DISPERSE SYSTEMS

13 DE ALVA, MYCAELA A.
14 DECENA, MARK PAULO D.
15 ENRIQUEZ, FLOEN MICHAEL S.
16 GALVEZ, KRISTINE BERNADETTE S.

Disperse Systems

Main types of liquid preparations containing undissolved or

immiscible drug distributed in a vehicle

Dispersed phase is the substance distributed

Dispersing phase or medium vehicle

Disperse system together.

The particles are usually solid materials that are insoluble to the liquid
medium

In emulsions dispersed phase is a liquid neither soluble or

immiscible with the liquid of the dispersing phase,

Emulsification results in the dispersion of the liquid drug as fine

droplets throughout the dispersing phase

Disperse Systems

Aerosols the dispersed phase may be small air bubbles throughout

a solution or emulsion

Dispersions also consist of droplets of liquid in air

The particles may vary in size from particles visible to colloidal

dimensions of 1.0nm and 0.5m.

Coarse dispersions - dispersions that have coarse particles have 1050m

Fine dispersions particles that are smaller in size 0.5-10m

Includes suspensions and emulsions

Magmas and Gels

Colloidal dispersions particles are in colloidal range

Disperse Systems

particles of Coarse dispersion have the tendency to separate from

the vehicle and settle below the container than do the particles in
fine dispersion

Solids settle to the bottom because of their higher density than of

the medium.

Emulsions contain oils which has generally have less density than
water, therefore they tend to rise up in the preparation.

Complete and uniform redistribution of the dispersed phase is

essential for accurate administration of uniform doses and usually
accomplished by moderate agitation.

SUSPENSIONS

SUSPENSIONS

are defined as preparations containing finely divided drug particles

distributed somewhat uniformly throughout in the vehicle in which
the drug exhibits a minimum degree of solubility.

Ready to Use they are already distributed through a liquid vehicle

Other Preparations dry powders intended for suspension in liquid

vehicles.

If drugs are unstable in the presence of aqueous vehicle, it is usually prepared in

powdered form

for oral suspension

oral suspension

Reasons for Suspension

A. some are unstable in solution but stable in suspension

B. ease of swallowing and flexibility in administration of doses.

C. the disagreeable taste.

Poor tasting drugs are developed to be insoluble in their vehicle

for preparing a palatable liquid dosage form

Ex. Erythromycin Estolate Oral Suspension, USP

The use of insoluble form in suspension reduces taste-masking problems

Oral Suspensions are aqueous preparations with the vehicle flavored

and sweetened to suit the preference of the patient.

Features Desired in a
Pharmaceutical Suspension

(therapeutic efficacy, stability of the components and permanency

of the suspension, esthetic) overall desirable qualities.

Specifics to the suspension

Should settle slowly and re-dispersed upon shaking

Particle size of the suspensiod should remain constant in long periods of

standing

It should pour easily and evenly

Main features depend on the nature of dispersed phase, dispersion

medium and pharmaceutical adjuncts

Sedimentation Rate of Particles

Stokes law.
Many variables:

Doesnt apply precisely to the usual suspension because:

suspensoid is irregularly shaped and various diameters.

They do collide and cause turbulence

May have affinity in dispersion medium

Basic concepts are applicable to possible adjustments to decrease the

rate of sedimentation.

Velocity of fall is greater in: larger particles, greater density of particle

than medium (because if less dense than vehicle, it will float)

Sedimentation Rate of Particles

Rate of sedimentation is reduced: increasing the viscosity of the

dispersion medium, but not too high, as it will be difficult to
redisperse the suspensoid.

It is only used to a modest extent to avoid the difficulties.

The viscosity characteristics of the suspension is not only measured

by the vehicle used, but also the proportion of the solid particles.

Brookfield Viscometer measures the viscosity by the force required to

rotate a spindle in the fluid being tested.

The physical stability of the suspension appears to be more adjusted

by alteration in the dispersed phase rather than changes in its
dispersion medium.

Brookfield Viscometer another

picture in phone

Physical Features of the Dispersed

Phase of a Suspension

Good pharmaceutical suspensions particle size of 1-50m

Particle size reduction is accomplished by:

Dry milling prior to the incorporation in the dispersed phase,

Micropulverization most rapid, convenient, inexpensive methods producing 10-50m.

they are high speed attrition or impact mills that are efficient in reducing powders to the desired
size

Used for oral and topical suspensions

fluid energy grinding or sometimes referred to as jet milling or micronizing

it is used for finer particles under 10m.

Shearing action of high-velocity compressed airstreams on the particles in a confined space.

Particles are swept in a violent turbulence by sonic and supersonic velocities of airstreams and
collide to each other resulting in fragmentation.

Used for parenteral and ophthalmic preparations

Physical Features of the Dispersed

Phase of a Suspension

Spray Drying produces particles of extremely small dimensions

Is a cone shaped apparatus into which a solution of a drug is sprayed

and rapidly dried by a current of warm, dry air circulating the cone.

It is impossible for a pharmacist to achieve a same degree of

particle size reduction using comminuting equipment.

However, micronized drugs are available commercially in bulk,

Eg. Progesterone

Physical Features of the Dispersed

Phase of a Suspension

According to Stokes Equation,

Smaller particle size is beneficial to the stability of the suspension.

Because the rate of sedimentation is reduced thus providing slow and uniform
rate of settling.

Not to small for it may form a compact cake upon settling.

It resists breakup with shaking.

Forms larger aggregates that are larger and less suspendable.

Particle Shape also affects caking and stability

Symmetrical barrel shape are more stable suspensions than needle shaped
particles

Symmetrical Barrel Shape doesnt cake upon standing

(note: needle form tenaciuous sediment cake on standing and cannot be

redistributed.

Ex. Calcium Carbonate.

Method on Avoiding the formation

of the Cake

Formation of less rigid or loose aggregation it is held together by

weak particle-particle bonds.

Floc or Floccule particles that resists complete settling.

But settle more rapidly than fine, individual particles.

they are less prone to compaction than unflocculated particles

Flocs forms higher sediment volume than unflocculated.

The loose structure permits aggregates to distribute readily with small amount
of agitation

Method of Preparing Flocculated

Suspension

It depends on the type of drug and product desired.

Clays are used as flocculating agent in Oral Suspensions

Diluted Bentonite Magma used as flocculating agent.

When clays are unsuitable agents, like for parenteral suspension,

Its structure supports the floc once it is formed

Flocs are produced by alteration in the pH of the suspension.

Electrolytes also acts as flocculating agents,

Reducing the electrical barrier between the particles by forming a bridge so

as link them together.

Concentration between the nonionic and ionic surface acting agents

induce flocculation and increase sedimentation volume.

Dispersion Medium

Sometimes, with highly flocculated suspensions, particles settle too

rapidly to be consistent with what might be termed a
pharmaceutically elegant preparation.

Rapid Settling

hinders the accurate measurement of dosage

Produces unsightly a supernatant layer (for esthetics)

Thus suspending agents are added to lend its structure:

CMC, methylcellulose, microcrystalline cellulose, polyvinylpyrolidone,

xanthan gum and bentonite

They thicken the suspension medium and help suspend the suspensiod.

Dispersion Medium

Polymeric Substances and Hydrophilic Colloids

Must have appropriate tests to show that they do not interfere with the
drugs availability.

They bind medicinal agents causing them to be unavailable or slowly

available for therapeutic function.

The amount of suspending agent must not be too much to render

the suspension too viscous to agitate or pour.

Rheology the study of flow characteristics

Dispersion Medium

Factors that affects the support of the suspensiod to the medium:

Density of the suspensiod, whether its flocculated

Amount of material requiring support.

Solid content of the Oral suspension may vary according to:

Dose of drug to be administered

Ability of the medium to support the concentration of the drug while

maintaining the desirable features of viscosity and flow.

Adult oral suspension = 5mL or 1 teaspoonful

Pediatric Oral Suspension =dose calibrated drops or teaspoon.

Preparation of Suspensions

In preparing a suspension, a pharmacist must be aware of the

characteristics of both the dispersed phase and dispersion medium.

Sometimes, the dispersed phase has the affinity for the vehicle and is
readily wetted by it.

Other drugs, are not penetrated by the vehicle has the tendency to
float or clump together, if that is the case, the powder must be wetted
to make it more penetrable to the dispersion medium.

Ex, Alcohol, Glycerin, Propylene Glycol, and other hygroscopic liquids.

They displace the air in the crevices of the particles dispersing the particle and
finally allowing it to be penetrated.

In large scale preparation, wetting agents are mixed with the particles
by an apparatus such as the colloid mill.

Small Scale Preparation they are mixed with mortar and pestle.

Preparation of Suspensions

Once the powder is wetted, the dispersion medium is added to the

portions of powder and is blended thoroughly before addition of
additional vehicle.

A portion of the vehicle is used to wash the mixing equipment free

of the suspension and bring the suspension to its final volume.

Product is then subjected to the colloid mill to ensure uniformity.

Preservatives are also added against bacterial and mold growth.

Example formula for Oral Suspension

Aluminum Hydroxide - antacid

Sustained Release Suspensions

Sustained release suspensions only have limited success because of

maintaining the sustained release particles in the liquid disperse systems
is quite difficult.

Product research and technology uses the same ways of preparing

tablets and capsules.

Ex. Coated Beads, Drug impregnated wax matrix, microencapsulation and

ion exchange resin complex.

Pennkinnetic System uses the combination of ion exchange resin complex and
particle coating

The system complexes ionic drugs with ion exchange resins resulting in a drug-resin
complex particles and later coated with ethylcellulose.

Liquid Formulations of the coated particles, the drug remains absorbed onto the resin but
slowly released by ion exchange process in the GIT.

Ex. Hydrocodone Polisterex (Tussionex Pennkinetic Extended Release Suspensions,

Medeva)

Extemporaneous Compounding of
Prescriptions

Solid dosage form of the drug and incorporate it in the liquid

product

Difficulty is the lack of ready information on stability of liquid vehicle

Ex. Leucovorin calcium is stable in milk or antacid and unstable in acidic

solutions

It is known that liquid form has higher decomposition rate than solid
forms.

Overcoming the difficulty

Contact the manufacturer

Literature and package insert

International Journal of Pharmaceutical Compounding

Extemporaneous Compounding of
Prescriptions

Formation of Extemporaneous Suspension

Tablets/ capsules are crushed in a mortar and pestle

Vehicle is slowly added to create a paste (Ora Family of preparations)

Slowly diluted to desired volume

Extemporaneous Compounding of
Prescriptions

The extent of the formulation depends on the patient

Neonate no preservatives, colorings, alcohol

Administered through a tube through mouth and directly in stomach

Alcohol alter liver function, gastric irritation, neurologic depression

Aromatic Elixirs are not used as vehicles because it contain alcohol

Same for patients taking depressants for CNS and make the patient ill.

Preservatives -adverse effects on infants

Benzyl Alcohol cause gasping syndrome and deterioration of multiple organs and
death

Propylene Glycol seizures as stupor in some infants

Formulations for infants should be simple and compounded to supply more

than a few days of medication

To maximize stability, air-tight, light resistant container and placed on

refrigerator. Shake well and watch for color changes

Packaging and Storage of

Suspensions

Suspensions should be placed in wide mouth bottles, to have an

adequate airspace above the liquid for shaking and pouring.

Tight containers protected from freezing, excessive heat and light.

Shake well to ensure uniform distribution for proper dosage.

Examples of Oral Suspensions

Antacid Oral Suspensions

Counter the effect of hyperacidity and employed by persons such as

peptic ulcers who must reduce acidity in stomach

Widely employed as OTC for acid indigestion, heartburn and sour

stomach.

To counter GERD.

Antacid preparations composed of water-soluble materials that act

within the GIT to counteract acids and soothe irritated linings of the GIT.

Sodium Bicarbonate

Water-insoluble salts of aluminum, calcium and magnesium

Aluminum hydroxide, aluminum phosphate, dihydroxyaluminum

aminoacetate, calcium carbonate, calcium phosphate, magaldrate,
magnesium carbonate, magnesium oxide and magnesium hydroxide

Antacid Oral Suspensions

Sodium Bicarbonate, calcium carbonate, and magnesium

hydroxide neutralizes acid effectively and magnesium trisilicate and
aluminum hydroxide are less effective and slow.

Each agent has own side effects

Sodium Bicarbonate sodium overload and systemic alkalosis

Magnesium Preparations lead to diarrhea

Calcium Carbonate hypercalcemia and stimulate stomach for acid

secretion or acid rebound

Aluminum Hydroxide constipation and phosphate depletion with

muscle weakness, bone resorption and hypercalciuria

Antacid Oral Suspensions

Heartburn and gastric distress single dose of sodium bicarbonate and

magnesium hydroxide preparation
Acute peptic ulcer and duodenal ulcer -sodium bicarbonate produces
more sodium and magnesium hydroxide induces diarrhea
Thus, combination of magnesium hydroxide and aluminum hydroxide
because Aluminum hydroxide has constipating effects and counter the
effects of the magnesium hydroxide which is diarrhea.
GERD prefer liquid than tablet because it doesnt require time to
disintegrate
It is important for an antacid to act fast because gastric emptying
doesnt allow it much time in the stomach.
FDA requires antacid tablets to disintegrate within 10 minutes in acid
conditons.
Snacks prolong the stay and action of antacid in stomach.

Antacid Oral Suspensions

Antacid liquid forms are pleasantly flavored (peppermint) to

enhance palatability and patient appeal

Shake for redistribution

Large dose is frequently required

Patients prefer to swallow one or two tablespoonfuls of liquid

preparation than to swallow or chew corresponding amount of
tablets.

Antibacterial Oral Suspensions

Antibiotic substances :

Mycin derivatives, tetracycline, sulfonamides and anti-infective agents

or combinations of these

Many are unstable in solution in length of time

Therefore, manufacturers made their products in insoluble froms of the

drug in aqueous suspensions or dry powder for reconstitution for a
stability standpoint

They are also packed with calibrated droppers for infants to assist
delivery

Dispersing phase is aqueous , colored, sweetened, and flavored

Palmitate form of chloramphenicol is selected for the suspension

dosage form for it is water-insoluble and is flavorless that eliminates the
necessity to mask the bitter taste of chloramphenicol

Rectal Suspensions

Barium Sulfate for suspension

Used orally or rectally for diagnostic visualization of the GIT

Mesalamine Suspension

Treatment of Crohn disease and distal ulcerative colitis,

proctosigmoiditis, proctitis.

No longer available but is still compounded by pharmacists

Colocort

Hydrocortisone rectal suspension indicated as adjunctive therapy in

treatment of ulcerative colitis and packaged in single dose enema
desired for self administration

Dry Powder for Oral Suspension

Consists of dry powder mixtures or granules that are intended to be
suspended in distilled water or some other vehicle prior to oral
administration.
for Oral Suspension to distinguish them from prepared suspension
Mostly antibiotics

Contain the antibiotic drug, colorants, flavorants, sweeteners, stabilizing

agents, suspending agents and preserving agents

In reconstitution, pharmacist loosens the powder by tapping it in hard

surface, and then adds designated amount of water and shakes slurry
unit of all of the dry powder has been suspended
Manufactures provide slightly oversized container for easy shaking of
contents
Pharmacists should not eyeball the amount of water to be added to
fill up the bottle.

Dry Powder for Oral Suspension

Erythromycin ethylsuccinate + acetyl sulfisoxazole - tx for acute

middle ear infection caused by strains of Haemophilus Infuenzae

Probenecid + ampicillin = tx for uncomplicated infections caused by

Neisseria gonorrhoeae.

Cholestyramine hyperlipidemia

Dry Powder for Oral Suspension

Barium sulfate Used orally or rectally for diagnostic visualization of the GIT

It is practically insoluble in water and safe in large doses because intestines doesnt
absorb it.

Pharmacist must be careful with other forms of barium, such as its sulfide, and sulfite
because they are soluble and poisonous.

Barium Sulfate is a fine, non-gritty odorless, tasteless, white powder.

When used orally dx for hypo pharynx, esophagus stomach, small intestine and
colon.

It renders the GIT to be opaque in x-rays to reveal abnormalities.

When used rectally, it allows visualization of features of the rectum and colon

Commercially, for diagnostic use, is available as bulk powder with suspending agents
to be reconstituted to an oral suspension or enema.

Enema contains units that are ready-to-use and disposable bags are also available.