Pharmaceutics 1

Liquid dosage forms

Solutions

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 Solutions
• In pharmaceutical terms, solutions are “liquid
preparations that contain one or more chemical
substances dissolved in a suitable solvent or
mixture of mutually miscible solvents” ( aqueous or
non –aqueous) .
• It may be classified as oral, otic, ophthalmic, or
topical.
• Certain solutions prepared to be sterile and pyrogen
free and intended for parenteral administration are
classified as injections.

2
Solutions can be formulated for different
routes of administration

Orally: Syrups, elixirs, drops

Parenterally : IV , IM , SC

In mouth and throat: Mouth washes, gargles,

throat sprays.

In body cavities: Douches, enemas, ear drops,

nasal sprays.

On body Surfaces: Collodions, lotions.

3
Advantages of SoIutions

(1) Easier to swallow therefore easier for:

children - old age - unconscious people.

(2) More quickly effective than tablets and

capsules.

(3) Homogenous, , the drug will be uniformly

distributed throughout the preparation therefore
give uniform dose compared to suspension or
emulsion which need shaking.

(4) Some drugs can irritate the gastric mucosa if

localized in one area. Irritation is reduced by
administration of a solution of the drug
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Disadvantages of Solutions
(1) Bulky therefore difficult to transport and store.

(2) Unpleasant taste or odours are difficult to mask.

(3) Needs an accurate spoon to measure the dose.

(4) Less stable than solid dosage forms.

major signs of instability:
colour change,
precipitation
microbial growth
chemical gas formation

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Classification of Solutions According to Vehicle

(a) Aqueous solutions

(b) Non-aqueous solutions

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Aqueous Solutions
Aqueous solutions are homogeneous mixtures that are
prepared by dissolving a solid, liquid or gas in an aqueous
medium (vehicle).

Vehicle: This may be water, aromatic water or extracts.

None- Aqueous Solutions

1. alcoholic or hydroalcoholic solutions, e.g. elixirs
and spirits,
2. ethereal solutions, e.g. the Collodions
3. glycerin solutions, e.g. the glycerites,
4. oleaginous solutions e.g. the liniments, medicated oils,
oleo- vitamins, sprays, and toothache drops.

7
 Oral solutions
• their absorption from the gastrointestinal tract into
the systemic circulation may be expected to occur
more rapidly than from suspension or solid dosage
forms of the same medicinal agent.

• Solutes other than the medicinal agent are usually

present in orally administered solutions.

• These additional agents are frequently included to

provide color, flavor, sweetness, or stability.

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• In formulating or compounding a pharmaceutical
solution, the pharmacist must use information on
the solubility and stability of each solute with
regard to the solvent or solvent system.

• Combinations of medicinal or pharmaceutical

agents that will result in chemical and/or physical
interactions affecting the therapeutic quality or
pharmaceutical stability of the product must be
avoided.

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• For many medicinal agents, their solubility in the usual solvents
are stated in the United States Pharmacopeia– National
Formulary (USP–NF) as well as in other reference books.

• A pharmacist can, in certain instances, dissolve greater

quantities of a solute than would otherwise be possible by using
Solubilizing agent or a different chemical salt form of the
medicinal agent, alteration of the pH of a solution, or
substitution in part or in whole of the solvent.

• Example: iodine in water or an aqueous solution of potassium

iodide or sodium iodide as the solvent , much larger amounts of
iodine may be dissolved in the second solvent as the result of
the formation of a water-soluble complex with the iodide salt.

• This reaction is taken advantage of, for example, in Iodine

Topical Solution, USP, prepared to contain about 2% iodine and
2.4% sodium iodide.
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• Many of the organic medicinal agents are either weak acids
or weak bases, and their solubility depends to a large
measure on the pH of the solvent. These drugs react either
with strong acids or strong bases to form water soluble salts.

11
• Pharmaceutical manufacturers have
prepared many acid salts of these organic
bases to enable the preparation of aqueous
solutions , ex (diphenhydramine HCl) ,
Atropine sulfate

• Many basic salts of weak acids have been

prepared
• Phenobarbital sodium
• silver sulfadiazine
• 12
Water and alcohol solubility of weak acids and weak bases and their salts

13
• The rate of solution, that is, the speed at which the
substance dissolves, depends on:

1. the particle size of the substance: the finer the

powder, the greater the surface area, which comes
in contact with the solvent, and the more rapid the
dissolving process.

2. the extent of agitation: the greater the agitation,

the more unsaturated solvent passes over the drug
and the faster the formation of the solution.
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• 3. Temperature: heating a liquid also causes
solution to take place more rapidly by increasing
the frequency which solvent molecules collide with
the surface of the dissolving mixture

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 Selection criteria for solvents
• the selection of the proper solvent for a particular solute:
• solubility, (like dissolves like)
• clarity,
• low toxicity,
• viscosity,
• Compatibility with other formulative ingredients,
• Chemical inertness,
• palatability,
• odor, color,
• economy.
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 SOLVENTS FOR LIQUID
PREPARATIONS
• PURIFIED WATER, USP, H2O
• Fixed oils
• ALCOHOL, USP
• DILUTED ALCOHOL, NF
• RUBBING ALCOHOL
• GLYCERIN, USP
• PROPYLENE GLYCOL, USP

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 SOLVENTS FOR LIQUID
PREPARATIONS
water
• In most instances, water is the preferred solvent because it
comes closer to meeting these criteria than other solvents.
• Advantages: Tasteless, odourless, lack of pharmacological
activity, neutral and very cheap .
• Disadvantages: favorable medium for some chemical
reactions, and it supports the growth of microorganisms
when contaminated.
• When water is used as the primary solvent, commonly an
auxiliary solvent ( Co-Solvents ) is also employed to
augment the solvent action of water or to contribute to a
product’s chemical or physical stability.
• Alcohol, glycerin, and propylene glycol.
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 PURIFIED WATER, USP, H2O
• Ordinary drinking water from the tap is not
acceptable for the manufacture of most
aqueous pharmaceutical preparations or for
the extemporaneous compounding of
prescriptions

• because of the possible chemical

incompatibilities between dissolved solids
and the medicinal agents being added.

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• Purified Water, USP, is obtained by distillation, ion
exchange treatment, reverse osmosis, or other
suitable process.

• has fewer solid impurities than ordinary drinking

water.
• When evaporated to dryness, it must not yield more
than 0.001% of residue (1 mg of solids per 100 mL of
water).

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• Purified Water, USP intended for use in the
preparation of aqueous dosage forms except those
intended for parenteral administration (injections).

• Water for Injection, USP; Bacteriostatic Water for

Injection, USP; or Sterile pyrogen free Water for
Injection, USP, is used for injections.

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 SOLVENTS FOR LIQUID PREPARATIONS

Fixed oils
• A number of fixed oils, such as corn oil, cottonseed
oil, peanut oil, and sesame oil, are useful solvents,
particularly in the preparation of oleaginous
injections.
Intramuscular injection (IM(
• Rapid absorption from aqueous solution.
• Slow absorption from nonaqueous (oil) solutions.

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 ALCOHOL, USP: ETHYL ALCOHOL,
ETHANOL, C2H5OH
• Next to water, alcohol is the most useful solvent in
pharmacy.
• It is used as a primary solvent for many organic compounds.
• Together with water, it forms a hydroalcoholic mixture that
dissolves both alcohol- soluble and water-soluble
substances.
• Alcohol, USP, is 94.9% to 96.0% C2H5OH by volume (i.e., v/v)
when determined at 15.56°C.
• Dehydrated Alcohol, USP, contains not less than 99.5%
C2H5OH by volume and is used when an essentially water-
free alcohol is desired.

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ALCOHOL, USP

• Certain drugs are insoluble in water and must be

dissolved in an alternative vehicle.

• Alcohol is often preferred because of:

1. its miscibility with water
2. its ability to dissolve many water-insoluble
ingredients, including drug substances, flavorants,
and antimicrobial preservatives.

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ALCOHOL, USP

• Alcohol is frequently used with other solvents, such

as glycols and glycerin, to reduce the amount of
alcohol required.

• It is also used in liquid products as an antimicrobial

preservative alone or with parabens, benzoates,
sorbates.

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 ALCOHOL, USP

• Undesired pharmacological action and potential

toxic effects of alcohol when ingested in
pharmaceutical products, particularly by children.

• Thus, the U.S. Food and Drug Administration (FDA)

has proposed that insofar as possible manufacturers
of over-the-counter(OTC) oral drug products restrict
the use of alcohol and include appropriate warnings
in the labeling.

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ALCOHOL, USP

• For OTC oral products, the recommended alcohol

content limit in product intended for:

• children under 6 years of age, the recommended

alcohol content limit is 0.5%;

• children 6 to 12 years of age, the recommended

limit is 5%;

• children over 12 years of age and adults, the

recommended limit is 10%.

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 DILUTED ALCOHOL, NF
• is prepared by mixing equal volumes of Alcohol, USP,
and Purified Water, USP.

• The final volume of such mixtures is not the sum of

the individual volumes of the two components
because the liquids contract upon mixing; the final
volume is generally about 3% less than what would
otherwise be expected.

• Diluted alcohol is a useful hydroalcoholic solvent in

various pharmaceutical processes and preparations.
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ETHYL ALCOHOL RUBBING ALCOHOL
• contains about 70% ethyl alcohol by volume, the
remainder consisting of water, denaturants with or
without color additives and perfume oils, and
stabilizers.
• must contain sucrose octaacetate or denatonium
benzoate, bitter substances that discourage
accidental or abusive oral ingestion.
• The product is volatile and flammable and should
be stored in a tight container remote from fire.

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RUBBING ALCOHOL

• It is employed as:

1. a rubefacient externally and as a soothing rub for

bedridden patients,
2. a germicide for instruments,

3. a skin cleanser prior to injection.

4. a vehicle for topical preparations.

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 ISOPROPYL RUBBING ALCOHOL
• is about 70% by volume isopropyl alcohol, the
remainder consisting of water with or without color
additives, stabilizers, and perfume oils.

• It is used externally as:

1. a rubefacient
2. soothing rub
3. as a vehicle for topical products.

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 GLYCERIN, USP (GLYCEROL),
CH2OH•CHOH•CH2OH
• Glycerin is a clear syrupy liquid with a sweet taste.
• It is miscible with both water and alcohol.

• As a solvent, it is comparable with alcohol, but

because of its viscosity, solutes are slowly soluble in it
unless it is rendered less viscous by heating.

• Glycerin has preservative qualities and is often used

as a stabilizer and as an auxiliary solvent in
conjunction with water or alcohol.

• It is used in many internal preparations.

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 PROPYLENE GLYCOL, USP,
CH3CH(OH)CH2OH
• a viscous liquid, miscible with water and alcohol.

• It is a useful solvent with a wide range of

applications and is frequently substituted for
glycerin in modern pharmaceutical formulations.

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PREPARATION OF SOLUTIONS

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 Methods of Preparation of Solutions

(a) Simple Solution

(b) Solution by Chemical Reaction
(c) Solution by Extraction

(a) Simple Solution

 Solutions of this type are prepared by dissolving the solute
in a suitable solvent (by stirring or heating).
 The solvent may contain other ingredients which stabilize or
solubilize the active ingredient e.g. solubility of Iodine is 1:
2950 in water however, it dissolves in presence of KI due
the formation of more soluble polyiodides (KI.I2 KI.2I2
KI3.I3 KI.4I4) .[ Strong Iodine Solution USP (Lugol's
SoIution)].
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(b) Solution by Chemical Reaction
These solutions are prepared by reacting two or more
solutes with each other in a suitable solvent e.g. Calcium
carbonate and lactic acid used to prepare Calcium lactate
mixture. WHY?

(c) Solution by Extraction

Plant or animal products are prepared by suitable
extraction process. Preparations of this type may be
classified as solutions but more often, are classified as
extractives.

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 PREPARATION OF SOLUTIONS
• Most pharmaceutical solutions are unsaturated
with solute.

• Thus, the amounts of solute to be dissolved are

usually well below the capacity of the volume of
solvent employed.

• The strengths of pharmaceutical preparations are

usually expressed in terms of percent strength.

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38
Some chemical agents in a given solvent
require an extended time to dissolve. To fasten
dissolution, a pharmacist may employ one of
several techniques, such as:
•Applying heat,
•Reducing the particle size of the solute,
•Using a solubilizing agent,
•Subjecting the ingredients to vigorous
agitation.

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• many medicinal agents are destroyed at elevated temperatures
and the advantage of rapid solution may be completely offset by
drug deterioration.

• If volatile solutes are to be dissolved or if the solvent is volatile

(as is alcohol), the heat would encourage the loss of these agents
to the atmosphere and must therefore be avoided.

• certain chemical agents, particularly calcium salts, undergo

exothermic reactions as they dissolve and give off heat. For such
materials, the use of heat would actually discourage the
formation of a solution.
• A pharmacist may choose to decrease the particle size of the
solute by comminution (grinding a solid to a fine state of
subdivision) with a mortar and pestle on a small scale or
industrial micronizer on a larger scale.
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Stability of solutions
Both physical and chemical stability of solutions in their containers is
very important
A solution must retain its clarity, colour, odour, taste and viscosity
over its shelf life.

The formulation pharmacist must be wary of chemical interactions

between the various components of a solution that may alter the
preparation’s stability and/or potency.

For instance, esters of p-hydroxybenzoic acid (methyl-, ethyl-, propyl-,

and butylparabens), frequently used preservatives in oral
preparations, have a tendency to partition into certain flavoring oils .
This partitioning effect could reduce the effective concentration of the
preservatives in the aqueous medium of a pharmaceutical product
below the level needed for preservative action.

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 DRY MIXTURES FOR SOLUTION
• A number of medicinal agents, particularly certain
antibiotics, e.g., penicillin V, have insufficient stability in
aqueous solution to meet extended shelf-life periods.

• Thus, commercial manufacturers of these products provide

them to the pharmacist in dry powder or granule form for
reconstitution with a prescribed amount of purified water
immediately before dispensing to the patient.

• The dry powder mixture contains all of the formulative

components, including drug, flavorant, colorant, buffers, and
others, except for the solvent.

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• Once reconstituted by the pharmacist, the
solution remains stable when stored in the
refrigerator for the labeled period, usually 7 to
14 days

• This is a sufficient period for the patient to

complete the regimen usually prescribed.

• in case the medication remains after the patient

completes the course of therapy, the patient
should be instructed to discard the remaining
portion, which would be unfit for use at a later
time.

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 ORAL REHYDRATION SOLUTIONS
•Rapid fluid loss associated with diarrhea can
lead to dehydration accompanied by depletion
of sodium, potassium, and bicarbonate ions.
(Na+, K+ & HCO3 -.)

•Replace the lost fluid & electrolytes with an

oral rehydration solution to avoid dehydration.
These are OTC products effective in patients
with mild volume depletion of 5 – 10% of body
weight.
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The active absorption of glucose in the smooth
intestine ( even during diarrhea) promotes:
• glucose absorption is coupled with Na+
absorption
• Na+ promotes anion (X-) absorption,
• NaX absorption promotes H2O absorption.

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To produce maximal absorption of sodium and water,
studies have demonstrated that the optimal
concentrations of glucose and sodium in an
isotonic solution are

1. Glucose: 110 mM ≈ 2% w/v.

2. Na+: 60 mEq/L.
3. Bicarbonate and/or citrate ions are also included in
these solutions to help correct the metabolic
acidosis caused by diarrhea and dehydration.

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• A typical oral rehydration solution contains:
1. 45 mEq Na+,
2. 20 mEq K+,
3. 35 mEq Cl-,
4. 30 mEq citrate,
5. 25 g of dextrose per liter.
• These formulations are available in liquid or powder/
packet form for reconstitution.

• It is important that the user add the specific amount of

water needed to prepare the powder forms.
• these products should not be mixed with or given with other
electrolyte-containing liquids, such as milk or fruit juices.
otherwise there is no method to calculate how much
electrolyte the patient received.
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 SYRUPS
• Syrups are concentrated aqueous
preparations of a sugar or sugar substitute
with or without flavoring agents and
medicinal substances.

• Antihistamine Syrup
• Acetaminophen Syrup
• Cough and Cold Syrup
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 SYRUPS
Syrups containing flavoring agents but not medicinal
substances are called flavored vehicles (non-medicated
syrups) (simple syrup) .

These syrups are intended to serve as:

• Pleasant tasting vehicles for medicinal substances to be
added in the extemporaneous compounding of
prescriptions or in the preparation of a standard formula
for a medicated syrup, which is a syrup containing a
therapeutic agent.

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50
• Syrups provide a pleasant means of administering a
liquid form of a disagreeable-tasting drug.

• They are particularly effective in the administration

of drugs to youngsters, since their pleasant taste
usually dissipates any reluctance on the part of the
child to take the medicine.

• the most frequently found types of medications

administered as medicated syrups are antitussive
agents and antihistamines.

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 COMPONENTS OF SYRUPS
• Most syrups contain the following components in
addition to the purified water and any medicinal
agents present:
• (a) the sugar, usually sucrose, or sugar substitute
used to provide sweetness and viscosity;
• (b) antimicrobial preservatives;
• (c) flavorants;
• (d) colorants.
• Also, many types of syrups contain special
solvents, solubilizing agents, thickeners, or
stabilizers.
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Sucrose- and Nonsucrose-based Syrups
• Sucrose is the sugar most frequently employed in
syrups, although in special circumstances, it may be
replaced in whole or in part by other sugars or
substances such as sorbitol, glycerin, and propylene
glycol.

• In some instances, all glycogenetic substances

(materials converted to glucose in the body)
including materials mentioned above, are replaced
by nonglycogenetic substances, such as
methylcellulose or hydroxyethylcellulose.
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 Methylcellulose or Hydroxyethylcellulose
• Are not hydrolyzed and absorbed into the blood
stream, and their use results in an excellent syrup-
like vehicle for medications intended for use by
diabetic patients and others whose diet must be
controlled and restricted to nonglycogenetic
substances.

• The viscosity resulting from the use of these

cellulose derivatives is much like that of a sucrose
syrup.

• The addition of one or more artificial sweeteners

(aspartame, saccharin) usually produces an
excellent facsimile of a true syrup.
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• The characteristic body that the sucrose and
alternative agents seek to impart to the syrup is
essentially the result of attaining the proper
viscosity.

• This quality, together with the sweetness and

flavorants, results in a type of pharmaceutical
preparation that masks the taste of added
medicinal agents.

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• When the syrup is swallowed, only a portion of the
dissolved drug actually makes contact with the taste
buds, the remainder of the drug being carried past
them and down the throat in the viscous syrup. This
type of physical concealment of the taste is not
possible for a solution of a drug in an unthickened,
mobile aqueous preparation.

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• Most syrups contain a high proportion of sucrose,
usually 60% to 80%, not only because of the desirable
sweetness and viscosity of such solutions but also
because of their inherent stability in contrast to the
unstable character of dilute sucrose solutions.

• The aqueous sugar medium of dilute sucrose

solutions is an efficient nutrient medium for the
growth of microorganisms, particularly yeasts and
molds.

• concentrated sugar solutions are quite resistant to

microbial growth because of the unavailability of the
water required for the growth of microorganisms.
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 simple syrup
• Syrup, NF, also called simple syrup.
• It is prepared by dissolving 85 g of sucrose in
enough purified water to make 100 mL of
syrup (46.3 mL of water )

• The resulting preparation generally requires

no additional preservation if it is to be used
soon; in the official syrup, preservatives are
added if the syrup is to be stored.

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 simple syrup
• Simple syrup contains 85 g sucrose per 100 mL of
solution, which weighs 131.3 g (specific gravity,
131.3 g/100ml ).

specific gravity (s.g. =1.313)

Specific gravity = weight of substance
weigh of equal volume water
1.313 = w , thus, weight of 100 mL syrup is 131.3
100
131.3g - 85g = 46.3 g or mL of water in the syrup.
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• Thus, 46.3 g of water are mixed with 85 g of
sucrose to give syrup 65.5% w/w or 85%w/v.

• It takes 46.3 mL of water to prepare the

solution (131.3 − 85 = 46.3), and the sucrose
occupies a volume of (100 − 46.3 = 53.7) 53.7
mL.
• The solubility of sucrose in water is 1 g in 0.5
mL of water; therefore, to dissolve 85 g of
sucrose, about 42.5 mL of water would be
required.
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• only a very slight excess of water (about 3.8 mL
per 100 mL of syrup) is employed in the
preparation of syrup.

• The slight excess of water permits the syrup to

remain physically stable in varying
temperatures.

• If the syrup were completely saturated with

sucrose, in cool storage, some sucrose might
crystallize from solution
• As formulated, the official syrup is stable and
resistant to crystallization and microbial growth.
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• sucrose-based syrup may be substituted in whole or
in part by other agents in the preparation of
medicated syrups.

A solution of a polyol, such as sorbitol,

or a mixture of polyols, such as sorbitol
and glycerin, is commonly used.

sorbitol

• The polyols, although less sweet than sucrose, have

the advantage of providing favorable viscosity,
reducing cap-locking (which occurs when sucrose
crystallizes), and in some cases acting as
cosolvents and preservatives.

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• Sorbitol Solution, USP, which contains 64% by
weight of the polyhydric alcohol sorbitol, is
employed as shown in the following example
formulations for medicated syrups:

• Antihistamine Syrup
RX
• Chlorpheniramine maleate 0.4 g
• Glycerin 25.0 mL
• Syrup 83.0 mL
• Sorbitol solution 282.0 mL
• Sodium benzoate 1.0 g
• Alcohol 60.0 mL
• Color and flavor q.s.
• Purified water, to make 1000.0 mL
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 Preserving Syrups
• Syrup USP, having a specific gravity of 1.313 and a
concentration of 85% w/v is a 65% w/w solution. This
65% by weight is the minimum amount of sucrose
which will preserve neutral syrup.

• If one wants to formulate a syrup containing less

sucrose, the quantity of alcohol, or other
preservatives, may be estimated.

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• free water is preserved by 18% alcohol

• If other dissolved solids are present, their

volume (often estimated) is subtracted from
the free water volume.

• If glycerin is present, its volume preserves an

equal volume of free water.

• If propylene glycol is present, it is considered

equivalent to ethanol.
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 EXAMPLE

Rx
• Active drug 5 mL volume occupied
• Other drug solids3 ml volume occupied
• Sucrose 25 g
• Glycerin 15 mL
• Ethanol 95% ??.
• Purified water q.s. 100 mL
• How much alcohol would be required to preserve
this prescription?
• Use the free-water method to calculate the quantity
of alcohol required.

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1. Syrup (85 %w/v) has s.g = 1.313, thus,
2. 85 g sucrose are in 100 ml 131.3 g of solution.
3. 131.3g – 85g = 46.3 g or 46.3 mL of water.
4. 100mL - 46.3 mL = 53.7 mL is the v. of 85 g of sucrose.
5. Thus, 85 g of sucrose preserves 46.3 mL of water.

So, 85 g → 46.3 mL
25 g → X, thus, X = 13.62 mL of water preserved.
Volume of sucrose is:
85g → 53.7 mL
25g → x
Thus, X = 15.7 mL
6. v. of active drug + v. of other drugs occupies 5 + 3 = 8 mL
7. 1 mL of glycerin preserves 1 mL of water & occupy 1 mL.
So, glycerin preserves: 15 mL + 15 mL = 30 mL total.
8. The volume taken care = 13.62 + 15.7 + 8 +30 = 67.3 mL.

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9. 100 ml – 67.3 mL of water preserved = 32.68 ml of water
which need preservation.

10. Since it requires about 18% of alcohol to preserve water:

So, 18 → 100 mL
x → 32.68 mL, → x = 5.88 mL of alcohol 100%.

11. But the available alcohol 95%:

So, C1 . V1 = C2 . V2
100 . 5.9 = 95 . V2 → V2 = 6.2 ml of alcohol 95%
is required.
So, add 6.2 ml of alcohol to the syrup and complete volume
up to 100 mL with water.
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• Flavor

• Most syrups are flavored with synthetic

flavorants or with naturally occurring
materials, such as volatile oils (e.g., orange
oil), vanillin, and others, to render the syrup
pleasant tasting. Because syrups are aqueous
preparations, these flavorants must be water
soluble.

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• Colour
• To enhance the appeal of the syrup, a coloring
• agent that correlates with the flavorant
employed (i.e., green with mint, brown with
chocolate,etc.) is used.
• Generally, the colorant is water soluble,
nonreactive with the other syrup components,
and color stable at the pH range and under the
intensity of light that the syrup is likely to
encounter during its shelf life.

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• Antimicrobial Preservatives.

• The amount of preservatives required in a syrup

varies with the proportions of water available for
microbial growth.

• Among the preservatives:

• 1. Benzoic acid-0.1% to 0.2%
• 2. Sodium benzoate – 0.1 to 0.2%
• 3. Combination of methyl, propyl, butyl parabens
totaling 0.1%

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 PREPARATION OF SYRUPS
• methods are:
• (a) solution of the ingredients with the aid of heat,

• (b) solution of the ingredients by agitation without

the use of heat, or the simple admixture of liquid
components,

• (c) addition of sucrose to a prepared medicated liquid

or to a flavored liquid,

• (d) percolation of either the source of the medicating

substance or the sucrose.
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 Solution with the Aid of Heat
Syrups are prepared by this method when:
• It is desired to prepare the syrup as quickly as
possible
• and when the syrup’s components are not damaged or
volatilized by heat.

• In this method:
• The sugar is generally added to the purified water, and
heat is applied until the sugar is dissolved.

• Then, other heat-stable components are added to the

hot syrup,

• The mixture is allowed to cool, And its volume is

adjusted to the proper level by the addition of purified
water.

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• If heat-labile agents or volatile substances,
such as volatile flavoring oils and alcohol, are
to be added, they are generally added to the
syrup after the sugar is dissolved by heat, and
the solution is rapidly cooled to room
temperature.

74
• caution must be exercised against using excessive
heat.

• Sucrose, a disaccharide, may be hydrolyzed into

monosaccharides, dextrose (glucose), and fructose
(levulose).

• This hydrolytic reaction is inversion,

and the combination of the two
monosaccharide products is
invert sugar.

75
• When heat is applied in the preparation of a
sucrose syrup, some inversion of the sucrose is
almost certain.

• The speed of inversion is greatly increased by

the presence of acids, the hydrogen ion acting as
a catalyst to the reaction.

• Should inversion occur, the sweetness of the

syrup is altered because invert sugar is sweeter
than sucrose, and the normally colorless syrup
darkens because of the effect of heat on the
levulose portion of the invert suger.
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• When the syrup is greatly overheated, it
becomes amber colored as the sucrose
caramelizes.

• Syrups so decomposed are more susceptible

to fermentation and to microbial growth
than the stable, undecomposed syrups.

77
 Solution by Agitation Without
the Aid of Heat
• To avoid heat-induced inversion of sucrose,
• On a small scale, sucrose and other formulative
agents may be dissolved in purified water by
placing the ingredients in a vessel larger than
the volume of syrup to be prepared, permitting
thorough agitation of the mixture.

• This process is more time consuming than the

use of heat, but the product has maximum
stability.
78
• other liquids that are soluble in the syrup or miscible
with it may be added and thoroughly mixed.
• When solid agents are to be added to a syrup, it is
best to dissolve them in minimal amount of purified
water and incorporate the resulting solution into the
syrup.

• When solid substances are added directly to a

syrup, they dissolve slowly because:

• the viscous nature of the syrup does not permit the

solid substance to distribute readily throughout the
syrup to the available solvent

• Also a limited amount of available water is present in

the concentrated syrup .
79
 Addition of Sucrose to a Medicated
Liquid or to a Flavored Liquid
• Occasionally a medicated liquid,
such as a tincture or fluidextract,
is employed as the source of medication.
tincture is an alcoholic extract of plant or animal material

• The filtrate is the medicated liquid to which the

sucrose is added in preparation of the syrup.

• It is necessary to take care that medicated

substance should not get precipitated in this
process
80
 Percolation
• In this process, purified water or an aqueous solution is
allowed to pass through a bed of crystalline sucrose.

• A pledget of cotton is put in the neck of the percolator and

purified water or aqueous solution is added in the
percolator containing sucrose.

• The flow rate is controlled by the stopcock

and maintained such that drops appear in rapid
sequence.

• If required, a small portion of liquid is re-passed through

the percolator to dissolve the sugar completely in the
liquid or aqueous solvent.
81
Percolator

82
• either sucrose may be percolated to prepare the
syrup or the source of the medicinal component
may be percolated to form an extractive to
which sucrose or syrup may be added.

• An example of a syrup prepared by percolation

is ipecac syrup, which is prepared by adding
glycerin and syrup to an extractive of powdered
ipecac obtained by percolation.

83
 ELIXIRS
• Elixirs are clear, sweetened hydroalcoholic
solutions intended for oral use and are usually
flavored to enhance their palatability.

• Nonmedicated elixirs are employed as vehicles, and

medicated elixirs are used for the therapeutic effect
of the medicinal substances they contain.

• In addition to alcohol and water, other solvents, such

as glycerin and propylene glycol, are frequently
employed in elixirs as adjunctive solvents.
84
 ELIXIRS
• Phenobarbital Elixir
• Theophylline Elixir

• Medicated elixirs are formulated so that a patient

receives the usual adult dose of the drug in a
convenient measure of elixir. For most elixirs,
one or two teaspoonfuls (5 or 10 mL) provide the
usual adult dose of the drug.

85
 Elixirs Compared with syrups:
• Elixirs are usually less sweet and less viscous
because they contain a lower proportion of
sugar and consequently are less effective than
syrups in masking the taste of medicinal
substances.

• because of their hydroalcoholic character,

elixirs are better able than aqueous syrups to
maintain both water soluble and alcohol-
soluble components in solution.

• Elixirs are more easily prepared ( by simple

solution).
86
• The proportion of alcohol in elixirs varies
widely because the solubility of individual
components of elixir varies widely..

• Each elixir requires a specific blend of

alcohol and water to maintain all of the
components in solution.

• for elixirs containing agents with poor

water solubility, the proportion of alcohol
required is greater than for elixirs
prepared from components having good
water solubility.
87
• elixirs are sweetened with sucrose or with a sucrose
syrup, some use sorbitol, glycerin, and/or artificial
sweeteners.

• Sucrose, which is only slightly soluble in alcohol

usually substituted with an artificial sweetener, such
as saccharin, for sweetening of Elixirs having a high
alcoholic content .

• All elixirs contain flavorings to increase their

palatability, and most elixirs have coloring agents to
enhance their appearance.

• Elixirs containing more than 10% to 12% of alcohol

are usually self-preserving and do not require the
addition of an antimicrobial agent.
88
formulations for some medicated elixirs

• Phenobarbital Elixir
• Phenobarbital 4.0 g
• Orange oil 0.25 mL
• Propylene glycol 100.0 mL
• Alcohol 200.0 mL
• Sorbitol solution 600.0 mL
• Color q.s.
• Purified water, to make 1000.0 mL
89
Advantage / disadvantage of elixirs

• One advantage of elixirs over their counterpart drugs

in solid dosage forms is the flexibility and ease of
dosage administration to patients who have difficulty
swallowing solid forms.

• A disadvantage of elixirs for children and for adults

who choose to avoid alcohol is their alcoholic
content.

• Because of their usual content of volatile oils and

alcohol, elixirs should be stored in tight, light-resistant
containers and protected from excessive heat.

90
 PREPARATION OF ELIXIRS
• Elixirs are usually prepared by simple solution with
agitation and/or by admixture of two or more liquid
ingredients.

• Alcohol-soluble and water-soluble components are

generally dissolved separately in alcohol and in
purified water, respectively.

• Then the aqueous solution is added to the alcoholic

solution, rather than the reverse, so that minimal
separation of the alcohol-soluble components occurs.
91
• When the two solutions are completely mixed, the mixture
is made to the volume with the specified solvent or vehicle.

• Frequently, the final mixture will be cloudy, principally

because of separation of some of the flavoring oils by the
reduced alcoholic concentration.

• If this occurs, the elixir is usually permitted to stand for a

prescribed number of hours to ensure saturation of the
hydroalcoholic solvent and to permit the oil globules to
coalesce so that they may be more easily removed by
filtration.

• Talc, a frequent filter aid in the preparation of elixirs,

absorbs the excessive amounts of oils and therefore assists
in their removal from the solution.

92
 Nonmedicated elixirs
• Nonmedicated elixirs may be useful to the pharmacist in the
extemporaneous filling of prescriptions for example.

• 1) the addition of therapeutic agent to pleasant tasting

vehicle
• 2) dilution of an existing medicated elixir

• When a pharmacist is called on to dilute an existing

medicated elixir, the nonmedicated elixir he or she selects as
the diluent should have approximately the same alcoholic
concentration as the elixir being diluted.

• the flavor and color characteristics of the diluent should not

be in conflict with those of the medicated elixir, and all
components should be chemically and physically compatible.

93
 MEDICATED ELIXIRS
• Most official and commercial elixirs contain a
single therapeutic agent.

• The main advantage of having only a single

therapeutic agent is that the dosage of that
single drug may be increased or decreased by
simply taking more or less of the elixir,

94
 examples of medicated
elixirs.
• Antihistamine Elixirs
• Barbiturate Sedative and Hypnotic Elixirs
• Digoxin Elixir

95
Serum digoxin concentrations following administration of
digoxin 0.5 mg by oral tablet and elixir-like oral solution.
96
97
 TINCTURES
• Tinctures are alcoholic or hydroalcoholic solutions
prepared from vegetable materials or from chemical
substances.
• Tinctures contain alcohol in amounts ranging from
approximately 15% to 80%.

• They vary in method of preparation, strength of the

active ingredient, alcoholic content, and intended
use.

• When they are prepared from chemical substances

(e.g., iodine, thimerosal), tinctures are prepared by
simple solution of the chemical agent in the solvent.

98
• The alcohol content protects against microbial
growth and keeps the alcohol-soluble
extractives in solution.

• In addition to alcohol, other solvents, such as

glycerin, may be employed.

99
 … Tinctures

• Tinctures cannot be mixed successfully with

liquids too diverse in solvent character
because the solute may precipitate.

• For example, compound benzoin tincture,

prepared with alcohol, contains alcohol-
soluble principles that are immediately
precipitated from solution upon addition of
water.

100
• Because of the alcoholic content, tinctures must be
tightly stoppered and not exposed to excessive
temperatures.

• Also, because many of the constituents found in

tinctures undergo a photochemical change upon
exposure to light, many tinctures must be stored in
light-resistant containers and protected from
sunlight.

• Medicated tinctures taken orally are not preferred

by physicians and patients due to their high
alcoholic content.

101
 TOPICAL SOLUTIONS
AND TINCTURES

• The topical solutions employ an aqueous vehicle

• The topical tinctures employ an alcoholic vehicle.

• All medications intended for external use should be

clearly labeled for external use
• As required, cosolvents to enhance solubility or
stability might be employed.
102
• Most topical solutions and tinctures are prepared by simple
solution (dissolving)
• Some are prepared by chemical reaction.
• Because of the nature of the active constituents or the
solvents, many topical solutions and tinctures are self-
preserved. Those that are not may contain suitable
preservatives.
• Topical solutions and tinctures should be packaged in
containers that make them convenient to use.
• Those that are used in small volume, such as the anti-
infectives, are usually packaged in glass or plastic bottles
with an applicator tip as a part of the cap assembly or in
plastic squeeze bottles that deliver the medication in drops.

103
Douches
 Douche is an aqueous solution, which is directed against a part or
into a cavity of the body.
 It functions as a cleansing or antiseptic agent.
 Eye douches are used to remove foreign particles and discharges
from the eyes. It is directed gently at an oblique angle and is
allowed to run from the inner to the outer corner of the eye.
 Pharyngeal douches are used to prepare the interior of the throat
for an operation and to cleanse it in supportive conditions.
 Similarly, there are nasal and vaginal douches.
 Douches most frequently dispensed in the form of a powder with
directions for dissolving in a specified quantity of water.

104
Enemas
 These preparations are rectal injections employed to:
 evacuate the bowel (evacuation enemas ex. Starch enema ),
 influence the general system by absorption (retention
enemas) e.g. nutritive, sedative or stimulating properties
 affect locally the site of disease (e.g. anthelmintic property)
 they may contain radiopaque substances for
roentgenographic examination of the lower bowel.
 Retention enemas are used in small quantities (about 30ml)
and are thus called retention microenema.

105
 TOPICAL ORAL (DENTAL)
SOLUTIONS
• Mouthwash/Gargle:
• Mouthwashes can be used for therapeutic & cosmetic purposes
– Therapeutic mouthwashes can be formulated to reduce
plaque, gingivitis, dental caries and stomatitis.
– Cosmetic mouthwashes may be formulated to reduce bad
breath through the use of antimicrobial and/or flavoring
agents.

– Many gargles must be diluted with water prior to use.

106
 AROMATIC WATERS

• Aromatic waters are clear, aqueous solutions

saturated with volatile oils or other aromatic or
volatile substances.

• Aromatic waters are no longer in widespread use.

• Aromatic waters were prepared from a number of

volatile substances, including orange flower oil,
peppermint oil, rose oil, anise oil, spearmint oil,
wintergreen oil, camphor, and chloroform.

107
• Most of the aromatic substances in the
preparation of aromatic waters have very low
solubility in water, and even though the
water may be saturated, its concentration of
aromatic material is still rather small.

• Aromatic waters may be used for perfuming

and/or flavoring.

108
 SPIRITS
• Spirits are alcoholic or hydroalcoholic
solutions of volatile substances.

• Generally, the alcoholic concentration of spirits

is rather high, usually over 60%.

• Because of the greater solubility of aromatic or

volatile substances in alcohol than in water,
spirits can contain a greater concentration of
these materials than the corresponding
aromatic waters.
109
• When mixed with water or with an aqueous
preparation, the volatile substances present
in spirits generally separate from the
solution and form a milky preparation.

• Spirits may be used pharmaceutically as

flavoring agents and medicinally
for the therapeutic value of the
aromatic solute.

110
• When taken orally, they are generally mixed
with a portion of water to reduce the pungency
of the spirit.

• Depending on the materials, spirits may be

prepared by simple solution, solution by
maceration, or distillation.

• The spirits most recently official in the USP–NF

are aromatic ammonia spirit, camphor spirit,
compound orange spirit, and peppermint spirit.
111
 COLLODIONS

• Collodions are liquid preparations composed

of pyroxylin dissolved in a solvent mixture
usually composed of alcohol and ether with or without
added medicinal substances.

• Pyroxylin (i.e., nitrocellulose,) consists chiefly of

cellulose tetranitrate.

• When applied to the skin with brush or glass

applicator, the solvent rapidly evaporates, leaving a
filmy residue of pyroxylin.

112
• when the collodion is medicated, it
leaves a thin layer of that medication
firmly placed against the skin.

• Collodions must be applied to dry

tissues to adhere to the skin’s surface.

• Collodions are intended for external

use.
• The products must be clearly labeled
“for external use only”

• collodions, are flammable and must

be stored away from flame in well-
closed containers, protected from
light.

113
• Salicylic Acid Collodion
• 10% solution of salicylic acid in flexible collodion.

• It is used for its keratolytic effects, especially in the removal of

corns from the toes.

• Flexible collodion is prepared by adding 2% camphor and 3%

castor oil to collodion. The castor oil renders the product
flexible, permitting its comfortable use over skin areas that are
normally moved, such as joints, fingers, and toes.
• The camphor makes the product waterproof.

114
 GLYCERITES:

• Solutions of mixtures of medicinal or pharmaceutical

substances in glycerin

• Generally a minimum of 50% of glycerin is present in

glycerites

• Glycerites are generally quite viscous with some of them

reaching a jelly like consistency

• Glycerites are considered to be stable preparation and are

not usually as prone to microbial contamination because it
possesses preservative properties

115
• Glycerin alone is used as an otic solution , aid in the
removal of cerumen. Or as solvent for the
preparation of Benzocaine Otic Solution USP.

• Starch Glycerite
• used as an emollient;
• Starch 100g;
• water 200mL;
• Benzoic acid 2g;
• Glycerin 700mL

116