“liquid preparations, intended for oral administration, that contain one or more

substances with or without flavoring, sweetening, or coloring agents dissolved in

water or
co solvent-water mixtures.

Oral solutions can contain certain polyols

(e.g., sorbitol, glycerin) to
inhibit crystallization
and
to modify solubility, taste, mouth feel, and other vehicle
properties.

Drugs in solution are more homogeneous and easier to swallow than drugs in solid
form.

Water
is the most commonly used vehicle for drug solutions. The USP recognizes 07 types
of water for the preparation of dosage forms:

a. Purified water USP

is water obtained by distillation, ion exchange, reverse osmosis, or other

suitable treatment. It cannot contain more than 10 parts per million (ppm) of total
solid and
should have a pH between 5 and 7. Purified water is used in prescriptions and finished
manufactured products except parenteral and ophthalmic products.

b. Water for injection USP

Is water obtained by distillation or by reverse osmosis. It conforms

To the standards of purified water but is also free of pyrogen. Water for injection is
used as a solvent for the preparation of parenteral solutions.

c. Sterile water for injection USP

is water for injection that is sterilized and packaged in single dose containers
of type I and II glass. These containers do not exceed a capacity of 1 L. The
limitations for total solids depend on the size of the container.
d. Bacteriostatic water for injection USP
is sterile water for injection that contains one or more suitable antimicrobial
agents. It is also packaged in single- or multiple-dose containers of type I or
II glass. These containers do not exceed the capacity of 30 mL.
e. Sterile water for inhalation USP
 is water that is purified by distillation or by reverse osmosis (i.e., water for
injection) and rendered sterile. It contains no antimicrobial agents, except when
used in humidifiers or similar devices. This type of water should not be used for
parenteral administration or for other sterile dosage forms.

f. Sterile water for irrigation USP

is water for injection that is sterilized and suitably packaged. It contains no
antimicrobial agents or other added substance.

g. Sterile purified water USP

is purified water sterilized and suitably packaged. It contains no antimicrobial agent.
It is not intended for use in parenterals.

(2. Oral drug solution)

is include syrups and elixirs as well as other less widely prescribed classic
(Galenical) formulations, such as aromatic waters, tinctures, fluid extracts, and
spirits.

a. Syrups
are traditionally per oral solutions that contain high concentrations of sucrose or
other sugars. Through common usage, the term syrup has also come to include any
other liquid dosage form prepared in a sweet, viscous vehicle, including per oral
suspensions.

(1) Syrup NF (simple syrup)

is a concentrated or nearly saturated aqueous solution of sugar (85%; 65% w/w).

(2) Syrups have a low solvent capacity for water-soluble drugs

because the Hydrogen bonding between sucrose and water is very strong.
For this reason, it can be difficult or impossible to dissolve a drug in syrup.
Often, the drug is best dissolved in a small quantity of water, and the flavoring
syrup is added.

(3) The sucrose concentration

of syrup plays a crucial role in the control of microbial growth. Dilute sucrose
solutions are excellent media for microorganisms. As the concentration of sucrose
approaches saturation, the syrup becomes self-preserving (i.e., requires no
additional Preservative). However, a saturated solution is undesirable because
temperature fluctuations may cause crystallization.
Syrup NF is a self-preserved solution with a minimal tendency to undergo
crystallization.

b. Elixirs

Per oral solutions that contain alcohol as a co solvent. Many per oral solutions are
not described as elixirs but contain alcohol.

(1) To be considered an elixir, the solution must contain alcohol. Traditionally, the
alcohol content of elixirs has varied from 5% to 40%.
a) Most elixirs become turbid when moderately diluted by aqueous liquids.
b) Elixirs are not the preferred vehicle for salts because alcohol accentuates saline
taste.
c) Salts also have limited solubility in alcohol. Therefore, the alcoholic content of
salt-containing elixirs must be low.

(2) Aromatic elixir NF,

Prepared in part from syrup, contains approximately 22% alcohol.
The limited usefulness of this elixir as a solvent for drugs was offset by the
development of iso-alcoholic elixir.

It is a combination of low-alcoholic elixir (8% to 10% alcohol), and high-alcoholic

elixir, (73% to 78% alcohol). Mixing appropriate volumes of the two elixirs provides
an alcoholic content sufficient to dissolve the drugs.

B. Miscellaneous solutions
1. Aromatic waters are clear, saturated aqueous solutions of volatile oils or other
aromatic or volatile substances.

a) Aromatic waters may be used as pleasantly flavored vehicles for a water-

soluble drug or as an aqueous phase in an emulsion or suspension. If a large
amount of water-soluble drug is added to aromatic water, then an insoluble layer
may form at the top. This “salting out” is a competitive process.
b) The molecules of water-soluble drugs have more attraction for the solvent
molecules of water than the “oil” molecules. The associated water molecules are
pulled away from the oil molecules, which are no longer held in solution.
c) Aromatic waters should be stored in tight, light-resistant bottles to reduce
volatilization and degradation from sunlight. Aromatic waters are usually
prepared by one of the following methods:
 a. Distillation is a universal method but is not practical or economical for most
products. It is the only method, however, for preparing strong rose water and
orange flower water.

b. With the solution method, the volatile or aromatic substance is admixed with
water, with or without the use of a dispersant (e.g., talc).

2. Spirits, or essences,
Are alcoholic or hydro-alcoholic solutions of volatile substances that contain
(50% to 90% alcohol)
This high alcoholic content maintains the water-insoluble volatile oils in solution. If
water is added to a spirit, the oils separate.
Some spirits are medicinal (e.g., aromatic ammonia spirit).
Many spirits (e.g., compound orange spirit, compound cardamom spirit) are used as
flavoring agents.
Spirits should be stored in tight containers to reduce loss by evaporation.

3. Tinctures
are alcoholic or hydro-alcoholic solutions of chemicals or soluble constituents of
vegetable drugs.
Although tinctures vary in drug concentration (50%), those prepared from potent
drugs are usually 10% in strength (i.e., 100 mL of the tincture has the activity of 10
g of the drug).
Tinctures are usually considered stable. The alcohol content of the official tinctures
varies from (17% to 21% for opium tincture USP )and from ( 74% to 80% for
compound benzoin tincture USP).
Most tinctures are prepared by an extraction process of maceration or percolation.
The selection of a solvent, or menstruum, is based on the solubility of the active and
inert constituents of the Crude drugs.
Aging can cause precipitation of the inactive constituents of tinctures.
Glycerin maybe added to the hydro-alcoholic solvent to increase the solubility of the
active constituent and reduce precipitation on storage.
Tinctures must be tightly stoppered and kept from excessive temperatures.
Because many of their constituents undergo a photochemical change when exposed
tolight, tinctures must be stored in light-resistant containers
 4. Fluid extracts
Are liquid extracts of vegetable drugs that contain alcohol as a solvent,
preservative, or both.

a) Fluid extracts are prepared by percolation so that each milliliter contains the
therapeutic constituents of 1 g of the standard drug. Because of their high
drug content, fluid extracts are sometimes referred to as “100%tinctures.”

b) Fluid extracts of potent drugs are usually 10 times as concentrated, or potent,

as the corresponding tincture.
For example, the usual dose of tincture belladonna is 0.6 mL; the equivalent
dose of the more potent fluid extract is 0.06 mL.
Many fluid extracts are considered too potent for self-administration by patients,
so they are almost never prescribed. In addition, many fluid extracts are simply too
bitter.

6. Mouthwashes
are solutions that are used to cleanse the mouth or treat diseases of the oral mucous
membrane. They often contain alcohol or glycerin to aid in dissolving the volatile
ingredients. Mouthwashes are more oft en used cosmetically than therapeutically.

7. Astringents
are locally applied solutions that precipitate protein. They reduce cell permeability
without causing injury. Astringents cause constriction, with wrinkling and
blanching of the skin. Because astringents reduce secretions, they can be used as
antiperspirants.

a. Aluminum acetate and aluminum subacetate solutions

are used as wet dressings in contact dermatitis. The precipitation is minimized by
the addition of boric acid.

b. Calcium hydroxide solution is a mild stringent that is used in lotions as a

reactant and an alkalizer.

8. Antibacterial topical solutions

(e.g., benzalkonium chloride, strong iodine, Povidone–iodine) kill bacteria when
applied to the skin or mucous membrane in the proper strength and under
Appropriate conditions.
 C. Suspensions

1. Lotions, magmas (i.e., suspensions of finely divided material in a small amount of

water), and mixtures are all suspensions that have had official formulas for some time
(e.g., calamine lotion USP, kaolin mixture with pectin NF). Official formulas are
given in the USP/NF.

 Some drugs are packaged in a dry form to circumvent the instability of aqueous
dispersions.

Water is added at the time of dispensing to reconstitute the suspension.

2. Purposes of suspension

a. Sustaining effect. For a sustained-release preparation, a suspension

necessitates drug dissolution before absorption.

b. Stability. Drug degradation in suspension or solid dosage forms occurs much

more slowly than degradation in solution form.

c. Taste. A drug with an unpleasant taste can be converted into an insoluble

form and then prepared as a suspension.

d. Basic solubility. When suitable solvents are not available, the suspension
provides an alternative. For example, only water can be used as a solvent for
ophthalmic preparations because of the possibility of corneal damage.
Ophthalmic suspensions provide an alternative to ophthalmic solutions.

3. Suspending agents
include hydrophilic colloids, clays, and a few other agents. Some are also used as
emulsifying agents.

a. Hydrophilic colloids
(i.e., hydrocolloids) increase the viscosity of water by binding water
molecules, thus limiting their mobility, or fluidity

Viscosity is proportional to the concentration of the hydrocolloid. These

agents support the growth of microorganisms and require a preservative.
They are mostly anionic, with the exception of methyl cellulose (neutral) and
chitosan (cationic). Thus, the anionic hydrocolloids are incompatible with
quaternary antibacterial agents and other positively charged drugs.
 Chitosan is incompatible with negatively charged drugs and excipients .
Most hydrocolloids are insoluble in alcoholic solutions.

(1) Acacia
is usually used as 35% dispersion in water (mucilage). Its viscosity is greatest
between pH 5 and pH 9. Acacia is susceptible to microbial decomposition.

(2) Tragacanth
is usually used as 6% dispersion in water (mucilage). One advantage of
tragacanth over acacia is that less is needed. Also, tragacanth does not contain
the oxidase that is present in acacia. Th is oxidase catalyzes the
decomposition of organic chemicals. The viscosity of tragacanth is greatest at
pH 5.

(3) Methyl cellulose

is a polymer that is nonionic and stable to heat and light. It is available in
several viscosity grades. Because it is soluble in cold water, but not in hot
water, dispersions are prepared by adding methyl cellulose to boiling water
and then cooling the preparation until the material dissolves.

(4) Carboxy methyl cellulose is an anionic material that is soluble in water.

Prolonged exposure to heat causes loss of viscosity.

b. Clays
(e.g., bentonite, Veegum) are silicates that are anionic in aqueous dispersions. They
are strongly hydrated and exhibit thixotropy (the property of forming a gel-like
structure on standing and becoming fl uid on agitation).

(1) The official form of bentonite is the 5% magma.

(2) Veegum is hydrated to a greater degree than bentonite. Thus, it is more viscous
at the same concentration.

b. Other agents
include agar, chondrus (carrageenan), gelatin, pectin, and gelatinized
starch. Their use is limited by their susceptibility to bacterial attack, their
incompatibilities, and their cost. Xanthan gum is used in many modern
suspension formulations because of its cosolvent compatibility, its stability,
and its solution’s high viscosity relative to concentration.

4. Preparation
a. Solids are wetted initially to separate individual particles and coat them with
a layer of dispersion medium. Wetting is accomplished by levigation (i.e.,
addition of a suitable nonsolvent, or levigating agent, to the solid material,
followed by blending to form a paste), using a glass mortar and pestle or an
ointment slab. A surfactant can also be used.

b. Suspending agents are then added as dry powder along with the active
ingredient. For best results, the suspending agent is added in the form of its
aqueous dispersion.

(1) The aqueous dispersion is added to the solid (or the levigated solid) by
geometric dilution.

(2) The preparation is brought to the desired volume by stirring in the appropriate
vehicle.
D. Emulsions

1. Purposes of emulsions

a. Increased drug solubility.

Many drugs have limited aqueous solubility but have maximum solubility in
the oil phase of an emulsion. Drug partitioning from the oil phase to the water
phase can maintain or enhance activity.

b. Increased drug stability. Many drugs are more stable when incorporated into
an emulsion rather than an aqueous solution.
c.
d. Prolonged drug action. Incorporation of a drug into an emulsion can prolong
bioavailability, as with certain intramuscular injection preparations.

e. Improved taste. Drugs with an unpleasant taste are more palatable and thus
more conveniently administered in emulsion form.
f. Improved appearance. Oily materials intended for topical application are more
appealing in an emulsified form.

2. Phases of emulsions. Most emulsions are considered two-phase systems.

a. The liquid droplet is known as the dispersed, internal, or discontinuous

phase. The other liquid is known as the dispersion medium, external phase, or
continuous phase.
b. In pharmaceutical applications, one phase is usually an aqueous solution. The
other phase is usually lipid or oily.

c. The lipids range from vegetable or hydrocarbon oils to semisolid

hydrocarbons and waxes. Emulsions are usually described in terms of water
and oil. Oil is the lipid, or nonaqueous, phase regardless of its composition.

(1) If water is the internal phase, the emulsion is classified as w/o.

(2) If water is the external phase, the emulsion is classified as o/w.

d. The type of emulsion formed is primarily determined by the relative phase

volumes and the emulsifying agent used.

1) For an ideal emulsion, the maximum concentration of internal phase is

74% (i.e., theoretically,an o/w emulsion can be prepared containing _ 74%
oil).

(1) The choice of an emulsifying agent is more important than the relative phase
volumes in determining the final emulsion type. Most agents preferentially
form one type of emulsion or the other if the phase volume permits.

3. Emulsifying agents.
Any compound that lowers the interfacial tension and forms a film at the
interface can potentially function as an emulsifying agent

A) The effectiveness of the emulsifying agent depends on its chemical structure,

concentration, solubility, pH, physical properties, and electrostatic effect.
B) True emulsifying agents (primary agents) can form and stabilize emulsions by
themselves. Stabilizers (auxiliary agents) do not form acceptable emulsions
when used alone, but assist primary agents in stabilizing the product (e.g.,
increase viscosity).

Emulsifying agents are either natural or synthetic.

a. Natural emulsifying agents

1. Acacia forms a good, stable emulsion of low viscosity. It tends to cream easily,
is acidic, and is stable at a pH range of 2 to 10. Like other gums, it is
negatively charged, dehydrates easily, and usually requires a preservative. It
is incompatible with Peruvian balsam, bismuth salts, and carbonates.
 2. Tragacanth forms a stable emulsion that is coarser than acacia emulsion. It
is anionic, is difficult to hydrate, and is used mainly for its effects on
viscosity. Less than 1/10 of the amount used for acacia is needed.

3. Agar is an anionic gum that is primarily used to increase viscosity. Its stability
is affected by heating, dehydration, and destruction of charge. It is also
susceptible to microbial degradation.

4. Pectin is a quasi-emulsifier that is used in the same proportion as tragacanth.

5. Gelatin provides good emulsion stabilization in a concentration of 0.5% to

1.0%. It may be anionic or cationic, depending on its iso-electric point. Type -
A gelatin prepared from an acid-treated precursor, is used in acidic media.
Type - B gelatin, prepared from an alkali-treated precursor, is used in basic
media.

6. Methyl cellulose is nonionic and induces viscosity. It is used as a primary

emulsifier with mineral oil and cod liver oil, and yields an o/w emulsion. It is
usually used in 2% concentration.

7. Carboxy-methyl-cellulose is anionic and is usually used to increase viscosity.

It tolerates alcohol up to 40%, forms a basic solution, and precipitates in the
presence of free acids.

b. Synthetic emulsifying agents

are anionic, cationic, or nonionic. Although these surfactants are amphiphilic

molecules, their lipophilic and hydrophilic regions are seldom inverse equals of
each other:
Some surfactant molecules tend to be predominantly lipophilic, whereas others
are predominantly hydrophilic. T is imbalance is reflected in the hydrophilic–
lipophilic balance

(HLB) scale: The larger the HLB value, the more hydrophilic the molecule.

HLB values for surfactants and their corresponding uses.

(1) Anionic synthetic agents include sulfuric acid esters (e.g., sodium lauryl
sulfate), sulfonic acid derivatives (e.g., dioctyl sodium sulfosuccinate), and soaps.
Soaps are for external use. They have a high pH and are, therefore, sensitive to the
addition of acids and electrolytes.
 (a) Alkali soaps are hydrophilic and form an o/w emulsion.
(b) Metallic soaps are water insoluble and form a w/o emulsion.
(c) Monovalent soaps form an o/w emulsion.
(d) Polyvalent soaps form a w/o emulsion.

(2) Cationic
synthetic agents (e.g., benzalkonium chloride) are used as surface-active agents in
1% concentration. They are incompatible with soaps.

(2) Nonionic synthetic agents are resistant to the addition of acids and
electrolytes.

(a) The Sorbitan esters known as Spans are hydrophobic in nature and form w/o
emulsions. They have low hydrophilic–lipophilic balance values (1–9)

HLB Value Range Surfactant Application

0–3 Antifoaming agents

4–6 Water-in-oil emulsifying agents
7–9 Wetting agents
8–18 Oil-in-water emulsifying agents
13–15 Detergents
10–18 Solubilizing agents

c) The poly sorbates known as Tweens are hydrophilic and tend to form o/w
emulsions. They may form complexes with phenolic compounds. They have
high HLB values (11–20).

4. Preparation.
Various methods are used to prepare emulsions, depending on the type of
emulsifying agent.
a. Classical, acacia-stabilized emulsions are prepared by one of the following four
methods:

(1) Wet gum (English) method. A primary emulsion of fixed oil, water, and
acacia (in a 4:2:1ratio) is prepared as follows:

(a) Two parts of water are added all at once to one part of acacia. Th e mixture is
triturated
until a smooth mucilage is formed.
(b) Oil is added in small increments (1 to 5 mL), with continuous trituration, until the
primary emulsion is formed.
(c) The mixture (an o/w emulsion) is triturated for another 5 mins.
(d) The o/w mixture can then be brought to volume with water and mixed to achieve
homogeneity.

(2) Dry gum (continental) method. A primary emulsion of the fixed oil, water,
and acacia (in a 4:2:1 ratio) is prepared as follows:

(a) Oil is added to the acacia, and the mixture is triturated until the powder is
distributed
uniformly throughout the oil. Water is added all at once, followed by rapid trituration
to form the primary emulsion.
(b) Any remaining water and other ingredients are added to fi nish the product.

(i) Electrolytes in high concentration tend to crack an emulsion. They should be

added last and in as dilute a form as possible.
(ii) Alcoholic solutions tend to dehydrate and precipitate hydrocolloids. They
should be added in as dilute a concentration as possible.

2) Bottle method
a variation of the dry gum method used for volatile oils).

Oil is added to the acacia in a bottle. The ratio of oil, water, and acacia should be
3:2:1 or 2:1:1. The low viscosity of the volatile oil requires a higher proportion of
acacia.

(3) Nascent soap method. Soap is formed by mixing relatively equal volumes of an
oil and an aqueous solution that contains a sufficient amount of alkali. The
soap acts as an emulsifying agent.

(a) This method is used to form an o/w or a w/o emulsion, depending on the soap
formed. For example, olive oil, which contains oleic acid, is mixed with lime water
during the preparation of calamine lotion to calcium oleate, an emulsifying agent.

(b) A 50:50 ratio of oil to water ensures sufficient emulsion, provided that the oil
contains an adequate amount of free fatty acid. Olive oil usually does. Cottonseed
oil, peanut oil, and some other vegetable oils do not.

(c) The addition of an acid destroys the emulsifying soap and causes the emulsion
to separate.

b. Emulsions stabilized by synthetic emulsifying agents are readily prepared by a

two-phase procedure.
 E. Ointments

1. Introduction.
Ointments are semisolid preparations intended for external use. They are
easily spread. Modifying the formulation controls their plastic viscosity.
Ointments are typically used as

a. emollients to make the skin more pliable,

b. protective barriers to prevent harmful substances from coming in contact with
the skin, and
c. vehicles in which to incorporate medication.

2. Ointment bases

a. Oleaginous bases
Are anhydrous and insoluble in water. They cannot absorb or contain water and
are not washable in water.
(1) Petrolatum is a good base for oil-insoluble ingredients. It forms an occlusive
film on the skin, absorbs 5% water under normal conditions, and does not
become rancid. Wax can be incorporated to stiff en the base.

(2) Synthetic esters are used as constituents of oleaginous bases. These esters
include glyceryl monostearate, isopropyl myristate, isopropyl palmitate,
butyl stearate, and butyl palmitate.

Long-chain alcohols (e.g., cetyl alcohol, stearyl alcohol, PEG) can also be
used.

(3) Lanolin derivatives are oft en used in topical and cosmetic preparations.
Examples are lanolin oil and hydrogenated lanolin.

b. Absorption bases

Are anhydrous and water insoluble. Therefore, they are not washable in water,
although they can absorb water. These bases permit water-soluble
medicaments to be included through prior solution and uptake as the internal
phase.
(1) Wool fat (anhydrous lanolin) contains a high percentage of cholesterol as well
as esters and alcohol that contain fatty acids. It absorbs twice its weight in
water and melts between 36°C and 42°C.
(2) Hydrophilic petrolatum
is a white petrolatum combined with 8% beeswax, 3% stearyl alcohol, and 3%
cholesterol. These components are added to a w/o emulsifier. Prepared forms include
Aquaphor, which uses wool alcohol to render white petrolatum emulsifiable.
Aquaphor is superior in its ability to absorb water.

c. Emulsion bases
May be w/o emulsions, which are water insoluble and are not washable in
Water. These emulsions can absorb water because of their aqueous internal phase.
Emulsion bases may also be o/w emulsions, which are water insoluble but washable in
water. They can absorb water in their aqueous external phase.

(1) Hydrous wool fat (lanolin) is a w/o emulsion that contains approximately
25% water. It acts as an emollient and occlusive film on the skin, effectively
preventing epidermal water loss.

2. Cold cream is a w/o emulsion that is prepared by melting white wax,

spermaceti, and expressed almond oil together; adding a hot aqueous solution
of sodium borate; and stirring until the mixture is cool.

(a) The use of mineral oil rather than almond oil makes a more stable cold cream.
However, cold cream prepared with almond oil makes a better emollient base.

(b) This ointment should be freshly prepared.

3. Hydrophilic ointment is an o/w emulsion that uses sodium -lauryl sulfate as

an emulsifying agent. It absorbs 30% to 50% w/w without losing its
consistency. It is readily miscible with water and is removed from the skin
easily.

4. Vanishing cream is an o/w emulsion that contains a large percentage of water

as well as humectants (e.g., glycerin, propylene glycol) that retards moisture
loss. An excess of stearic acid in the formula helps form a thin film when the
water evaporates.

5. Other emulsion bases include Dermovan, a hypoallergenic, greaseless

emulsion base, and Unibase, a nongreasy emulsion base that absorbs
approximately 30% of its weight in water and has a pH close to that of the
skin.
 d. Water-soluble bases
may be anhydrous or may contain some water. They are washable in water and
absorb water to the point of solubility.

(1) PEG ointment is a blend of water-soluble polyethylene glycols that form a

semisolid base. This base can solubilize water-soluble drugs and some water-
insoluble drugs. It is compatible with a wide range of drugs.

a. This base contains 40% PEG 3350 and 60% PEG 400. It is prepared by the
fusion method

b. Only a small amount of liquid (5%) can be incorporated without loss of

viscosity. This base can be made stiffer by increasing the amount of PEG 3350
to 60%.

c. If 6% to 25% of an aqueous solution is to be incorporated, 5 g of the 40 g of

PEG 3350 can be replaced with an equal amount of Stearyl alcohol.

(2) Propylene glycol and propylene glycol–ethanol form a clear gel when mixed
with 2% hydroxypropyl cellulose. This base is a popular dermatologic vehicle.

3. Incorporation of medicinal agents. Medicinal substances may be incorporated

into an ointment base by levigation or by the fusion method. Insoluble
substances should be reduced to the finest possible form and levigated before
incorporation with a small amount of compatible levigating agent or with the
base itself.

a. Levigation.
The substance is incorporated into the ointment by levigation on an ointment
slab.

(1) A stainless-steel spatula with a long, broad, flexible blade should be used. If the
substance may interact with a metal spatula (e.g., when incorporating iodine and
mercuric salts), then a hard rubber spatula can be used.
(2) Insoluble substances should be powdered finely in a mortar and mixed with an
equal quantity of base until a smooth, grit-free mixture is obtained. The rest of the
base is added in increments.
(3) Levigation of powders into a small portion of base is facilitated by the use of a
melted base or a small quantity of compatible levigation aid (e.g., mineral oil,
glycerin).
(4) Water-soluble salts are incorporated by dissolving them in the smallest possible
amount of water and incorporating the aqueous solution directly into a compatible
base.
(a) Usually, organic solvents (e.g., ether, chloroform, alcohol) are not used to
dissolve the drug because the drug may crystallize as the solvent evaporates.

(b) Solvents are used as levigating aids only if the solid will become a fine powder
after the solvent evaporates.

b. Fusion method.

This method is used when the base contains solids that have higher melting
points (e.g., waxes, cetyl alcohol, glyceryl monostearate). Th is method is also
useful for solid medicaments, which are readily soluble in the melted base.

(1) Th e oil phase should be melted separately, starting with materials that have the
highest melting point. All other oil-soluble ingredients are added in decreasing order of
melting point.
(2) Th e ingredients in the water phase are combined and heated separately to a
temperature that is equal to or several degrees above that of the melted oil phase.
(3) Th e two phases are combined. If a w/o system is desired, then the hot aqueous
phase is incorporated into the hot oil phase with agitation. If an o/w system is
preferred, then the
hot oil phase is incorporated into the hot aqueous phase.

4) Volatile materials (e.g., menthol, camphor, iodine, alcohol, perfumes) are added aft
er the melted mixture cools to 40°C or less.