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1

Pharmaceutical Suspensions

Robert A. Nash

St. John's University, Jamaica,New York

u i a us n 1
v f he su ie have a earedin the literature 2-7. An useful discussionof

the topic must also take intoaccountthe importanceof suspensionsto both food and
cosmeticformulations. In addition, much isowed to the paint industry for our current
understandingof the formulation and manufactureof physically stable suspensions.At
the start, a working definition of the term "suspension"will be provided in connection
WIt e more genera erm tsperston,or isperse sys em.

the internal or suspended phase is dispersed uniformly with mechanical agitation through-
out e externa p ase, ca e e suspen ing me ium or ve ic e. e inerna p ase,
consistingof a homogeneousor heterogeneousdistribution of solid particles having a
specific rangeof sizes, is maintaineduniformly in time throughoutthe suspendingve-
hicle with the aid of a single or a particular combinationof suspendingagent(s). In
addition, unlike a solution, the suspendedparticlesexhibit a minimum degreeof solu-
bility in the externalphase. When the suspended solids are less than about I urn in size,
t e systemIS re erre 0 as aco 01 a suspension. en e par ic es aregreaer an

limit for individual suspendablesolid particles in coarsesuspensionsis approximately
to urn en one or more0 e ype 0 so i par ic es a cons i u e e

internal phase arepharmaceuticallyuseful and/or physiologically active, the systemis
known as apharmaceuticalsuspension.

When theparticlesof the internal phase aresphericalor liquid droplets and are
dispersedthroughouta liquid external phase,the system iscalled an emulsion. Even
though theparticlesmay be liquid only atelevatedtemperatures(say 50-80°C)and are
semisoi or rigi a 0 pe au, s i u n ca e
microsco ic examinationthe are enerall consideredto be emulsified rather than
suspended.Thus, a clue to thepresenceof a suspendedparticle is its lack of spheric-

Page 2

2 Nash

The wide ran e of sus ensions as aarticular class or t e of disersion or dis-

ity or its definitive lattice structure.The exceptionsto this general rule are spherical
. ,. . i i r par ic es.

persedsystem, isclassifiedin Table I based on the physical statesof matter (i .e., gas,
liquid, solid) for both the internal andexternalphase ofdispersedsystems.

II. THE PHARMACEUTICAL SUSPENSION

A. Oral Suspensions

efficient wettability (water understood)to build rapid suspendabilitywith minimal ex-
terna y appre agitanon.

B. Topical Suspensions

Historically, the externally applied "shake lotion" is the oldestexampleof a pharma-
ceutical suspension.Calamine lotion USP, as well as otherdermatologicalpreparations,
are closely associatedwith the technicaldevelopmentof the pharmaceuticalsuspension

Table 1 Classificationof Dispersions

Internal External

Gas
Gas
Gas
Liquid
Liquid

Gas
Liquid
Solid
Gas
Liquid

Mixture (air)
Foam
Adsorbate
Wet spray (fog)
Emulsion

Solid
Solid

Gas
Liquid

Dry spray (smoke)
Suspension

Page 244

Reconstitutable Oral Suspensions 247

stitution. This rules out severalcommonsuspendingagentsbecausemany require hy-
rattan, e evate temperatures,or ig searrmxmg or adequate ispersion.Some

suspendingagentsthat are notrecommendedinclude agar, carbomer,and methylcellu-
lose [2]. Although both methylcelluloseand aluminum magnesiumsilicate are not rec-
ommended[2], they have been usedsuccessfullyin a cephalexin[4] and erythromycin
ethylsuccinate[5] formulation, respectively.

Table 4 lists suspendingagentsrecommendedfor use in suspensionsfor reconsti-
u IOn e IOnIC c argesa e agens are me u e orpurposesa avoi mg
hemic 1 in am atibiliti s with other in redients.

The combinationof microcrystallinecelluloseand sodiumcarboxymethylcellulose
is a commonsuspen i agen . a en ra ions0 e com ina iongreaer an 0
in the reconstitutedproductcan result in thixotropic gels. Thisagent,and sodiumcar-
boxymethylcellulosealone, are anionic; they areincompatiblewith many cationic ingre-
dients.

The naturalgums are usually anionic and includeexudatesof tree andextractsfrom
seaweed.Acacia and tragacanthhave been used assuspendingagentsfor many years... .

The carra eenanand al inate susendin a ents areseaweedextracts.The al inates
producehighly viscoussolutionsand theiota-carrageenansproducethixotropic disper-. . .. ..
strength,and hydration rate.

Xanthangum is a common suspendingagent in suspensionsfor reconstitution.
Becauseit is producedby microbial fermentationthere is goodbatch-to-batchunifor-
mity and fewmicrobial problems.Its solution viscosity is practically independentof pH
and temperature.

terminedfor each suspendingagent. Combinationsof suspendingagentshave alsobeen
used. Additional information about these andother suspendingagentsis available in
Chapter4 of this volume [6].

Table 4 SuspendingAgents Suitable for Use inSuspensions
for Reconstitution

gent

cacia
Carbox meth lcellulose sodium
Iota carrageenan
Microcrystallinecellulosewith
carboxymcthylcellulosesodium
Povidone
Propyleneglycol alginate
Silicon dioxide, colloidal

Tragacanth
Xanthangum

Source: Refs. 1 and 2.

o

o

Page 245

248 Ofner et a/.

weetener

e sweetenerIS a srgru icant component0 suspensions or reconsntuuon.

taste. Sweeteners can mask the unfavorable taste and enhance patient acceptance in the
pediatric population that uses this product. Any increased viscosity as a result of the
sweetener aids suspension of the drug particles.

Sucrose can perform both above functions of sweetener and suspending agent, and
serve as a diluent in the dry mixture. In addition, sucrose can be milled to increase its

E. Wetting Agents

Hydrophilic drugs are readily wetted by an aqueous vehicle. These drugs can usually
be incorporatedinto suspensions without the use of a wetting agent. Many drugs in
suspension, however, are hydrophobic; they repel water and are not easily wetted.

ur actants are commonly used toar m the dispersion of hydrophobic drugs. The

formulator selects the appropriate wetting agent for optimum dispersion of the drug at
t e owest e ecnve concentration. Excess wettmg agent can producefoaming and im-
part an unpleasant taste. The Hiestand method[8] of comparing wetting ability between
surfactants can be used for the determination of the appropriate agent. A narrow hydro-
phobic trough holds the powder at one end while asolutionof the wetting agent is placed

der.
IS a common wetting agent. ItIS nonionic and is chemically com-

�~ 0.1%. Another common wetting agent is sodium lauryl sulfate. This agent is anionic
and may be incompatible with cationic drugs.

F. Other Ingredients

The ingredients described in this section include buffers,preservatives,flavors, and
co ors. occu atmg agents are not common y use m suspensions orreconsnrunon

Buffers are used to maintain the optimum pH for all ingredients. Suspension pH is
o ten ajuste to ensure t at t e rug remams mso u e. e po ymeric suspen mg
agents, however, have the greatest viscosity at the pH of their maximum solubility. The
suspending agent should be stable at the pH of the system for the shelf life of the prod-
uct. Certain preservatives, such as sodium benzoate, are most effective at low pH val-
ues in which the molecule is un-ionized. Sodium citrate is a common buffer used in
suspensions for reconstitution.

reservarves are require m most suspensions ecause t e suspen mg agents an
. .

Page 488

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