium. required to be recently or freshly prepared, with a 1-4
week expiry date. Some official formulae state an expiry
 Rheological studies date, but many do not. The pharmacist may have to make
Rheologic methods can help in determining the judgments about the expiry date for a particular
settling behaviour of the suspension. Brookefield preparation, based on its constituents and likely storage
viscometer with variable shear stress control can be conditions. The manufacturer’s literature for reconstituted
used for evaluation viscosity of suspensions. It products will give recommended storage conditions. 11,12
consist of T-bar spindle which is lowered into the
suspension and the dial reading is noted which is a CONCLUSION:
measure of resistance the spindle meets at various This paper will consider how suspensions can best be
levels in the suspension. This technique also evaluated to see how well they meet the purpose for which
indicates in which level of the suspension the they were designed. The performance check of
structure is greater due to particles aggregates. Data suspensions will not be reviewed from the standpoint of
obtained on aged and stored suspension reveals the control chemist who is following a standard set of
whether changes have taken place. 10 procedures on a series of production samples and whose
54
Research J. Pharma. Dosage Forms and Tech. 2013; 5(2): 51-55 Praneta Desale

curiosity and need are generally satisfied when he has a


yes or no answer. Rather, suspensions will be examined at
the research and development stage in their evolution and
through the eyes of the pharmacists who want to be certain
that they have the very best possible formulation for the
job at hand.

REFERENCES:
1. Howard C. A., 1981., Introduction of Pharmaceutical Dosage
Forms (Lea and Febiger, Philadelphia, PA), pp. 139-166
2. Habib M.J., and Mesue R., 1995, Development of controlled
release formulations of ketoprofen for oral use. Drug
Development and Industrial Pharmacy, 2112, 1463-1472
3. Kawashima Y., lwamoto T., Niwa H., Takeuchi H. and ltoh Y.,
1991, Preparation and characterization of new controlled release
ibuprofen suspension for improving suspendability.
International J. of Pharmaceutics, 75, 25-36
4. Dalal P. S., and M. M. Narurkar, 1991, In vitro and in
vivoevaluation of sustained release suspensions of ibuprofen.
International J.of Pharmaceutics, 73, 157-162
5. Bhalerao S. S., Lalla J. K. and Rane, M. S., Study of processing
parameters influencing the properties of Diltiazem
hydrochloride microspheres, J. Microencapsulation, 18’3 2001,
299-307
6. Delgado A., Gallardo V., Salcedo J., and Gonzalez Caballero F.,
1990, Study of electrokinetic and stability properties of
nitrofurantoin suspensions. Part l. Electrokinetics. J. of
Pharmaceutical Sciences, 79, 82-86.
7. Bhalerao S. S., Lalla J. K. and Rane M. S., A study of
electrokinetic and stability properties of suspensions of
Diltiazem hydrochloride microspheres, Indian Drugs, 389 2001,
464-467
8. N.K. Patel, L. Kennon, and R.S. Levinson Pharmaceutical
suspensions, In: Theory and Practice of Industrial Pharmacy
(L.Lachman, H.A. Lieberman, J. L. Kanig. Eds), Lea & Febiger,
Philadelphia. 1986, pp. 479-501.
9. G. Zografi, J. Swarbrick and H. Schott, Dispersed Systems In:
Remington’s Pharmaceutical Sciences (A.R. Gennaro, ed),
Mack Publishing Co., Easton, PA, 1990 pp. 257-309.
10. E. N. Hiestand, Theory of coarse suspension formulation, J.
Pharm. Sci., 53:- 18 (1964)
11. Lieberman H.A., Joseph L. K., The theory and Practice of
Industrial Pharmacy. 3rd edition 1990, pp. 479-501
12. Subrahmanyam C.V.S., Text book of physical pharmaceutics,
2nd edition 2000 pp.377-391

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