PHRMACEUTICAL DOSAGE

PREPARATIONS
Lesson IV
 ADVANTAGES OF LDF

• Better for patients who have trouble swallowing

• Faster absorption than solids
• Have more flexibility in achieving the proper dosage of medication
• Palatable
 DISADVANTAGES OF LDF

• Less stable because it has shorter shelf-life than other dosage forms.
• Dosage accuracy is difficult to measure.
• Need special storage condition.
• Easily affected by microorganisms.
• Bulky to carry around.
• Easy to loss by the breakage of the container.
• Measuring device is required.
 SYRUPS

• Simple Syrup • Medicated Syrup

Sugar crystals are dissolved in
boiling water with a ratio of 1:1 or
• Flavored Syrup Flavored syrups with medicinal
substances
2:1
Flavorings are added to simple
syrup
 #1 Fruit Juice
#2 Medicate Syrup
• Submission and checking of the
exercise results (next meeting)
Manufacturing
Laboratory Exercises
#3 Lactated ringer’s solution
#4 Sterile Water for Injection
• Submission and checking of the
exercise results (next meeting)
 EMULSION

A biphasic system consisting of two immiscible liquids, one of which

the dispersed phase is finely and uniformly dispersed as globules
throughout the second phase (the continuous phase). Since emulsions
are thermodynamically unstable system, a thirdagent, the emulsifier
is added to stabilize the system (Agarwat and Kajesh, 2007). By
forming a thin film around the globules of dispersed phase (Javed et
al., 2008).

Either the dispersed phase or the continuous phase may vary in

consistency from that of a mobile liquid to semisolid (Alfred, 2005).
So that pharmaceutical emulsions range from lotions(low viscosity) to
creams (high viscosity).

The particle size of the dispersed phase commonly ranges from 0.1 to
100 um (Agarwal and Rajesh, 2007).
 AQUEOUS PHASE Composition of an Emulsion
OILY PHASE EMULSIFYING AGENT
• CONSISTS OF FIXED,
• CONSIST OF PURIFIED OR VOLATILE OR MINERAL • THE COMPONENT WHICH
DEIONIZED WATER OIL WHICH CONTAINS BINDS TWO IMMISCIBLE
WHICH CONTAINS OIL SOLUBLE VITAMINS LIQUIDS, AND STABILIZE
WATER SOLUBLE DRUG, AND ANTISEPTICS. THE THE EMULSION.
PRESERVATIVES, OIL USED IN THE
COLORING AND FORMULATION SHOULD
FLAVORING AGENTS. BE PREVENTED FROM
AUTO-OXIDATION. FIXED
OIL LIKE: CASTOR OIL,
CODLIVER OIL, ALMOND
OIL, LQUID PARAFFIN,
SHARK OIL, VOLATILE
OIL CONTAINING
TURPENTINE OIL,
SANDAL WOOD
OIL,CINNAMON OIL, ETC.
 PARTICLE SIZE

The particle diameter of the dispersed phase generally extends

from 0.1-100 um.

Micro emulsion globules diameter: 0.1-0.2 um.

 TYPES OF EMULSION

1. OIL IN WATER EMULSION

Consist of mixtures of aqueous PROPERTIES:
phase with various oils and
1. Non-greasy
waxes. The oil droplets are
dispersed throughout the aqueous 2. Easily remove from the skin
phase. surface.
3. externally, they provide
cooling
EXAMPLES: effect and internally, to mask
1. Fats and oils for the
bitter taste of oil.
oral
4. Water solble drugs are more
administration;
quickly released from O/W
2. As vehicles for emulsion.
soluble drugs; 5. O/W emulsion give a positive
3. Vanishing creams conductivity test as water,
4. Mayonnaise the external phase is a good
5. vinaigrette conductor of electricity.
2. WATER IN OIL EMULSION
A system in which the water is dispersed as globules in the oil continuous phase.

CHARACTERISITCS:
1. They have an occlusive effect by hydrating the stratum corneum and inhibiting the
evaporation of eccrine secretions.
2. They are useful for cleansing the skin of oil soluble dirt.
3. They are greasy
4. Not water washable.
5. externally, they prevent evaporation of the moisture from the surface of skin like cold
creams.
6. Oil soluble druga are quickl released from W/O emulsion used in external preparations like
creams.
7. It does not give positive conductivity tests since the oil is the external phase which is a poor
conductor of electricity.
EXAMPLES:
1. Butter
2. Propofol
3. Nivea cream
3. MULTIPLE EMULSION
a double emulsion (or multiple). The structure co-exist in water-in-oil and oil-in-water morphologies. It has three distinct bulk
phases and two oil water interfaces. The presence of these two kinds of interfaces means that two different emulsifying agents
are typically required in order to formulate a double emulsion, one to stabilize the inner droplets (primary emulsion) and the
other will stabilize the outer droplets (secondary emulsion).

Two Main Types Example: Classification:

1. Water-in-oil-in-water (W/O/W) Vancomycin 1. Coarse (>3 micrometer in
diameter)
2. Oil-in-water-in-oil (O/W/O)
2. Fine ( 1-3 micrometer in
diameter)
The oil droplets of a W/O/W 3. Micro-multiple emulsions (<1
emulsion have water droplets micrometer in diameter).
dispersed within them, while the
water droplets of an O/W/O
emulsion contain dispersed oil
droplets.
4. Micro Emulsion
The system which consist of water, oil and surfactant, which constitute a
single optically isotropic and thermodynamically stable liquid solution.

Two Types:
1. O/W
2. W/O
 GENERAL METHODS

An O/W emulsion prepared by dividing the oily phase completely into minute globules
surrounding each globule with an envelope of emulsifying agent and finally suspends the
globules in the aqueous phase.while the W/O emulsion is prepared by dividing the
aqueous phase completely into minute globules surrounding each globule with an
envelope of emulsifying agent and finally suspending the globules in the oily phase.
(Christopher and Dawn, 2008).
 OTHER METHODS OF EMULSION PREPARATION

1. CONTINENTAL OR DRY GUM METHOD ( 4-2-1 method). The 4 parts of oils and 1 part of powdered acacia are triturated in a dry mortar u
ntil thoroughly mixed. 2 parts water are then added all at once and the mixture is triturated rapidly until primary emulsion is formed.
Trituration is continued for at least 3 minutes, until emulsion appear creamy and white mixture. At this point it will emit a cracking sound.
Any flavoring and syrups are added gradually with constant stirring.
2. ENGLISH OR WET GUM METHOD. Acacia is first triturated twice its weight of water until a uniform dispersion is obtained. Small portion of
oil is added with continuous, light, rapid trituration. If mixture becomes too viscous, a small quantity of water is added with constant
stirring. Then add the remaining oil. Add the other ingrdients as in dry gum method.
3. BOTTLE METHOD
This is used to prepare emulsions of volatile oils or oleaginous substance of very low viscosities. It is not suitable for very viscous oils since
they cannot be sufficiently agitated inside the bottle.
This method is a variation of the dry gum method. One part powdered acacia (or other gum) is placed in a dry bottle and four parts oil are
added. The bottle is capped and thoroughly shaken. To this, the required volume of water is added all at once, and the mixture is shaken
thoroughly until the primary emulsion forms.
4. IN SITU SOAP METHOD
No emulsifying agent is used. but “in situ” is formed following a chemical interaction between the components.it is effective in preparations
using olive and lime water emulsion, which is selfemulsifying. Equal parts of lime water and olive oil are added to the bottle and shaken.
5. MEMBRANE EMULSIFICATION METHOD
This is based on the concept of generating droplets “drop by drop” to produce emulsion. Here, a pressure is applied direct to the dispersed
phase which seeps through a porous membrane into the continuous phase and in this way the droplets are formed.
 TESTS FOR IDENTIFICATION OF EMULSION TYPE:

• 1. DILUTION/MISCIBILITY TEST
• It involves the addition of continuous phase e.g. in the case of O/W emulsion; the emulsion
remains stable upon unlimited addition of water but will become unstable upon unlimited addition
of oil, that is, the oil will separate. Vice versa is the case with W/O emulsion (Carter, 2007).
• 2. ELECTRICAL CONDUCTIVITY TESTS
• Water is a good conductor of electricity. Hence, an emulsion with water continuous phase will
readily conduct electricity while that with oil continuous phase will not (Aulton, 1988).
• 3. STAINING TEST/ DYE SOLUBILITY TEST
• A small amount of water soluble dye such as methylene blue is added to the emulsion, note that if
water is the continuous phase (O/W emulsion), dye will dissolve uniformly throughout the system.
If oil is the continuous phase (W/O emulsion), dye will remain as cluster on the surface of the
system (Alfred et al.,)
• 4. COBALT CHLORIDE TEST
• When a filter paper soaked in cobalt chloride solution is added to an emulsion and dried, it turns
from blue to pink, indicating that the emulsion is O/W type.
 TESTS FOR IDENTIFICATION OF EMULSION TYPE:

6. FLUORESCENCE TEST
• If an emulsion on exposure to ultra-violet radiations shows continuous fluorescence
under microscope, then it is W/O type and if it shows spotty fluorescence, then it is O/W
emulsion.
 THEORIES OF EMULSIFICATION

• THEORIES HAVE BEEN DISCOVERED IN AN ATTEMPT TO EXPLAIN HOEW EMULSIFYING AGENTS WORK AND MAINTAIN THE
STABILITY OF THE EMULSION.

1. SURFACE TENSION THEORY

• The use of surfactants as emulsifiers and stabilizers lowers the interfacial tension of the two immiscible liquids, reducing
the repellent force between the liquids and diminishing each liquid attraction for its own molecules. Thus, the surfactants
facilitate the breaking –up of large globules into smaller ones, which then have a lesser tendency to reunite or coalesce.
2. ORIENTED – WEDGE THEORY
• In a system containing two immiscible liquids, presumably the emulsifying agent is preferentially soluble in one of the
phases and is embedded more deeply and tenaciously in that phase than the other. Many molecules of substances upon
which theory is based (soaps) have a hydrophilic head and hydrophobic tail, the molecule position or orient themselves into
each phase. Depending on the shape and size of the molecules, their solubility characteristics, and thus their orientation,
Like for example the wedge shape envisisoned for the molecules causes either oil blobules or water globules to be
surrounded. Generally, an emulsifying agent having a greater hydrophilic than hydrophobic character will promote an O/W
emulsion and a W/O emulsion results from use of an emulsifying agent that is more hydrophobic than hydrophilic.
• In other words, the phase in which emulsifying agent is more soluble will become the continuous phase.
• This theory may not totally represent an accurate depiction of the molecular arrangement of the emulsifier molecules, the
concept that water soluble emulsifiers generally do form O/W emulsion is important and is frequently encountered in
practice.
3. PLASTIC OR INTERFACIAL FILM THEORY
• It places the emulsifying agent at the interface between the oil and water, surrounding
droplets of the internal phase as a thin layer of film adsorbed on the surface of the
drops.the film prevents contact and coalescing of the dispersed phase; the tougher and
more pliable the film, the greater the stability of the emulsion. Naturally enough of the
film forming material must be available to coat the entire surface of each drop of the
internal phase. Here again, the formation of an O/W emulsion depends on the degree of
solubility of the agent in the two phases, with water soluble agents encouraging O/W
emulsion and oil soluble emulsifiers the reverse.
 EMULSIFYING AGENTS

‘’ THE CHEMICAL AGENTS THAT ARE USED TO REDUCE THE COALESCENCE BETWEEN THE
2 IMMISCIBLE LIQUIDS”.

• PROPERTIES:
1. it must be compatible with formulation ingredients
2. Must not interfere with stability and efficacy of the product.
3. Should be non-toxic
4. Should be stable and not deteriorate in the preparation.
5. Should be odourless, colourless and tasteless
6. Should increase the viscosity of the product.
 MECHANISM OF EMULSIFYING AGENTS

• When two immiscible liquids are mixed they form separate layers and the surface free energy of the
system is increased due to interfacial tension, different densities of 2 phases and large surface area of
dispersed phase.
• To stabilize it, emulsifying agent is added, the emulsidying agent first adsorb at the surface of interface
and when interface becomes saturated and no further space remaining, then emulsifying agent moves
toward the bulk of the solution. The emulsifying agent make the two phases miscible in a manner that
the lipophilic portion of it is towards oily phase and hydrophilic towards the aqueous phase. Miscelles
are formed at CMC consisting of 50-150 molecules of emulsifying agent and emeulsification occurs.
• According to the theories, emulsifying agents stabilizes the emulsion by:
• 1. Reducing the surface tension
• 2. Reducing interfacial tension
• 3. Form film around the droplet
• 4. Provides electric potential
 CLASSIFICATION OF EMULSIFYING AGENTS

EMULSIFYING AGENTS

Synthetic and Semi-synthetic Surface Naturally-occurring Materials and

Active Agents Derivatives

1. Anionic surfactants
2. Cationic surfactants 1. Natural polysaccharides
3. Non-ionic surfactants 2. semi-synthetic polysaccharides
4. Amphotheric (lecithin) surfactants
 ANIONIC SURFACTANTS

In aqueous solution these compounds dissociates to form negatively charged anions that are
responsible for there emulsifying ability. They are used in preparations for external application.

• 1. Alkali Metals and Ammonium Soap

• The group consists mainly of the sodium-potassium or ammonium salts of long chain fatty acids such as
sodium stearate.
• They produce stable emulsion but because in acidic conditions these materials will precipitate out as
fatty acids. These materials are most efficient in alkaline medium. This type of emulgent can also be
formed by reacting an alkali such as potassium, sodium or ammonium hydroxide with a fatty acid. The
latter may be a constituernts of a vegetable oil, oleic acid and ammonia for example, are reacted
together to form a soap responsible for stabilizing white liniment . These emulgents are incompatible
with polyvalent cations often causing phase reversal and it is therefore necessary that deionized water is
used in their preparation.
• 2. Soap of Divalent and Trivalent Metals
• Calcium salts are commonly used and often formed in situ during preparation of the product by
interacting the appropriate fatty acid with calcium hydroxide.
• For example, oleic acid is reacted with calcium hydroxide to produce calcium oleate which is emulsifying
agent for both zinc cream BP and some formulations of oily calamine lotion. These emulgents will only
produce W/O emulsions.
3. Amine Soaps

A number of amines form salts with fatty acids. One of the most important of these is based on
triethanolamine and widely used in both pharmaceutical and cosmetic products.
Example, triethanolamine form stable O/W emulsion by its reaction between triethanolamine and
appropriate fatty acid.

4. Sulfated and Sulfonated Compounds

An example of this is sodium lauryl sulfate, widely used to produce O/W emulsion. It is used with
cetostearyl alcohol to produce emulsifying wax which stabilize such preparation as aqueous cream.
Sulfonated compounds are much less widely used as emulgent they are more often used as wetting
agent or for their detergency.
 CATIONIC SURFACTANTS

In aqueous solutions, these materials dissociate to form positively charged cations that provide the emulsifying properties. They are the most important group of cationic emulgent consist of
the quaternary ammonium compounds. Although these compounds are used for their disinfectant and preservative properties, they are also useful O/W emulsifiers. Cationic surfactants are
toxic and they are to be used only for preparation of antiseptic creams where it is also responsible for its antiseptic properties.

Example:
Cetrimide an emulgent, used at a concentration of 0.5% with 5% cetostearyl alcohol for the formulation of Cetrimide Cream.
 NON-IONIC SURFACTANTS

These products range from oilsoluble compounds stabilizing W/O emulsions to water giving O/W products. They have
low toxicity and irritancy, therefore they are used orally and parenterally administered preparations.they also have
greater degree of compatibility than cationic and anionic emulgents.

• Most non-ionic surfactants are based on:

 a fatty acid- the hydrocarbon chain of which provides the hydrophobic moiety.
 an alcohol – provides the hydrophilic part of the molecule.
 by varying the relative proportions of the hydrophilic grouping many different products can be obtained.

• 1. Glycol and Glycerol Esters

• Glyceryl monostearate is a strongly hydrophobic material that produce weak W/O emulsion. The addition of
small amount oof sodium, potassium or triethanolamine salts of suitable fatty acids will produce a self-
emulsifying glyceryl monostearate which is a useful O/W emulsifier. Self-emulsifying is monostearate to
which anionic soaps have been added. This combination is used to stabilize hydrocortisone lotion. Other
examples include glyceryl monooleate, diethylene glycol monostearate and propylene glycol monooleate.
• 2. Sorbitan Esters
• These are produced by the esterification of one or more of the hydroxyl groups of the sorbitan with either
oleic, palmitic or stearic acid.
• This range of surfactants exhibit lipophilic properties and tend to form W/O emulsions.
3. Polysorbates

Polyethylene derivatives of the sorbitan esters gives polysorbates. They are generally used
inconjunction with the corresponding sorbitan ester to form a complex condensed film at the
O/W interface.
Non-ionic oil soluble materials like glyceryl monostearate, cetyl alcohol or propylene glycol
monostearate can be incorporated with polysorbates to produce self emulsifying preparations
example, polawax which contains cetyl alcohol with a polyethylene sorbitan ester.

4. Fatty Alcohol Polyglycol Esters

These sre condensation products of polyethylene glycol and fatty alcohols. Macrogol
cetostearyl ether or cetomacrogol which is polyethylene glycol monocetyl ether, is the most
widely used,which is very useful water soluble O/W emulgent because of its high water
solubilitywhen introduce into the emulsion formulation.

5. Fatty Acid polyglycol Esters

Stearat esters of polyoxyl stearates are the most widely used. polyoxyethylene 40 stearate is a
water soluble material is often used with stearyl alcohol to give oil in water emulsion.

6. Poloxacols
They are polyoxyethylene/ polyoxypropylene copolymers, comprising of a very large group of
compounds. Some are used as emulsifying agent for intravenous emulsions.
7. Higher Fatty Alcohols
The members of this group are the hexadecyl and the octadecyl of the saturated aliphatic
monohydric alcohols which are very useful in emulsifying agents. Part of their effect come
from their ability to increase viscosity thereby reducing creaming, cetstearyl alcohol also form
interfacial film with hydrophilic surface actice agents such as sodium lauryl sulfate, cetrimide
or cetromacrogol 1000 and stabilize O/W emulsion.
 NATURALLY OCCURRING EMULSIFYING AGENT MATERIALS AND DERIVATIVES

• Disadvantages:
 They show considerable batch to batch variation in composition and emulsifying properties
 Many are susceptible to bacterial growth.
For these reasons, they are not recommended in the preparation of products requiring longer half-life.

1. Natural polysaccharides
The most important emulsifying agent in this group is acacia. This group stabilizes O/W emulsion by forming
strong multimolecular film around each oil globule and coalescence is retarded by the presence of a hydrophilic
barrier between the oil and water phases. Its low viscosity creaming will occur readily and therefore a
suspending agent such as tragacanth or sodium alginate can also included.

2. Semi-synthetic polysaccharides
In order to reduce the problems associated with batch to batch variation, they are available in O/W emulgents or
stabilizers. Several grades of methylcellulose and carmellose sodium are available and exert their action in a
similar way to that of acacia.
Methylcellulose 20 for example is used at a concentration of 2% to stabilize liquid paraffin oral emulsion.