C 14 Suspensions

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CHAPTER 14: DISPERSE SYSTEM

Suspension

Is a two-phase system consisting of a finely divided solid

dispersed in a liquid vehicle. The finely divided particles

are also referred to as ‘Suspensoids” .

In these preparations, the substance distributed is

referred to as dispersed phase and the vehicle is

termed the dispersing phase or dispersion medium.

Together, they produce a dispersed system.

Dispersions containing coarse particles, usually 10 to 50

um in size, are referred to as coarse dispersion.

Dispersions containing particles of smaller size are

termed fine dispersions (0.5 to 10 um)

In general sense, Suspension may include:

1. Gels

2. Lotions

3. Magmas & Milk

4. Mixtures

Characteristics of Oral Suspension

Particles should be small uniform sizes that do not settle

rapidly

The particles that do settle to the bottom of the

container should not pack in to a hard cake & should

be re-dispersed completely and evenly with a minimum

amount of agitation

Characteristics of Suspension

Should not be too viscous to pour freely from the mouth

of the bottle

Should have an agreeable odor, color and taste &

must not decomposed or support mold growth during

storage

Must have therapeutic efficacy

Suspensions for injections must contain particles size

such that they can pass freely through the syringe

needle called “syringeability”.

Ophthalmic suspension should be formulated such that

the particles do not exceed 10 microns. Below this size,

the patient experiences no pain when instilled into the

eyes.

For Topical use, fine particles are desired to avoid

grittiness when applied to the skin. The smaller the size,

the greater the covering and protective power of the

preparation

Reasons for Suspension

Certain drugs are chemically unstable when in solution

but stable when suspended.

Suspension insures chemical stability while permitting

liquid therapy.

Many patients prefer liquid form than solid forms for

swallowing.

Convenience in administration of usually large doses

Safety and convenience of liquid doses for infants and

children.

Disagreeable taste of certain drugs when given in

solution is negligible when the drug is administered as

undissolved particles of a suspension, e.g

chloramphenicol

Features Desired in a Pharmaceutical Suspensions

1. A properly prepared suspension should settle slowly &

should be readily redispersed upon gentle shaking of

the container.

2. The characteristics of the suspension should be such

that the particles size of the suspensoid remains fairly

constant throughout long periods of undisturbed

standing.

3. The suspension should pour readily & evenly from its

container

- Good pharmaceutical suspensions, the

particle diameter is between 1 to 50.

- Particle size reduction is generally

accomplished by dry-milling prior to the

incorporation of the dispersed phase into the

dispersion medium.

- One of the methods of producing fine drug

powders of about 10 to 50 um size is

micropulverization.

- For still finer particles, under 10 um, the

process of fluid energy grinding, sometimes

referred to as jet-milling or micronizing.

Dispersion Medium

Suspending agents are added to the dispersion

medium to lend its structure to assist in the suspension of

the dispersed phase

Examples:

- Carboxymethylcelulose

- Methylcellulose

- Microcrystalline cellulose

- Polyvinyl pyrolidone

- Xanthan gum

- Bentonite

The amount of the suspending agent must not be such

to render the suspension too viscous to agitate (to

distribute the suspensoid) or to pour. The study of the

flow characteristics is termed rheology.

Sustained-Release Suspension

In liquid preparations (suspensions) of the coated

particles, the drug remains adsorbed onto resin, but

slowly released by the ion-exchange process when

taken into gastrointestinal tract. The use of a

combination of ion-exchange resins complex and

particle coating is called Pennkinetic system.

Examples:

- Hydrocodone polistirex =Tussionex

- Pennkinetic Extended-Release Suspension

Packaging and Storage of Suspensions

All suspensions should be packaged in containers

having:

1. Adequate airspace above the liquid to permit

adequate shaking.

2. Should be provided in wide mouth containers to

permit the prompt and ease of removal of the

suspension.

3. Store in tight containers protected from freezing,

excessive heat and light.

4. Suspensions should be shaken before use.

GeLoMaMi

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Example of preparation:

Aluminum Hydroxide Compressed

Gel 326.8 g

Sorbitol Solution 282.0 mL

Syrup 93.0 mL

Glycerin 25.0 m

Methylparaben 0.9 g

Propylparaben 0.3 g

Flavor q.s

Purified water, to make 1000.0 mL

USE: ANTACID

Preparation…

methylparaben & propylparaben - preservatives; syrup

and sorbitol - viscosity and sweetness.

In the preparation, the parabens are dissolved in a

heated mixture of the sorbitol solution, glycerin, syrup

and a portion of the water. The mixture then cooled

and the aluminum hydroxide added with stirring. The

flavor is added and sufficient purified water to

volume. The suspension is then homogenized, using

hand homogenizer, homomixer, or colloid mill

Examples of Oral Suspensions by Category

Antacids Alumina, Magnesia and Simethicone - Mylanta

liquid

Magaldrate Oral Suspension - Riopan Oral

Suspension

Magnesia and Alumina Oral - Maalox

Suspension

Aluminum Hydroxide and Magnesium

Carbonate - Gaviscon liquid

Anthelminitics Pyrantel Pamoate - Antiminth Oral Suspension

Thiabenzadole Oral Suspension - Mintezol Oral

Suspension

Antibacterial

(Antibiotics)

Chloramphenicol Palmitate - Chloromycetin

Palmitae Oral Suspen.

Ertythromycin Estolate - Ilosone Oral Suspension

Antibacterial

(non-antibiotic

Anti-infectives)

Methenamine Mandelate - Mandelamine

Suspension/Forte

Sulfamethoxazole and Trimethoprim - Bactrim,

Septra Susp.

Sulfamethoxazole - Gantanol Suspension

Sulfisoxazole Acetyl Oral Suspension- Gantrisin

Syrup/Pedia

Anticonvulsants Pimidone Oral Suspension - Mysoline

Suspension

Antidiarrheal Bismuth Subsalicylate - Pepto-Bismol liquid

Antiflatulent Simethicone Oral Suspension - Mylicone Drop

Antifungals Nystatin Oral Suspension - Nystatin Oral Susp

Griseofulvin Oral Suspension -Grifulvin Oral Susp

Antihypertensive Methyldopa Oral Suspension - Aldomet Oral

Suspension

Antipsychotics,

Sedatives,

Antiemetic

Hydroxyzine Pamoate Oral Suspension - Vistaril

Oral Suspension

Thioridazine Oral Suspension - Mellaril-S Oral

Suspension

Diuretic Chlorothiazide Oral Suspension - Diuril Oral

Suspension

Nonsteroidal

Anti-

inflammatory

Indomethacin Oral Suspension - Indocin Oral

Suspension

Antacid Oral Suspension

Are intended to counteract the effects of gastric

hyperacidity and such are employed by persons, as

peptic ulcer patients, who must reduce the level of

acidity in the stomach. Also referred to as “acid

indigestion”, “heartburn”, and “sour stomach”

Example:

- Sodium Bicarbonate

- Aluminum hydroxide

- Aluminum phosphate

- Dihydroxyaluminum aminoacetate

- Calcium carbonate

- Calcium phosphate

- Magaldrate

- Magnesium carbonate

- Magnesium oxide

- Magnesium hydroxide

Antibacterial Oral Suspension

The antibacterial oral suspensions include preparations

of antibiotic substances

Examples:

- Antibiotics ( Chloramphenicol

palmitate, Erythromycin derivatives,

and tetracycline and its derivatives)

- Sulfonamides (Sulfamethoxazole,

sulfisoxazole acetyl)

- other chemotherapeutic

agents(methanamine mandelate &

nitrofurantoin)

- combination of these

(sulfamethoxazole - trimethoprim)

Otic Suspension

Examples:

- Polymixin B sulfate

- Neomycin sulfate

- Hydrocortisone - pH 3.0 to 3.5

- Cortisporin Otic Suspension - pH 4.8 to 5.1

- PediOtic - pH of 4.1

Note: Pharmacist must be aware that there may be

subtle differences in the formulation of some otic

suspensions that could be potentially bothersome to

the patient

Rectal Suspensions

Examples:

- Barium sulfate for Suspension, USP may be

employed orally or rectally for the diagnostic

visualization of the GIT.

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- Mesalamine (5-aminosalicylic acid) - for

treatment of Crohn’s disease, distal ulcerative

colitis, proctosigmoiditis, and proctitis.

Dry Powders for Oral Suspension

Preparations consist of dry powder mixtures or granules,

which are intended to be suspended in water or some

other vehicle prior to administration.

The dry products contain

1. Antibiotic

2. Colorant (FD and C dyes)

3. Flavorants

4. Sweeteners - sucrose or sodium saccharin

5. Stabilizing agents - citric acid and sodium citrate

6. Suspending agents - guar gum, xanthan gum,

methylcellulose

7. Preserving agents - methylparaben, sodium

benzoate

NOTE: When called on to “RECONSTITUTE” and

dispense, the pharmacist loosens the powder at the

bottom of the container by lightly tapping it against a

hard surface, and then adds label designated amount

of purified water, usually in portions, and shakes well

until all of the powder has been suspended.

Examples of Antibiotics for Oral Suspension (Reconstitution)

Amoxicillin for Oral Suspension AMOXIL FOR ORAL SUSPENSION

Ampicillin for Oral Suspension OMNIPEN FOR ORAL SUSPENSION

Bacampicillin for Oral Suspension

SPECTROBID

FOR ORAL SUSPENSION

Cefaclor for Oral Suspension

CECLOR

FOR ORAL SUSPENSION

Cefixime for Oral Suspension

SUPRAX POWDER

FOR ORAL SUSPENSION

Cephadrine for Oral Suspension

KEFLEX

FOR ORAL SUSPENSION

Dicloxacillin Sodium for Oral Suspension

(PATHOCIL)

FOR ORAL SUSPENSION

Doxycycline for Oral Suspension

VIBRAMYCIN MONOHYDRATE

FOR ORAL SUSPENSION

Erythromycin Ethylsuccinate for Oral

Suspension

E.E.S. GRANULES

FOR ORAL SUSPENSION

Penicillin V for Oral Suspension

Other examples (Combination)

1. Erythromycin ethylsuccinate/acetylsulfisoxazole

granules - treatment for acute middle ear infection -

Hemophilus influenza

2. Probenecid/ampicillin for reconstitution - treatment for

uncomplicated infections (urethral, endocervical or

rectal) - Neisseria gonorrhoeae

EMULSIONS

The word emulsion, came from emulgio, “meaning to

milk out”.

Is a dispersion in which the dispersed phase is

composed of small globules of a liquid distributed

throughout a vehicle in which it is immiscible.

Emulsion terminology

The dispersed phase is referred to as the Internal phase

The dispersion medium as the External or Continuous

phase

Emulsions having an oleaginous internal phase and

aqueous external phase are referred to as oil-in-water

(o/w) emulsions

Emulsions having an aqueous internal phase and an

oleaginous external phase are termed water-in- oil

(w/o) emulsions.

Unless a third component - the emulsifying agent - is

present the dispersion is unstable, and the globules

undergo coalescence to form two separate layers of

water and oil

Because the external phase of an emulsion is

continuous, an O/W emulsion may be diluted with

water or an aqueous preparation, & W/O emulsion with

an oleaginous or oil miscible liquid

The aqueous phase may contain water-soluble drugs,

preservatives, coloring and flavoring agents

The oil phase frequently consists of fixed oil or volatile

and drugs that exist as oil, such as oil-soluble vitamins

and antiseptic

It is necessary to add antioxidant to prevent

autoxidation of the oil and rancidity/and or destruction

of any vitamin present.

Purpose of Emulsification

1. Pharmaceutically

a. The pharmacist can prepare relatively stable

and homogenous mixture of 2 immiscible

liquids

b. Emulsification can permit the administration of

liquid drug in the form of minute globules

rather than in bulk

2. Therapeutically

a. Beneficial to the rate and degree of

absorption of the drug after administration by

any of the usual route

b. O/W emulsions may also be useful as vehicle

to develop the bioavailability of poorly

absorbed drugs

c. For orally administered emulsion the O/W type

permits the palatable administration of an

otherwise distasteful oil by dispersing it in a

sweetened, flavored vehicle.

d. The reduced particle size of the oil globules

may render the oil more digestible and more

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readily absorbed and therefore more

effective

e. Emulsion to be applied externally can be

made such that the medicinal agent that are

irritating to the skin surface may be

incorporated in the internal phase than in the

external phase since the latter is in direct

contact with the skin

f. On the unbroken skin, a W/O emulsion can

usually be applied more evenly since the skin

is covered with a thin film sebum, and this

surface is more readily wetted by oil than by

water. On the other hand, if it is easily

removed from the skin, O/W is preferred.

Theories of Emulsification

1. Surface Tension Theory

- A property of liquids in which the exposed

surface tends to contract to the smallest

possible are. In a spherical drop of liquid there

are internal forces that tend to promote the

association of the molecule of the substance

to resist the distortion of the drop into a less

spherical form

- The use of substances as emulsifiers &

stabilizers

- Results in the lowering of the interfacial tension

of the 2 immiscible liquids, reducing the

repellant force between the liquids and

diminishing each liquids attraction for its own

molecules. These tension lowering substances

are referred to as surface active (surfactants)

or wetting agents.

2. Oriented-Wedge Theory

- Assumes monomolecular layers of emulsifying

agent curved around a droplet of the internal

phase of the emulsion.

- It is based on the presumption that certain

emulsifying agents orient themselves about

and within a liquid in a manner reflective of

their solubility in that particular liquid.

- An emulsifying agent having a greater

hydrophilic character than hydrophobic

character will promote an O/w emulsion and

a W/O emulsion results through use of more

hydrophobic than hydrophilic emulsifiers.

3. Plastic or Internal Film Theory

- Places the emulsifying agent at the interface

between the oil and water, surrounding the

droplets of the internal phase as a thin layer of

film adsorbed on the surface of the drops.

- The film prevents the contact and the

coalescence of the dispersed phase, the

tougher and more pliable the film, the greater

the stability of the emulsion.

4. Viscosity Theory

- States that the viscosity of an emulsion aids

emulsification by the mechanical hindrance

to coalescence of the globules although it is

not the cause of emulsification.

Emulsifying Agents

1. Natural emulsifying agent

- These materials form hydrophilic colloids when

added to water and generally produced

O/W emulsions. Acacia is most frequently use.

Tragacanth and Agar - thickening agents in

Acacia emulsified products.

- These substances produce O/W emulsions.

The disadvantage of gelatin is that the

emulsion prepared from it is too fluid

- Carbohydrates: acacia, tragacanth, agar,

chondrus, pectin

- Proteins: gelatin, egg yolk, casein

2. High Molecular Weight alcohols

- These materials employed primarily as

thickening and stabilizing agents for O/W

emulsions such as lotion and ointments

- Cholesterol may also be employed in

externally used emulsion and promote W/O

emulsions.

- E.g. stearyl alcohol, cetyl alcohol, glyceryl

monostearate

3. Finely divided solids

- These materials generally form O/W emulsions

when the insoluble material is added to the

aqueous phase if there is greater volume of

the aqueous phase than of the oleaginous

phase

- Colloidal clays including: Bentonite,

Magnesium hydroxide, Aluminum hydroxide

4. Synthetic

- (wetting agents), which may be:

a. Anionic: triethanolamine oleate and

sodium lauryl sulfate

b. Cationic: benzalkonium chloride

c. Nonionic: sorbitan esters (span);

polyethylene glycol 400 monostearate;

polyoxyethylene sorbitan esters (Tweens)

Qualities Required for Emulsifiers

Must be compatible with other ingredients in the

formula

Must not interfere with the stability and efficacy of the

therapeutic agent

Must be stable to microorganisms

Must be non-toxic

Must possess little or no odor, taste or color

Must promote emulsification and maintain stability of

the emulsion for intended shelf-life

The HLB or Hydrophilic- Lipophile Balance

Each emulsifying agents has a hydrophilic portion

(water-loving) and a lipophilic portion (oil-loving) with

one or other being more or less predominant and

influencing

A method indicative of the substances polarity devised

and lead to the assigning of an HLB value for each

agent. The usual range is between 1 to 20.

Materials that are highly polar or hydrophilic have

assigned higher numbers than materials that are less

polar and were lipophilic

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Surfactants having an assigned HLB value from 3 to 6

are greatly lipophilic and produce W/O emulsions and

those HLB values of from about 8 to 18 produce O/W

emulsions.

In selecting an Emulsifier for an emulsion, choose one

having the same or nearly the same HLB value as the

oleaginous phase

Ex.: Mineral oil has assigned HLB of 4 if a W/O emulsion

is desired and a value of 10.5 if O/W emulsion is

prepared

Therefore, use surfactant SPAN 80 (Sorbitan monoleate)

with HLB 4.3 for W/O emulsion and methylcellulose with

HLB of 10.5 for O/W.

Examples of HLB Values for Selected Emulsifiers

Ethylene glycol distearate .5

Sorbitan tristearate (Span 65) 2.1

Propylene glycol monostearate 3.4

Triton X-15 3.6

Sorbitan monooleate (Span 80) 4.3

Sorbitan monostearate (Span 60) 4.7

Diethylene glycol monolaurate 6.1

Examples of HLB Values for Selected Emulsifiers

Sorbitan monopalmitate (Span 40) 6.7

Sucrose dioleate 7.1

Acacia 8.0

Amercol L-101 8.0

Polyoxyethylene lauryl ether (Brij 30) 9.7

Gelatin 9.8

Triton X-45 10.4

Methylcellulose 10.5

Polyoxyethylene monostearate (Myrj 45) 11.1

Triethanolamine oleate 12.0

Tragacanth 13.2

Triton X-100 13.5

Polyoxyethylene sorbitan monostearate (Tween 60)

14.9

Polyoxyethylene sorbitan monooleate (Tween 80)

15.0

PSM (Tween 20) 16.7

Pluronic F 68 17.0

Sodium oleate 18.0

Potassium oleate 20.0

Sodium lauryl sulfate 40.0

Activity and HLB Value of Surfactants

Activity Assigned HLB

1. Antifoaming 1 to 3

2. Emulsifiers (W/O) 3 to 6

3. Wetting agents 7 to 9

4. Emulsifiers (O/W) 8 to 18

5. Solubilizers 15 to 20

6. Detergents 13 to 15

Methods of Preparation

1. Continental or Dry gum method

The method is also referred to as the “4:2:1”

method because for every 4 parts (volumes)

of oil, 2 parts of water and 1 part of gum are

added in preparing the initial or primary

emulsion.

For instance, if 40 mL of oil are to be

emulsified, 20 mL of water and 10 g of gum

would be employed, with additional water or

other formulation ingredients being added

afterward to the primary emulsion

a. The acacia or other O/W emulsifier is

triturated with the oil in a perfectly dry

Wedgewood or porcelain mortar until

thoroughly mixed.

b. After the oil and gum have been mixed,

the two parts of water are then added all

at once, and the mixture is triturated

immediately, rapidly, and continuously

until the primary emulsion that forms is

creamy white and produces a crackling

sound to the movement of the pestle

c. Generally, about 3 minutes of mixing are

required to produce such a primary

emulsion

d. . Other liquid formulative ingredients that

are soluble in or miscible with the external

phase may then be added to the

primary emulsion with mixing.

e. 5. Solid substances such as preservatives,

stabilizers, colorants, and any flavoring

material are usually dissolved in a suitable

volume of water and added as a solution

to the primary emulsion

NOTE: A mortar with a rough rather than

smooth inner surface must be used to

ensure proper grinding action and the

reduction of the globule size during the

preparation of the emulsion. A glass

mortar has too smooth a surface to

produce the proper size reduction of the

internal phase.

2. English or wet gum method

3. Bottle or Forbes bottle method (G+O+W)

For the extemporaneous preparation of

emulsions from volatile oils or oleaginous

substances of low viscosities, the bottle

method is used. (2:2:1)

Preparation:

a. The powdered acacia is placed in a dry

bottle

b. Two parts of oil is then added, and the

mixture is thoroughly shaken in the

capped container.

c. A volume of water approximately equal

to the oil is then added in portions

d. The mixture being thoroughly shaken

after each addition

e. When all of the water has been added,

the primary emulsion thus formed may be

diluted to the proper volume with water

or other an aqueous solution of other

formulative agents

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NOTE: This method is not suited for

viscous oils, because they cannot

thoroughly agitated in the bottle.

4. Auxiliary method

An emulsion by either the wet gum or dry gum

methods can generally be increased in

quality by passing it through a hand

homogenizer.

In this apparatus, the pumping action of the

handle forces the emulsion through a very

small orifices which reduces the globules of

the internal phase to about 5 um and

sometime less

5. In SITU soap method

Two types of soap developed by this method

are Calcium soaps and Soft soaps.

Calcium soaps

water - in - oil emulsions which contain

certain vegetable oil (e.g. Oleic acid) in

combination with lime water ( Syn: Calcium

Hydroxide Solution USP) and prepared by

mixing equal volumes of the oil and lime

water

6. Microemulsions

Thermodynamically stable, optically

transparent, isotropic mixtures of a biphasic

oil-water system stabilized with surfactants.

The diameter of droplets in a microemulsion

may be in the range of 100 A (10 microns) to

1000 A whereas in a microemulsion the

droplets may be 5000 angstroms in diameter.

Both O/W and W/O microemulsions may be

formed spontaneously by agitating the oil and

water phases with carefully selected

surfactant.

Advantages:

a. More rapid and efficient oral

absorption of drugs than through

solid dosage forms

b. Enhance transdermal drug delivery

through increased drug diffusion into

the skin

c. The technique potential application

of microemulsion in the

development of artificial red blood

cells and in the argeting of cytotoxic

drugs to cancer cells

Example of Microemulsion

Emulsion Stability

A stable emulsion is characterized by the following:

1. Absence of flocculation and creaming

2. Absence of coalescence of globules & separation of

the layers

3. Absence of deterioration due to microorganisms

4. Maintenance of elegance with respect to

appearance, odor, color and consistency

Emulsion is considered physically unstable if:

The internal or dispersed phase upon standing tends to

form aggregates of globules.

Large globules or aggregates of globules rise to the top

or fall to the bottom of the emulsion to forconcentrated

layer of the internal phase.

If all or part of the liquid of the internal phase becomes

“unemulsified” and forms a distinct layer on the top or

bottom of the emulsion as result of the coalescing of

the globules of the internal phase

Terminology

1. Flocculation - is the joining together of globules to form

large clumps or floccules which rise or settle in the

emulsion more rapidly than do the individual particles

2. Creaming - is the rising (upward creaming) or settling

(downward creaming) of globules or floccules to form

a concentrated layer at the surface or to the bottom of

the emulsion

3. Coalescence & breaking - unlike creaming, the

coalescence of globules and the subsequent breaking

of an emulsion are irreversible processes. In creaming,

the globules are still surrounded by a protective

coating or sheath of emulsifying agent and may

redispersed simply by agitating the product.

4. Detoriation by Microorganism - Molds, yeast and

bacteria may bring about decomposition and

contamination of the emulsion. Preservatives should be

more fungistatics than bacteriostatic

5. Miscellaneous Physical & Chemical Change - Light and

rancidity affect the color and the odor of oils and may

destroy their vitamin content. Freezing and thawing

Example: Calamine Liniment (itchy, dry skin,

sunburn)

Calamine………………………

Zinc Oxide ……………………. 80.0 g

Olive oil …………………………

Calcium Hydroxide Sol’n aa q.s ad 1000.0 mL

1. Turpentine Oil Emulsion

Rectified Turpentine oil 150 mL

Acacia powder 50 g

Purified water, q.s to make 1000 mL

2. Liquid Petrolatum Emulsion - Mineral oil Emulsion;

Liquid Paraffin

Mineral oil………………………………… 500 mL

Acacia …………………………………….. 125 g

Syrup ……………………………………… 100 mL

Vanilla …………………………………….. 40 mg

Alcohol ……………………………………. 60 mL


3. Cod liver Oil Emulsion - laxative with empty stomach

Cod liver oil …………………………….. 500 mL

Acacia ……………………………………… 125 g

Syrup ………………………………………. 100 mL

Methyl salicylate ……………………….. 4 mL


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and high temperature result in the coarseness and

breaking of an emulsion.

6. Imbibition - is taking up of a certain amount of liquid

without a measurable increase by a gel with an

increase volume

7. Swelling - is the taking up of a liquid by a gel with an

increase in volume. Only those liquid that solvate a gel

can cause swelling. The swelling of protein gels is

influenced by pH and the presence of electrolytes

8. Syneresis - is when the interaction between particles of

the dispersed phase becomes so great than on

standing, the dispersing medium is squeezed out in

droplets and the gel shrinks. Syneresis is a form of

instability in aqueous and nonaqueous gels

9. Thixotrophy - is a reversible gel-sol formation with no

change in volume or temperature-a type of non-

Newtonian flow.

10. Xerogel - is formed when the liquid is removed from a

gel and only the framewok remains. Examples: gelatin

sheet, tragacanth ribbons and acacia tears

Classification and Types of Gels

Two general classification

1. Inorganic hydrogels - are usually two phase systems

such as Aluminum Hydroxide Gel and Bentonite

Magma

2. Organic Gels - are usually single phase systems and

may include such as gelling agents as Carbomer and

Tragacanth and those that contain an organic liquid,

such Plastibase.

Second classification Scheme

1. Hydrogels - include ingredients that are dispersible as

colloidals or soluble in water and include organic

hydrogels, natural and sythetic gums and inorganic

hydrogels

Ex.: silica, bentonite, tragacanth, pectin, sodium

alginate, methylcellulose, sodium

carboxymethylcellulose and alumina

2. Organogels - include the hydrocarbons, animal and

vegetable fats, soap base greases and the hydrophilic

organogels.

Ex.: Hydrocarbon - Jelene, or Plastibase

Preparation of Magmas and Gels

1. By freshly precipitating the disperse phase

2. By direct hydration in water

Examples of Gelling Agents

1. Acacia

2. Bentonite

3. Carbocymethylcellulose sodium

4. Colloidal silicon dioxide

5. Gelatin

6. Hydroxyethylcellulose

7. Hydroxypropryl methylcellulose

8. Polyvinyl alcohol

9. Propylene carbonate

10. Alginic acid

- obtained from seaweed, prepared products is

tasteless, odorless, yellowish-white colored

fibrous powder

- used as thickening agent in concentrations of

1 to 5%

- swells in water to about 200 to 300 times its

own weight without dissolving

11. Carbomer

- resins with high molecular weight

allylpentaerythritol-cross-linked acrylic acid-

based polymers modified with C10 to C30alkyl

acrylates

- fluffy white powders with large bulk density

(0.5 and 1% aqueous dispersion)

- Ex.: Carbomers 910,934,934P,940 and 1342

12. Cetostearyl Alcohol

13. Ethylcellulose

14. Guar gum

15. Hydroxypropryl cellulose

16. Magnesium aluminum silicate

17. Methylcellulose

18. Povidone

19. Sodium alginate

20. Sodium starch glycolate

21. Starch

22. TragacanthX

23. Xanthan gum

Other examples:

1. Carboxymethylcellulose - concentrations of 4 to 6% of

medium viscosity can be used to produce gel; glycerin

may be added to prevent drying; incompatible with

alcohol

2. CMC sodium - soluble in water at all temperature

3. Colloidal silicone dioxide - can be used with other

ingredients of similar refractive index to prepare

transparent gels

4. Gelatin - dispersed in hot water and cooled to form

gels

5. Magnesium aluminum silicate (Veegum)

- concentrations of about 105 forms a firm

thixotropic gel

- material is inert and has few incompatibilities

but is less used above pH 3.5

6. Plastibase (Jelene) - mixture of 5% low molecular

weight polyethylene and 95% mineral oil

7. Poloxamer (Pluronic)

- concentrations ranging from 15 to 50% to form

gel

- poloxamers 124 (L-44 grade), 188 (F-68 grade),

237 (F-87 grade), 338 (F-108 grade) and 407

(F-127 grade) types are freely soluble in water

F = refers to flake form

L = refers to liquid form

8. Magnesium aluminum silicate (Veegum)

- concentrations of about 105 forms a firm

thixotropic gel

- material is inert and has few incompatibilities

but is less used above pH 3.5

9. Polyvinyl alcohol (PVA)

- used at concentrations of about 2.5% in the

preparartion of various jellies that dry rapidly

when applied to the skin

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- borax is a good agent that will gel PVA

solutions

- for best result, dispersed PVA in cold water,

followed by hot water. It is less soluble in cold.

10. Povidone

- about 10% in concentrations to prepare gels

- also increase solubility of poorly soluble drugs

11. Sodium alginate

- 10 % to produce gels

- aqueous preparations are most stable at pH 4

to 10; below pH 3, alginic acid is precipitated

12. Tragacanth gum

- used to prepare gels that are most stable at

pH 4 to 8

- must be preserved with 0.1% benzoic acid or

.17% methylparaben and 0.03% propyl

paraben

13. Methylcellulose

- 5% to form gels; dispersed with high shear in

about 1/3 of water

MAGMAS and MILK

Are aqueous suspensions of insoluble, inorganic drugs

and differ from gels mainly in that the suspended

particles are larger. When prepared, they are thick

and viscous, so need of a suspending agent

Preparations

1. By Hydration –

Ex.: Hydration of Magnesium oxide

MgO + H2O Mg(OH)2

2. Chemical Reaction

Milk of Bismuth is made by reacting Bismuth

subnitrate with Nitric acid and Ammonium

carbonate with Ammonium solution and then

mixing the resulting two solutions

2NaOH + MgSO4 Mg(OH)2 + Na2SO4

(direct hydration)

Examples of Magmas and Gels

Bentonite Magma NF suspending agent

Sodium Fluoride &

Phosphoric Acid gel USP dental care prophylactic

Fluocinonide Gel USP

Anti-inflammatory

corticosteroid

Tretinoin Gel USP treatment for acne

Erythromycin and Benzoyl

peroxide Gel

Clindamycin Topical Gel

Hydroquinone Gel Hyperpigmented skin

Salicylic acid gel Keratolytic

Desoximethasone gel

Anti-inflammatory and anti-

pruritic agent

Alumnium phosphate gel

(Amphogel) USP Antacid

Alumnium hydroxide gel USP Antacid

Dihydroxyalumninum

Aminoacetate Magma USP Antacid

Milk of Magnesia

(Magnesia Magma) USP Antacid; laxative

AEROSOLS

Are pressured dosage forms containing one or more

active ingredients which upon actuation emit a fine

dispersion of liquid and/or solid materials in gaseous

medium

The term Pressurized package is commonly used when

referring to the aerosol container or completed

product. Pressure is applied to the aerosol system

through the use of one or more liquefied or gaseous

propellants.

Aerosols used to provide an airborne mist are termed

space sprays.

Ex.: room disinfectants, room deodorizers, and space

insecticides.

Aerosols intended to carry the active ingredient to a

surface are termed Surface sprays or surface coatings.

Ex: dermatologic aerosols, pharmaceutical aerosols, as

personal deodorant sprays, cosmetic hair lacquers and

sprays, perfumes and cologne sprays, shaving lathers,

toothpaste, surface pesticide sprays, paint sprays and

others.

Advantages of the Aerosol Dosage Forms

1. A portion of medication may be easily withdrawn from

the package without contamination or exposure to the

remaining material.

2. Hermetic character, the aerosol container protects

medicinal agents from atmospheric oxygen, moisture

and even from light.

3. Topical medication may be applied in a uniform, thin

layer to the skin, without touching the affected area

thus, reducing irritation.

4. By proper formulation and valve control, the physical

form and the particles size of the emitted product may

be controlled which may contribute to the efficacy of

a drug. Example: the fine controlled mist of an inhalant

aerosol. Through the use of metered valves, dosage

may be controlled.

5. Aerosol application is “clean” process, requiring little or

no “wash-up” by the user.

The Aerosol Principle

As aerosol formulation consists of 2 components:

1. The product concentrate is the active ingredient of the

aerosol combined with the required adjuncts, such as

antioxidants, surface-active agents, and solvents, to

prepare a stable and efficacious product.

2. The propellant when the propellant is a liquefied gas or

a mixture of liquefied gases, it frequently serves the

dual role of propellant and solvent or vehicle for the

product concentrate

Examples of Propellants

1. Carbon dioxide

2. Nitrogen

3. Nitrous oxide

4. Fluorinated Hydrocarbons:

Trichloromonofluoromethane;

Dichlorodifluoromethane;

Dichlorotetrafluoroethane;

Chlorpentafluoroethane;

Monochlorodifluoroethane;

Octafluorocyclobutane

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Aerosol Container and Valve Assembly

The effectiveness of the aerosol depends on:

1. proper combination of formulation,

2. container

3. valve assembly.

The formulation must not chemically interact with the

container or valve components to avoid unstability of

the formulation.

The container and the valve must be capable of

withstanding the pressure required by the product

It must be corrosive resistant

Valve must contribute to the form of the product to be

emitted.

AEROSOL SYSTEMS

SPACE AEROSOLS usually operate at pressures between

30 to 40 psig (pounds per square inch gauge) at 700F

and may contain as much as 85% propellant

SURFACE AEROLSOLS commonly contain 30 to 70%

propellant with pressures between 25 to 55 psig at 700F

FOAM AEROSOLS usually operate between 35 and 55

psig at 700F and may contain only 6 to 10% propellant

TWO PHASE SYSTEM = comprised (1) the liquid phase –

propellant and product concentrate (2) the vapor

phase

THREE PHASE SYSTEM = comprised (1) layer of water

immiscible liquid propellant, (2) layer of highly aqueous

product concentrate, and (3) vapor pressure

COMPRESSED GAS SYSTEM = compressed rather

liquefied, gases may be used to pressure aerosols. The

pressure of the compressed gas contained in the

headspace of the aerosol container forces the product

concentrate up the dip tube and out of the valve

Examples: Nitrogen; carbon dioxide; nitrous oxide

Containers

1. Glass, uncoated or plastic coated

2. Metal, including tinplated steel, aluminum, and stainless

steel

3. Plastics

The selection of containers for an aerosol product is based on

1. Its adaptability to production methods

2. Compatibility with formulation components

3. Ability to sustain the pressure intended for the product

4. The interest in design and aesthetic appeal on the part

of the manufacturer

5. Cost

VALVE ASSEMBLY

The function of the valve assembly is to permit the

expulsion of the contents of the can in the desired

form, at the desired rate, and, in the case of metered

valve, in the proper amount or dose.

The materials used in the manufacture of valves must

be inert and approved by BFAD.

Among the materials used in making valve parts are

plastic, rubber, aluminum, and stainless steel

Metered Dose Inhalers (MDIs)

Ex.: Allupent. Each metered dose is delivered through the

mouthpiece upon actuation of the aerosol unit’s valve

Nitrolingual spray - permits a patient to spray droplets onto or

under the tongue for acute relief of an attack, or prophylaxis, of

angina pectoris due to coronary artery disease. The product

contains 200 doses of nitroglycerin in a propellant mixture of

dichlorofluoromethane and dichlorotetrafluoroethane

Filling Operations

Fluorinated hydrocarbon gases may be liquefied by

cooling below their boiling points or by compressing the gas at

room temperature. These 2 features are utilized in the filling of

aerosol containers with propellant.

Cold Filling

Both the product concentrate and the propellant must

be cooled to temperatures of -300 to -40 0F. This temperature is

necessary to liquefy the propellant gas. The cooling system may

be a mixture of dry ice and acetone.

Pressure Filling

The product concentrate is quantitatively placed in the

aerosol container, the valve assembly is inserted and crimped

into place, and liquefied gas, under pressure, is metered into the

valve stem from a pressure burette.

Parts of Aerosol Valve

1. The actuator is the button which the user presses to

activate the valve assembly for the emission of the

product.

2. The stem supports the actuator and delivers the

formulation in the proper form to the chamber of the

actuat

3. The gasket, placed snugly with the stem, serves to

prevent leakage of the formulation when the valve is in

closed position

4. The spring holds the gasket in place and also is the

mechanism by which the actuator retracts when

pressure is released, thereby returning the valve to the

closed position

5. The mounting cup, which is attached to the aerosol

can or container, serves to hold the valve in place.

6. The housing, located directly below the mounting cup,

serves as the link between the dip tube and the stem

and actuator. With the stem, its orifice helps to

determine the delivery rate and the form in which the

product is emitted.

7. The dip tube, which extends from the housing down

into the product, serves to bring the formulation from

the container to the valve.

Testing the Filled Containers

Container is tested under various environmental conditions

1. Leaks

2. Weakness in the valve assembly or container

3. Proper function s of the valve

4. The valve discharge rate - determine by discharging a

portion of the contents of a previously weighed aerosol

during a given period of time, and calculating, by the

difference in weight, the grams of contents discharged

per unit of time.

5. Particle size distribution of the spray

6. For accuracy and reproducibility of dosage when using

metered valves

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Topical Aerosols

Aerosols packages for topical use on the skin which

include:

- Antiinfectives: Povidone - iodine, Tolnaftate

and Thimerosal

- Adrenocortical steroids: Betamethasone and

Triamcinolone Acetonide

- Local anesthetic: Dibucaine hydrochloride

Vaginal and Rectal Aerosols

Aerosols foams are commercially available containing

estrogenic substances and contraceptives agents.

Ex.: ProctoFoam

- contains pramoxine hydrochloride

- use to relieve inflammatory anorectal

disorder

Examples of Inhalation Aerosols

NASAL PREPARATIONS

aqueous preparations, rendered isotonic to nasal fluids

(approximately equivalent to 0.9% sodium chloride)

buffered to maintain drug stability while approximating

the normal pH range of the nasal fluids (pH 5.5 to 6.5),

and stabilized and preserved as required.

Examples of Some Commercial Nasal Preparations

Afrin Nasal

Spray/ drops Oxymetazole

nasal

decongestant/adrenergic

Beconase AQ

Nasal Spray

Bechlomethasone

diproprionate synthetic corticosteroid

Diapid Nasal

Spray Lopressin

antidiuretic; prevention of

diabetes

Nasalcrom

Spray

Cromolyn

allergic rhinitis

Ocean Mist Isotonic sodium

chloride

restore moisture/relieve

dry

Privine HCl

Solution

Naphazoline HCl

nasal

adrenergic/decongestant

Syntocinon

Spray

Tetrahydrozoline

HCl adrenergic/decongestant

Neo-

Synephrine

Oxymetazoline

HCl

nasal

adrenergic/decongestant

Nasalide

Nasal Solution Flunisolide perennial/seasonal rhinitis

OTIC SOLUTIONS

sometimes referred to as ear or aural preparations.

Preparations frequently used in the ear, with

suspensions or ointments also finding some application.

Usually placed in the ear canal by drops or small

amounts for the removal of excessive cerumen (ear

wax), or treatment of ear infections, inflammation, or

pain.

Examples of Some Commercial Otic Preparations

MUCILAGES

The official mucilages are thick, viscid, adhesive liquids,

produced by dispersing gum in water or by extracting

with water mucilagenous principle from vegetable

substances.

Mucilages are used primarily to aid in suspending

insoluble substances in liquids due to their (1) colloidal

character and (2) viscosity which prevents the

immediate sedimentation

Example of Mucilage

Method: Place acacia in wide mouth graduated bottle

with capacity not exceeding 1000 mL. Wash the drug

with cold water, drain and add sufficient quantity of

purified water in which benzoic acid has been

dissolved to make 1000 mL, Stopper and lay the bottle,

rotate occasionally, and when acacia has been

dissolved, strain the mucilage

Albuterol Inhalation Proventil

inhalation

aerosol

Beta-adrenergic

Beclomethasone

Dipropionate

Beclovent

inhalation

Adrenocortical

beconace steroid

Cromolyn Sodium Intal inhaler

Antiasthmatic,

antiallergy

Ipratropium bromide Atrovent Anticholinergic

Isoetharine Mesylate Bronkometer

Sympathomimetic -

brochial asthma

Metaproterenol sulfate Alupent Sympathomimetic

Salmeterol Xinafoate Serevent

Beta-adrenergic

agonist

Terbutaline sulfate Brethaire

Beta-adrenergic

agonist

Triamcinolone acetonide Azmacort

Corticosteroids for

asthma

Americaine Benzocaine local anesthetic

Auralgan Antipyrine,

Benzocaine

Acute otitis

media

Cerumenex

drops

Triethanolamine Cerumenolytic

agent

Chloromyc

etin

Chloramphenicol Anti-infective

Cortisporin

solution

Polymyxin B sulfate,

neomycin sulfate

antibacterial

Debrox

drops

Carbamide

Peroxide

Ear wax remova

Pediotic Polymyxin B sulfate

neomycin sulfate

- Antibacterial

Metreton Prednisolone

sodium phosphate

Antiinflammatory

Otobiotic

solution

Polymyxin B Sulfate,

hydrocortisone

Antibacterial

Vosol

solution

Acetic acid Antibacterial/An

tifungal

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Uses: Demulcent, suspending agent, excipient in

making pills and troches,and as emulsifying agent for

cod liver oil

Method : Mix 75 mL of purified water with glycerin in a

tared vessel, heat to boiling, discontinue application of

heat, add Tragacanth and the Benzoic acid and

macerate during 24 hours, stirring occasionally. Add

sufficient quantity of purified water to make the

mucilage 100 g, stir actively until uniform consistency

and strain through muslin cloth

Uses: excipient for pills or troches, suspending agent for

insoluble substances for internal mixtures and as

protective agent

INHALANTS

Are drugs or combinations of drugs that by virtue of

their high vapor pressure can be carried by an air

current into the nasal passage where they exert their

effect.

The device in which they are administered is termed an

inhaler.

Examples:

1. Amyl Nitrite Inhalant - treatment of anginal pain

2. Propylhexedrine Inhalant - nasal decongestant

INHALATIONS

Inhalations are drugs or solutions of drugs administered

by the nasal or oral respiratory route.

A widely used instrument capable of producing fine

particles for inhalation therapy is the NEBULIZERS.

When volatile medication is added to the water in the

chamber, the medication is volatilizes and also inhaled

by the patient, HUMIDIFIERS will be used.

The common household VAPORIZER, produces a fine

mist of steam that may be used to humidify a room

will be used also.

ULTRASONIC HUMIDIFIERS are also available.

Ex.:

1. Isoetharine inhalation - bronchial asthma

2. Isoproterenol Inhalation - bronchial asthma

LOTIONS

Also called “WASHES” or meaning “LOTIO” or “LAVARE”

to wash. Lotions are liquid suspension or dispersion

intended for external application to the skin, frequently

containing suspended particles or emulsified liquid

droplets.

Depending therefore, whether they are solid-liquid or

liquid-liquid dispersions, some lotions can also classified

as suspension or emulsion.

Characteristics:

Since the finely powdered substances are insoluble in

the dispersion medium, the use of suspending agents

and dispersion agent is made.

If the substance is immiscible, an emusifying agent is

used. Most commonly, the vehicles of lotions are

aqueous.

CHARACTERISTICS OF GOOD LOTION

Dries quickly and provides a protective film that will not

rub off easily. It should not run off the surface of the

skin.

The particles settle or rise only slowly and solid do not

form a hard cake at the bottom of the vessel.

The lotion should pour freely from the bottle and apply

evenly over the affected area.

Should have an acceptable color and odor.

Must remain physically and chemically stable

Free from contamination during storage

Methods Of Preparation

1. Trituration Ex.: Calamine lotion

2. Chemical Reaction Ex.: White lotion

Types Of Lotion According To Use

1. Medical Lotions

a. Antiseptic and germicidal

b. As cooling and mildly anesthetic for skin irritations

Ex.:Benzyl Benzoate Lotion

Benzyl Benzoate 250 mL; Triethanolamine 5 g; Oleic

acid 20 g; water 750 mL - emulsion type lotion

Use: for scabies

Calamine Lotion, USP

liquefied phenol 10 mL; Calamine lotion 990 mL to make 1000 mL

Uses: anesthetic and antiseptic

Lotio Alba; Lotio Sulfurata

Uses: for acne and antiseptic since it has sulfur

Example:

Calamine Lotion

Calamine 80 g

Zinc Oxide 80 g

Glycerin 20 mL

Bentonite Magma 250 mL

Calcium Hydroxide solution q.s.

to make 1000 mL

Uses: relieves itching and pain of sunburn, insect bites

2. Cosmetics Lotions - are applied to hair, scalp, face and

hands. They are common as sunscreen preparation. Contain

glycerin, perfume and preservatives.

Examples Of Medicated Lotions

1. Ammonium Lactate - Lac-Hydrin- Promotes hydration,

removal of excess keratin dry skin, hyperkeratolytic

conditions

2. Benzoyl Peroxide - Sulfoxyl Lotion - antibacterial

(Propionibacterium acnes)

3. Betamethasone Diproprionate - Diprolene - Anti-

inflammatory

4. Betamethasone Valerate- Betatrex - Anti-inflammatory

5. Calamine Lotion -Topical protectant

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6. Clotrimazole - Lotrimin - dermal infections tinea pedis,

tinea cruris, and tinea corporus

7. indane - Kwell Lotion - Pediculicide; scabicide (twice a

week)

8. Hydrocortisone - Hytone - Adrenocortical steroid and

anti-inflammatory

9. Permethrin Rinse - Nix Crème Rinse - a synthetic

pyrethroid which is active against lice, i.e. pediculosis

10. Selenium Sulfide - Selsun and Selsun Blue - Anti-fungal,

antiseborrheic. Used principally in the treatment of

dandruff and seborrheic dermatitis

11. Urea Lotion - Ureacin 10 Lotion - Promotes hydration

and removal of excess keratin dry skin and

hyperkeratotic conditions.

Calamine Liniment/Lotion. Oily BPC

Calamine 50 g

Wool fat 10 g

Oleic acid 5 mL

Arachic oil 500 mL

Ca(OH)2 solution to make 1000 mL

Triturate the calamine with the wool fat, the arachis oil and oleic

acid, previously melted together. Transfer to a suitable

container, add the Ca(OH)2 solution and shake vigorously.

C 14 Suspensions

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