12.

Solutions
 Contents
1. Solubility
2. Some Solvents for Liquid Prep
arations
3. Preparation of Solutions
4. Oral Solutions and Preparatio
ns for Oral Solution
5. Syrups
6. Elixirs
7. Tinctures
8. Proper Administration and Use
of Liquid Peroral Dosage Forms
9. Topical Solutions and Tinctures
10. Vaginal and Rectal Solutions
11. Topical Tinctures
12. Topical Oral (Dental) Solution
s
13. Miscellaneous Solutions
14. Nonaqueous Solutions
15. Extraction Methods for Prepar
ing Solutions
 In pharmaceutical terms, solutions
are “liquid preparations that contai
n one or more chemical substances
dissolved in a suitable solvent or mi
xture of mutually miscible solvents”.
 Because of a particular pharmaceut
ical solution’s use, it may be classifi
ed as
- oral solution,
- otic solution,
- ophthalmic solution,
- topical solution.
 Solutions, because of their compos
ition or use, may be classified as ot
her pharmaceutical dosage forms.
 Syrups
 Elixirs
 Spirits
 Tinctures
Certain solutions prepared to be st
erile and pyrogen-free and intende
d for parenteral administration ar
e classified as injections.
 Oral solutions, syrups, elixirs,
spirits, and tinctures are
prepared and used for the
specific effects of the medicinal
agents they carry.

 In these preparations, the

medicinal agents are intended to
provide systemic effects.
 1. Solubility

 When molecules interact, attractive

and repulsive forces are in effect.

 When the attractive and repulsive

forces are equal, the potential
energy between two molecules is
minimum and the system is most
stable.
 When a solute dissolves, the
substance’s intermolecular forces
of attraction must be overcome
by forces of attraction between
the solute and solvent molecules.

 This entails breaking the solute-

solute forces and the solvent-
solvent forces to achieve the
solute-solvent attraction.
 The solubility of an agent in a
particular solvent indicates the
maximum concentration to which
a solution may be prepared with
that agent and that solvent.

 When a solvent at a given

temperature has dissolved all of
the solute it can, it is said to be
saturated.
Through selection of
 a different solubilizing agent or

 a different chemical salt form of t

he medicinal agent,
 alteration of the pH of a solution,

 or substitution in part or in whole

of the solvent,
a pharmacist can in certain instan
ces dissolve greater quantities of
a solute than would otherwise be
possible.
 Temperature is an important factor
in determining the solubility of a
drug and in preparing its solution.
 Most chemicals absorb heat when
they are dissolved and are said to
have a positive heat of solution,
resulting in increased solubility
with a rise in temperature.
 A few chemicals have a negative
heat of solution and exhibit a
decrease in solubility with a rise in
temperature.
Other factors including
 the various chemical and other

physical properties of both the

solute and the solvent, pressure,
 the pH of the solution,

 the state of subdivision of the

solute,
 and the physical agitation applied

to the solution as it dissolves

affect solubility.
 The solubility of a substance in a
given solvent may be determined

 by preparing a saturated solution

of it at a specific temperature,

 and determining by chemical

analysis the amount of chemical
dissolved in a given weight of
solution.
 The solubility may be expressed as
grams of solute dissolving in
milliliters of solvent.

 When the exact solubility has not

been determined, general expressions
of relative solubility may be used.

 These terms are defined in the USP

and presented in Table 12.1
 A great many of the important organic m
edicinal agents are either weak acids or
weak bases, and their solubility depends
to a large measure on the pH of the solve
nt.

 These drugs react either with strong acid

s or strong bases to form water-soluble s
alts.

 Table 12.2 presents the comparative solu

bilities of some typical examples of weak
acids and weak bases and their salts.
 Commonly, salts of organic
compounds are more soluble in
water than are the corresponding
organic bases.

 Conversely, the organic bases are

more soluble in organic solvents
than the corresponding salt
forms.
 In most instances, especially for s
olutions to be taken orally, used o
phthalmically, or injected, water i
s the preferred solvent.

 When water is used as the primary

solvent, commonly an auxiliary sol
vent is also employed to augment
the solvent action of water or to c
ontribute to a product’s chemical
or physical stability.
 Alcohol, glycerin, and propylene glycol,
have been quite effective in
contributing to the desired
characteristics of pharmaceutical
solutions and in maintaining their
stability.

 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, and are recognized in the
official compendia for this purpose.
2. Some Solvents for Liquid Preparations

(1) Alcohol, USP: Ethyl Alcohol,

Ethanol
(2) Diluted Alcohol, NF
(3) Alcohol, Rubbing
(4) Glycerin, USP (Glycerol)
(5) Isopropyl Rubbing Alcohol
(6) Propylene Glycol, USP
(7) Purified Water, USP
(1) Alcohol, USP: Ethyl Alcohol, Ethanol

 Alcohol is the most useful solvent in p

harmacy next to water. USP, is 94.9 t
o 96% C2H5OH by volume (i.e., v/v)

 Together with water it forms a hydroa

lcoholic mixture that dissolves both al
cohol-soluble and water-soluble subst
ances, a feature especially useful in th
e extraction of active constituents fro
m crude drugs.
 Alcohol has been well recognized as a
solvent and excipient in the formulati
on of oral pharmaceutical products.

 Certain drugs are insoluble in water

and must be dissolved in an alternati
ve vehicle.

 Alcohol is frequently used with other

solvents, such as glycols and glycerin,
to reduce the amount of alcohol req
uired.
  It also is used in liquid products a
s an antimicrobial preservative alo
ne or with parabens, benzoates, so
rbates, and other agents.
 However, concern has been expres
sed over the undesired pharmacol
ogic and potential toxic effects of
alcohol. OTC

hildren under 6 years of age alcohol limit 0.5%

6-12 years of age 5%
Over 12 years of age and adults 10%
 (2) Diluted Alcohol, NF
 Diluted Alcohol, NF, is prepared by
mixing equal volumes of Alcohol, U
SP, and Purified Water, USP.
 The strength of Diluted Alcohol, N
F, is not exactly half that of the mo
re concentrated alcohol but slightl
y greater, approximately 49%.
 Diluted alcohol is a useful hydroalc
oholic solvent in various pharmace
utical processes and preparations.
 (3) Alcohol, Rubbing
 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.
100 denatura
ml nts
Sucrose octaacetate
8 parts acetone
( 蔗糖八乙酸酯） 355 mg
1.5 parts methyl isobutyl keto
or (denatonium benzoate
100 parts ethyl alcohol
地那铵苯甲酸盐 1.4 mg)
 It is employed as a rubefacient ex
ternally and as a soothing rub for
bedridden patients, a germicide f
or instruments, and a skin cleans
er prior to injection.
 It also used as a vehicle for topic
al preparations.
 The product is volatile and flamm
able and should be stored in tigh
t containers remote from fire.
 (4) Glycerin, USP (Glycerol)

 Glycerin is a clear syrupy liquid with a

sweet taste. It is miscible with both
water and alcohol.
 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.
 (5) Isopropyl Rubbing Alcohol
 Isopropyl rubbing alco
hol is about 70% by vol
ume isopropyl alcohol,
the remainder consisti Commercially
ng of water with or wit 91% isopropyl alcohol
hout color additives, st solution
abilizers, and perfume for diabetic patients
disinfecting needles,
oils.
syringes and skin
 It is used externally as
a rubefacient and soot
hing rub and as a vehic
le for topical products.
 (6) Propylene Glycol, USP

 Propylene glycol, a viscous liquid,

is 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.
 (7) Purified Water, USP

 Purified Water, USP, is obtained

by distillation, ion exchange
treatment, reverse osmosis, or
other suitable process.

 It is prepared from water

complying with the federal
Environmental Protection Agency
with respect to drinking water.
Compared with ordinary drinking wate
r,
 Purified Water, USP is more free of s
olid impurities.
 When evaporated to dryness, it must
not yield greater than 0.001% of resi
due (1 mg of total solids per 100 mL
of sample evaporated).
 Purified Water, USP is intended for u
se in the preparation of aqueous dos
age forms, except those intended for
parenteral administration (injetions).
 Distillation Method
 The first portion of aqueous
distillate (about the first 10 to 20%)
must be discarded.

 The last portion of water (about

10% of the original volume of water
) remaining in the distillation
apparatus must be discarded and
not subjected to further distillation.
 Ion-exchange method
 On a large or small scale, the ion-
exchange method for the preparation
of purified water offers a number of
advantages over the distillation
method.

 The ion-exchange process permits

ease of operation, minimal
maintenance, and a more mobile
facility.
 There are mainly two types of resins
in column ion-exchange
- the cation, or acid exchangers, whic
h permit the exchange of the cation
s in solution with hydrogen ion from
the resin
- the anion, or base exchange resins,
which permit the removal of anions.
- These two processes are successivel
y or simultaneously employed to re
move both cations and anions from
water.
 Cation exchange
H-Resin + M+ + X- + H2O M-Res
in + H+ + X- + H2O (pure)

 Anion exchange
Resin-NH2 + H+ + X- + H2O
Resin-NH2HX + H2O (pure)

Water purified in this manner is refe

rred to as demineralized or de-ionize
d water.
 Reverse osmosis
 In this process, a pressurized stream of
water is passed parallel to the inner sid
e of a filter membrane core.
 A portion of the feed water permeates t
he membrane as filtrate.
 The water that has passed through the
system is referred to as the concentrate.
 The flow in this crossflow system is fro
m a more concentrated to a less concen
trated solution-thus the term reverse o
smosis.
 Cross-flow filter membranes can rem
ove particles defined in the range of
 microfiltration (0.1 to 2 microns, e.
g., bacteria)
 ultrafiltration (0.01 to 0.1 microns,
e.g., virus)
 nanofiltration (0.001 to 0.01 micron
s, e.g., organic compounds in the mo
lecular weight range of 300 to 1000)
 reverse osmosis (particles smaller th
an 0.001 microns)
Reverse osmosis removes virtually
all
 virus

 bacteria

 pyrogens

 organic molecules

 and 9099% of all ions.

 3. 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,
expressions of ratio strength may
be used. These expressions and
examples are shown in Table 12.4.
 The symbol % used without qualificati
on (as with w/v, v/v, or w/w) means
 percent weight in volume for solutions
or suspensions of solids in liquids;
 percent weight in volume for solutions
of gases in liquids;
 percent volume in volume for solution
s of liquids in liquids;
 and weight in weight for mixtures of s
olids and semisolids.
 To hasten dissolution, a pharmac
ist may employ one of several tec
hniques, such as
 applying heat,
 reducing the particle size of the s
olute,
 using a solubilizing agent,
 or subjecting the ingredients to v
igorous agitation.
 Most chemical agents are more
soluble at elevated temperatures
than at room temperature or below
because an endothermic reaction
between the heat to enhance
dissolution.

 In addition to or instead of raising

the temperature of the solvent to
increase the rate of solution, a
pharmacist may choose to decrease
the particle size of the solute.
 Most solutions are prepared by
simple mixing of the solutes with
the solvent.

 On an industrial scale, solutions

are prepared in large mixing
vessels with ports for mechanical
stirrers.
 4. Oral Solutions and Preparations for
Oral Solution
 Most solutions intended for oral a
dministration contain flavorants a
nd colorants to make the medicat
ion more attractive and palatable.
 When needed, they may also cont
ain stabilizers to maintain the ch
emical and physical stability of th
e medicinal agents and preservati
ves to prevent the growth of micr
oorganisms in the solution.
 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.

 Liquid pharmaceuticals for oral

administration are usually formulated
such that the patient receives the
usual dose of the medication in a
conveniently administered volume, as
5mL, 10mL, or 15mL.
 (1) Dry Mixtures for Solution
 A number of medicinal agents,
particularly certain antibiotics, have
insufficient stability in aqueous
solution to meet extended shelf life
periods.
 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, incl
uding drug, flavorant, colorant, buff
ers, and others, except for the solve
nt.

 Once reconstituted by the pharmaci

st, the solution remains stable when
stored in the refrigerator for the lab
eled period, usually 7 to 14 days, de
pending on the preparation.
 (2) Oral Solutions

 The pharmacist shoule be sufficientl

y knowledgeable about the dispense
d product to expertly advise the pati
ent of the proper use, dosage, meth
od of administration and storage of
the product.

 Table 12.5 presents examples of so

me oral solutions.
Knowledge of
 the solubility and stability

characteristics of the medicinal

agents
 and the solvents employed in the

commercial products
 is useful to the pharmacist for

informing the patient of the

advisability of mixing the solution
with juice, milk, or other beverage
upon administration.
 (3) Oral Rehydration Solutions
 Rapid fluid loss associated with
diarrhea can lead to dehydration and
ultimately death in some patients,
particularly infants.

 Diarrhea is characterized by an
increased frequency of loose, watery
stools, and because of the rapid fluid
loss, dehydration can be an outcome.
 During diarrhea, the small intestine s
ecretes far more than the normal amo
unt of fluid and electrolytes, and this s
imply exceeds the ability of the large i
ntestine to reabsorb it.

 This fluid loss, which occurs mostly fr

om the body’s extracellular fluid comp
artment, can lead to a progressive los
s of blood volume culminating in hypo
volemic shock.
 Oral rehydration solutions are usually
effective in treatment of patients with
mild volume depletion, 5 to 10% of bod
y weight.

 A liter or typical oral rehydration solut

ion contains 45 mEq Na+, 20 mEq K+, 3
5 mEq Cl-, 30 mEq citrate, and 25 g de
xtrose.

 It is important that the user add the sp

ecific amount of water needed to prepa
re the powder forms.
 (4) Magnesium Citrate Oral Solution

 Magnesium citrate oral solution is

a colorless to slightly yellow, clear,
effervescent liquid having a sweet,
acidulous taste and a lemon flavor.

 The solution is employed as a salin

e cathartic with the citric acid, le
mon oil, syrup, carbonation.
The solution is prepared by
 reacting official magnesium

carbonate with an excess of citric

acid,
 flavoring and sweetening the

solution with lemon oil and syrup,

 filtering with talc,

 and then carbonating it by the

addition of either potassium or

sodium bicarbonate.
 (5) Oral Colonic Lavage Solution

Polyethylene glycol 3350 236.00 g

Sodium sulfate 22.74 g
Sodium bicarbonate 6.74 g
Sodium chloride 5.86 g
Potassium chloride 2.97 g

In 4800 ml disposable container

he PEG acts as an osmotic agent within the

strointestinal tract and the balanced electroly
ncentration results in virtually no net absorpti
secretion of ions.
 (6) Sodium Citrate and Citric Acid Oral
Solution

The solution is administered orally

in doses of 10 to 30 ml/4 times.

Systemic
alkalinization

Uric acid
1 ml aqueous solution Cystine calculi
100 mg sodium citrate
67 mg citric acid
 5. Syrups
 Syrups are concentrated aqueous
preparations of a sugar or sugar s
ubstitute with or without flavorin
g agents and medicinal substance
s.

 Syrups containing flavoring agent

s but not medicinal substances ar
e called nonmedicated or flavored
vehicles (syrups).
Medicated
syrups

sucrose
purified water
flavoring agents
coloring agents
therapeutic agent
 Syrups provided 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.
 Any water-soluble drug that is st
able in aqueous solution may be
added to a flavored syrup.

 However, care must be exercised

to ensure compatibility between t
he drug substance and the other
formulative components of the sy
rup.
 (1) Components of Syrups
Most syrups contain the followin
g components in addition to the
purified water and any medicinal
agents present:
Sugar
Antimicrobial Pres
ervatives
Flavorant
Colorants
Sucrose and non-sucrose
based syrup

Sucrose Non-sugars
Non-sugars
Sucrose
Dextros Sorbitol
Sorbitol
Dextros
ee Glycerin
Glycerin
Propylene
Propylene gl
gl
ycol
ycol

Methylcellulose
Methylcellulose
Hydroxyethylcell
Hydroxyethylcell
ulose
ulose
 Most syrups contain a high
proportion of sucrose, usually 60-
80%.
 Concentrated sugar solutions are
quite resistant to microbial growth.

Simple syrup
85 g sucrose
+purified water
=100 ml syrup
 Antimicrobial preservative

Benzoic acid (0.1 to 0.2%)

Sodium benzoate (0.1 to 0.2%)
Methyl-, propyl-, and butylparabens (0.1%)
Alcohol (15 to 20%)
Syrups can be preserved by
1) storage at low temperature

2) adding preservatives in the

formulation
3) by the maintenance of a high
concentration of sucrose as a
part of the formulation
 Example

Rx
Active drug 5ml volume occupied
Other drug solids 3 ml volume occupied
Glycerin 15 ml
Sucrose 25 g
Ethanol 95% q.s.
Purified water q.s. 100 ml

How much alcohol would be required to

preserve this prescription?
 Flavorant

Synthetic flavorants
Naturally occurring materials
Volatile oils
Vanillin

Because syrups are aqueous preparation

s, these flavorants must be water soluble.
 Colorant
The colorant is generally
 water soluble,

 nonreactive with the other syrup

components,
 color stable at the pH range and

under the intensity of light that t

he syrup is likely to encounter du
ring its shelf life.
green with mint
brown with chocolat
 (2) Preparation of Syrups
Syrups are frequently prepared by
one of four general methods.
1) solution of the ingredients with the aid
of heat,
2) solution of the ingredients by agitation
without the use of heat, or the simple a
dmixture of liquid components,
3) addition of sucrose to a prepared medic
ated liquid or to a flavored liquid,
4) percolation of either the source of the
medicating substance or of the sucrose.
 Ⅰ. Solution With the Aid of
Heat

Syrups are prepared by this

method
 when it is desired to prepare the

syrup as quickly as possible,

 when the syrup’s components

are not damaged or volatilized

by heat.
 In this method the sugar is gen
erally added to the purified wat
er, and heat is applied until the
sugar is dissolved.
 then other heat-stable compone
nts are added to the hot syrup,
 the mixture is allowed to cool,
 its volume is adjusted to the pro
per level by addition of purified
water.
 If heatlabile agents or volatile sub
stances, such as volatile flavoring
oils and alcohol, are to be added,

 they are generally added to the syr

up after the sugar is dissolved by
heat,

 and the solution is rapidly cooled t

o room temperature.
 Because of the prospect of
decomposition by heat, syrups
cannot be sterilized by autoclaving.
 The use of boiled purified water in
the preparation of a syrup can
enhance its permanency, and the
addition of preservative agents,
when permitted, can protect it
during its shelf life.
 Storage in a tight container is a
requirement for all syrups.
Ⅱ. Solution by Agitation Witho
ut the Aid of Heat
 To avoid heat-induced inversion
of sucrose, a syrup may be prepa
red without heat by agitation.

 On a small scale, sucrose and oth

er formulative agents may be dis
solved in purified water and thor
ough agitated of the mixture.
 This process is more time consuming than
use of heat, but the product has maximum
stability.

 Huge glass-lined or stainless steel tanks with

mechanical stirrers or agitators are
employed in large-scale preparation of
syrups.

 When solid agents are to be added to a syrup,

it is best to dissolve them in a minimal
amount of purified water and incorporate the
resulting solution into the syrup.
Ⅲ. Addition of Sucrose to a Me
dicated Liquid or to a Flavored
Liquid
 Occasionally a medicated liquid, su
ch as a tincture or fluidextract, is e
mployed as the source of medicatio
n in the preparation of a syrup.

 Many such tinctures and fluidextrac

ts contain alcohol-soluble constitue
nts and are prepared with alcoholic
or hydroalcoholic vehicles.
 If the alcohol-soluble component
s are desired medicinal agents, s
ome means of rendering them wa
ter soluble is employed.

 If the tincture or fluidextract is

miscible with aqueous preparatio
ns, it may be added derectly to si
mple syrup or to a flavored syrup.
 Ⅳ. Percolation （渗漉）
 In the percolation method, 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.

 This latter method really is two

separate procedures: first the
preparation of the extractive of the
drug and then the preparation of the
syrup.
 Ipecac syrup
Percolation

Glycerin Extractive
Syrup of powdered ipecac

alkaloids
alkaloids
Ipecac emetine
emetine
dried rhizome cephaelin
cephaelin
roots of cephaelis ipecacuanha ee
psychotri
psychotri
ne
ne
 The usual dose of ipecac syrup is 15
ml.

 This amount of syrup is commonly u

sed in the management of poisoning
in children when the evacuation of t
he stomach contents is desirable.

 Ipecac syrup also has some applicati

on as a nauseant expectorant, in dos
es smaller than the emetic dose.
 6. Elixirs
 Elixirs are clear, sweetened hydr
oalcoholic solutions intended fo
r oral use and are uaually flavore
d to enhance their palatability.
 Nonmedicated elixirs are employ
ed as vehicles;
 Medicated elixirs are used for th
e therapeutic effect of the medici
nal substances they contain.
 Compared with syrups, elixirs are
usually less sweet and less viscous.

 Elixirs are better able than aqueous

syrups to maintain both water-
soluble and alcohol-soluble
components in solution.

 Each elixir requires a specific blend

of alcohol and water to maintain all
of the components in solution.
 In addition to alcohol and water,
other solvents, such as glycerin a
nd propylene glycol, are frequentl
y employed in elixirs as adjunctiv
e solvents.

 Although many elixirs are sweete

ned with sucrose or with a sucros
e syrup, some use sorbitol, glycer
in, and/or artificial sweeteners.
 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.
 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.
 Elixirs should be stored in tight,
light-resistant containers and
protected from excessive heat.
 (1) 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 to maintain
the highest possible alcoholic
strength at all times so that minimal
separation of the alcohol-soluble
components occurs.

 When the two solutions are

completely mixed, the mixture is
made to volume with the specified
solvent or vehicle.
Frequently the final mixture will
be cloudy because of separation
of some of the flavoring oils by
the reduced alcoholic
concentration.

Talc
Filter
 (2) Nonmedicated Elixirs

Nonmedicated elixirs may be us

eful to the pharmacist in the ext
emporaneous filling of prescript
ions involving
(a) the addition of a therapeutic ag
ent to a pleasant-tasting vehicle,
(b) dilution of an existing medicate
d elixir.
 In selecting a liquid vehicle for a
drug substance, the pharmacist s
hould be concerned with the solu
bility and stability of the drug su
bstance in water and alcohol.

 All components should be chemic

ally and physically compatible.
 The three most commonly used n
onmedicated elixirs were
 aromatic elixir,
 compound benzaldehyde elixir （复
方安息香醛酏剂） ,
 isoalcoholic elixir.
 (3) Medicated Elixirs
 Antihistamines elixirs are useful
primarily in the symptomatic
relief of certain allergic disorders.
 The most common untoward
effect is sedation.
 Other common adverse effects
include dryness of the nose,
throat, and mouth; dizziness; and
disturbed concentration.
 Barbiturate sedative/hypnotic
elixirs
 Barbiturates are administered in small
doses in the daytime hours as sedatives
to reduce restlessness and emotional
tension.
 Greater doses may be given before
bedtime as hypnotics to release
insomnia.
long-acting phenobarbital
intermediate-acting amobarbital
short-acting pentobarbitol
ultrashort-acting secobarbitol
thiopental
 Phenobarbital Elixir
 Phenobarbital elixir is formulated to
contain phenobarbital 0.4%,which pr
ovides about 20 mg of drug per teas
poonful (5mL)of elixir.

Orange oil
Colored red
Syrup
Glycerin
 Digoxin Elixir
Digoxin is poisonous, and its dose m
ust be carefully determined and adm
inistered to each individual patient.
The official elixir contains about 10% of al
cohol.
Droppe
Droppe
rr

100 ml elixir Cardiotonic agent

4.5 mg to 5.25 mg 1.5 mg initial therapy
0.25 mg/5mL teaspoonful0.5 mg maintenance therapy
 7. Tinctures
 Tinctures are alcoholic or hydroa
lcoholic solutions prepared from
vegetable materials or from che
mical substances.

 They vary in method of preparati

on, strength of the active ingredi
ent, alcoholic content, and inten
ded use in medicine or pharmacy.
 Depending on the praparation, tinctu
res contain alcohol in amounts rangi
ng from approximately 15 to 80%.

 The alcohol content protects against

microbial growth and keeps the alco
hol-soluble extractives in solution.

 In addition to alcohol, other solvents,

such as glycerin, may be employed.
 Tinctures must be tightly stoppered
and not exposed to excessive temper
atures.

 Many tinctures must be stored in lig

ht-resistant containers and protecte
d from sunlight.

paregoric
camphorated
tincture of opium
 8. Proper Administration and
Use of Liquid Peroral Dosage F
orms
 The liquid dosage forms should be
measured out in calibrated devices
for administration.

 Even though these are liquids, it is

recommended that the patient
follow the administration of the
liquid dosage form with a glassful
of water.
 The pharmacist must be careful in
the selection of liquid products
given the patient’s history and
other concurrent medicines.

Diabetic patient
Antabuse-like activity
Another drug-drowsiness
 9. Topical Solutions and
Tinctures
 Generally, the topical solutions e
mploy an aqueous vehicle, wherea
s the topical tinctures characteris
tically employ an alcoholic vehicle.

 As required, cosolvents or adjunct

s to enhance stabililty or the solu
bility of the solute are employed.
 Most topical solutions and
tinctures are prepared by simple
dissolving. However, certain
solutions are prepared by
chemical reaction.

 Because of the nature of the

active constituents or the
solvents, many topical solutions
and tinctures are self-preserved.
 (1) Sprays
 Sprays may be defined as aqueous or
oleaginous solutions in the form of c
oarse droplets or as finely divided sol
ids to be applied topically, most usua
lly to the nasopharyngeal tract or to
the skin.
 Many commercial sprays are used in
tranasally to relieve nasal congestio
n and inflammation and to combat in
fection and contain antihistamines, s
ympathomimetic agents, and antibio
tic substances.
 Other sprays that are employed ag
ainst sunburn and heat burn conta
in local anesthetics, antiseptics, sk
in protectants, and antipruritics.

 Throat sprays containing antisepti

cs, deodorants, and flavorants may
be effectively employed to relieve c
onditions such as halitosis, sore th
roat, and laryngitis.
 Other sprays treat athlete’s foot
and other fungal infections.

 Recently, one-way pump sprays

have been developed to deliver
medication into the nose.
 (2) Aluminum Acetate Topical
Solution
 Aluminum acetate is colorless and
has a faint acetous odor and a
sweetish, astringent taste.

 It is widely applied topically as an

astringent wash or wet dressing after
dilution with 10 to 40 parts of water.

 It is frequently used in various types

of dermatologic lotions, creams, and
pastes.
(3) Aluminum Subacetate Topical
Solution
 Aluminum subacetate （碱式醋酸铝） top
ical solution, is used in prepatatio
n of aluminum acetate topical sol
ution.

 Aluminum acetate topical solutio

n, diluted first with 20 to 40 parts
of water, is used externally as an
astringent wash and wet dressing.
(4) Calcium Hydroxide Topical
Solution
 Calcium hydroxide topical solutio
n, commonly called limewater, m
ust contain not less than 140 mg
of Ca(OH)2 in each 100 mL of sol
ution.
 Calcium hydroxide is less soluble
in hot than in cold water, and coo
l purified water is the solvent.
 The solution should be stored in wel
l-filled, tightly stoppered containers
to deter the absorption of carbon dio
xide and should be kept in a cool pla
ce to maintain an adequate concentr
ation of dissolved solute.
 The solution is categorized as an ast
ringent. For this purpose it is genera
lly employed in combination with oth
er ingredients in dermatologic soluti
ons and lotions to be applied topicall
y.
(5) Coal Tar Topical Solution
 Coal tar topical solution is an alcoh
olic solution containing 20% coal t
ar and 5% polysorbate 80. The final
content is 81 to 86% ethyl alcohol.
 Coal tar is a nearly black viscous li
quid having a characteristic naphth
alene-like odor and a sharp, burnin
g taste.
 It is slightly soluble in water and p
artially soluble in most organic solv
ents, including alcohol.
 Coal tar is a local antieczematic.

 The solution is used in external t

reatment of a wide variety of chr
onic skin conditions after dilutio
n with about 9 volumes of water,
or in combination with other age
nts in various lotions, ointments
or solutions.
(6) Hydrogen Peroxide Topical
Solution
 Hydrogen peroxide topical solution
contains 2.5 to 3.5%(w/v) hydrogen
peroxide, or H2O2 .
 The solution is a clear, colorless
liquid that may be odorless or have
the odor of ozone.
 It usually deteriorates upon long
standing , forming oxygen and
water.
 Preservative agents, such as
acetanilide, have been found to
retard decomposition.

 Decomposition is enhanced by light

and by heat, and for this reason the
solution should be preserved in
tight, light-resistant containers,
preferably at a temperature not
exceeding 35℃.
 The solution is also decomposed by p
ractically all organic matter and othe
r reducing agents and reacts with oxi
dizing agents to liberate oxygen and
water; metals, alkalies, and other age
nts can catalyze its decomposition.

 Hydrogen peroxide solution is catego

rized as a local anti-infective for use
topically on the skin and mucous me
mbranes.
(7) Chlorhexidine Gluconate S
olution
 Chlorhexidine gluconate has bee
n employed extensively as a broa
d-spectrum antiseptic in clinical
and veterinarian medicine.

 Its spectrum encompasses gram-

positive and gram-negative bacte
ria, including Pseudomonas aeru
ginosa.
 In a concentration of 4% (Hibiclins, S
tuart) it is used as a surgical scrub, h
and wash, and skin wound and gener
al skin cleanser.
 The most common side effect of chlo
rhexidine is the formation of an extri
nsic yellow-brown stain on the teeth
and tongue after only a few days of u
se.
 The developed stain can be periodica
lly removed with dental prophylaxis.
(8) Povidone Iodine Topical So
lution
 The agent povidone iodine is a chemical c
omplex of iodine with polyvinylpyrrolidone.
 The povidone iodine complex contains app
roximately 10% available iodine and slowl
y releases it when applied to the skin.
 The preparation is employed topically as a
surgical scrub and nonirritating antisepti
c solution, with its effectiveness directly a
ttributable to the presence and release of
iodine from the complex.
 (9) Thimerosal （硫柳汞） Topical Solut
ion
 Thimerosal is a water-soluble orga

nic mercurial antibacterial agent

used topically for its bacteriostati
c and mild fungistatic properties.
 It is used mainly to disinfect skin

and as an application to wounds a

nd abrasions.
 It has been applied to the eye, nos

e, throat, and urethra in dilutions

of 1:5000.
 It is also used as a preservative f
or various pharmaceutical prepar
ations.
The solution
must be
maintained in
light-resistant
0.1% Thimerosal containers
Ethylene diamine solution
Sodium borate
Monoethanolamine
 Thimerosal topical solution conta
ins 0.1% thimcrosal.

 The solution is affected by light a

nd must be maintained in light-r
esistant containers.
 10. Vaginal and Rectal
Solutions
(1) Vaginal Douches
 Solutions may be prepared from p
owders as indicated earlier or fro
m liquid solutions or liquid concen
trates.
 In using liquid concentrates , the
patient is instructed to add the pr
escribed amount of concentrate to
a certain amount of warm water.
 The user simply adds the prescribed amount of powd
er to the appropriate volume of warm water and stirs
until dissolved.
 Among the components of douche powders are the fo
llowing:
1. Boric acid or sodium borate
2. Astringents
3. Antimicrobials
4. Quaternary ammonium compounds
5. Detergents
6. Oxidizing agents
7. Salts, e.g. ,sodium citrate, sodium chloride
8. Aromatics, e.g. , menthol, thymol.
 (2) Retention Enemas
 A number of solutions are administered
hydrocorti
rectally for the local sone
effects of the
aminophyll
ine
medication or for systemic absorption.

 Clinically effective blood levels of the agents

are usually obtained within 30 minutes
following rectal instillation.
 (3) Evacuation Enemas
 Rectal enemas are used to cleanse the bowel.
 The agents present are
- solutions of sodium phosphate and sodium b
iphosphate
- glycerin and docusate potassium
- light mineral oil
 The patient should be advised to gently
insert the tip of the product with steady
pressure and be told that it is not absolutely
necessary to squeeze all of the contents out
of the disposable plastic bottle.

 The patient should be told that the product

will most probably work within 5 to 10
minutes.
 11. Topical Tinctures
(1) Iodine Tincture

2% iodine crystals I2+NaINaI3

2.4% sodium iodide This reaction prevents the
Alcohol formation of ethyl iodide from th
interaction between iodine and th
Purified water
alcohol, which would result in th
loss of the antibacterial activity o
The tincture.
 The tincture is a popular local an
ti-infective agent applied to the s
kin, is useful in delineating the a
pplication over the affected skin
area.

 The tincture should be stored in

a tight container to prevent loss
of alcohol.
 (2) Compound Benzoin Tincture

Maceration in alcohol of 10% benzoin

24% aloe, storax and tolu balsam

The tincture is categorized as a protectant.

Itis used to protect and toughen skin in t

he treatment of
bedsores, ulcers, cracked nipples, and fiss
ures of the lips
and anus.
 It is also commonly used as an inh
alant in bronchitis and other respi
ratory conditions.

 Compound tincture of benzoin ser

ves as a delivery vehicle of podoph
yllum in the treatment of venereal
warts.
 (3) Thimerosal Tincture
 The commercial
preparation is colored
orange red and has
greenish fluorescence. 0.1% Thimerosal
 The red stain it leaves on Monoethanolamine
the skin defines the area Distilled water
of application. Acetone
 It is a commonly used 50% alcohol
household antiseptic for
application to abrasions
and cuts and also in
preparation of patients
for surgery.
 12. Special application solutions

(1) nasal preparations

 The vast majority of preparations
intended for intranasal use contain
adrenergic agents and are
employed for their decongestant
activity on the nasal mucosa.
Nose drops
Sprays
Jellies
Nasal decongestant solutions
Most nasal decongestant solutions are
 aqueous preparations

 rendered isotonic to nasal fluids

(approximately equivalent to 0.9%

sodium chloride),
 buffered to maintain drug stability

(pH5.56.5)
 stabilized and preserved as required.
 Most of the adrenergic drugs
used in nasal decongestant
solutions are synthetic
compounds epinephrine.
 Most solutions for nasal use are
packaged in dropper bottles or in
plastic spray bottles, usually
containing 15 to 30 ml of
medication.
 The concentration of adrenergic agent
is ranging from about 0.05 to 1.0%.
 Nasal decongestant solutions are
employed in the treatment of rhinitis
of the common cold and for vasomotor
and allergic rhinitis including hay
fever, and for sinusitis.
 The frequent use or their use for
prolonged periods may lead to chronic
edema of the nasal mucosa. Thus, they
are best used for short periods (no
longer than 3 to 5 days).
 （ 2 ） Otic Solution
 Ear preparations are usually plac
ed in the ear canal by drops or in
small amounts for the removal of
excessive cerumen (ear wax) or f
or the treatment of ear infections,
inflammation, or pain.
 Cerumen-removing solutions
Light mineral oil
Vegetable oils Solution of
Hydrogen peroxide Synthetic surfactants
 Commercial products

1) Triethanolamine polypeptide
oleate-condensate in propylene glycol
2) Carbamide peroxide in glycerin/
Propylene glycol
 Anti-infective, anti-inflammatory,
and analgesic ear preparations
 Drugs used topically in the ear fo
r their antiinfective activity inclu
de
 chloramphenicol
 colistin sulfate
 neomycin
 polymyxin B sulfate
 nystatin
 Anti-inflammatory agents
-Hydrocortisone
-Dexamethasone sodium phosphate
-Acetic acid (2%) in aluminum
acetate solution
-Boric acid (2.75%) in isopropyl alcohol

Topical analgesics
antipyrine
local anesthetic benzocaine
in a vehicle of propylene glycol
or anhydrous glycerin
Preservation
 Chlorobutanol (0.5%)

 Thimerosal (0.01%)

 Combinations of the parabe

ns
Antioxidants
 Sodium bisulfite

Stabilizers
 13. Miscellaneous Solutions

(1) Aromatic Waters

 Aromatic waters are clear, aqueo
us solutions saturated with volati
le oils or other aromatic or volatil
e substances.

 Aromatic waters may be used for

perfuming and/or flavoring.
 (2) Diluted Acids
 Diluted acids are aqueous solutions pr
epared by diluting the corresponding
concentrated acids with purified water.
 The strength of a diluted acid is gener
ally expressed on a percent weght-to-v
olume (% w/v) basis, that is, the weigh
t in grams of solute per 100 mL of sol
ution,
 whereas the strength of a concentrate
d acid is generally expressed in terms
of percent weight to weight (% w/w), w
hich indicates the number of grams of
solute per 100 g of solution.
 To prepare a diluted acid from a
concentrated one, it is necessary
first to calculate the amount of
solute required in the diluted
product.

 Then the amount of concentrated

acid required to supply the needed
amount of solute can be determined.
 To illustrate, concentrated hydrochlori
c acid (HCl) contain not less than 35 g
and not more than 38 g of solute per 1
00 g of acid and therefore is considere
d to be, on the average, 36.5% w/w in s
trength.
 Diluted HCl contains 9.5 to 10.5 g of so
lute per 100 mL of solution and is ther
efore considered to be approximately 1
0% w/v in strength.
 If one wished to prepare 100mL of the
diluted acid from the concentrated aci
d, one would
 require 10 g of solute. The amount of co
ncentrated HCl required to supply this a
mount of solute may be calculated by the
following proportion:

Thus, 27.39 g of concentrated acid is req

uired to supply 10 g of solute needed for
the preparation of 100 mL of the diluted
acid.
 Concentrated sulfuric acid 95-98% (w/w)
Concentrated nitric acid 69-71% (w/w)
Concentrated phosphoric acid 85-88% (w/w)
 (3) Spirits
 Spirits are alcoholic or hydroalcoholi
c solutions of volatile substances.
 Generally, the alcoholic concentratio
n of spirits is rather high, usually ov
er 60%.
 Because of the greater solubility of a
romatic or volatile substances in alco
hol than in water, spirits can contain
a greater concentration of these mat
erials than the corresponding aroma
tic waters.
 Spirits may be used pharmaceutically
as flavoring agents and medicinally
for the therapeutic value of the
aromatic solute.
 For medicinal purposes, spirits may
be taken orally, applied externally, or
used by inhalation, depending upon
the particular preparation.
 When taken orally, they are generally
mixed with a portion of water to
reduce the pungency of the spirit.
 14. Nonaqueous Solutions
(1) Liniments （搽剂）
 Liniments are alcoholic or oleagi
nous solutions or emulsions of va
rious medicinal substances inten
ded to be rubbed on the skin.
 Liniments are useful when rubefa
cient, counterirritant, or penetrat
ing action is desired; oleaginous
liniments are employed primarily
when massage is desired.
  All liniments should bear a label
indicating that they are suitable
only for external use and must
never be taken internally.
Oleaginous liniments
The solvent may be fixed oil such as
almond oil
peanut oil
sesame oil
cottonseed oil
olatile substance such as winter-green oil or turpentin
 (2) Collodions （火棉胶）
 Collodions are liquid preparations c
omposed of pyroxylin （硝酸纤维素） disso
lved in a solvent mixture usually co
mposed of alcohol and ether with or
without added medicinal substances.
 Pyroxylin, like collodions, is exceedi
ngly flammable and must be stored
away from flame in well-closed cont
ainers, protected from light.
 Collodions are intended for external
use.
Collodion
 Collodion is a clear or slightly op

alescent viscous liquid .

 The product is capable of formin

g a protective film on application

to the skin and the volatilization
of the solvent. The flim is useful i
n holding the edges of an incised
wound together.
 However, its presence on the ski

n is uncomfortable because of its

inflexible nature.
Flexible collodion （弹性火棉胶）
 Flexible collodion is prepared by

adding 2% camphor and 3% casto

r oil to collodion.
 The castor oil renders the produc

t flexible, permitting its comforta

ble use over skin areas that are n
ormally moved, such as fingers a
nd toes. The camphor makes the
product waterproof.
Salicylic acid coilodion
 It is used for its keratolytic effects,

especially in the removal of corns fr

om the toes.
 The product should be applied one

drop at a time on the corn or wart, a

llowing time to dry before the next
drop is added.
 Proper tightening and storage of th

e product after use are absolutely n

ecessary because of the volatility of
the vehicle.
15. Extraction Methods for Preparing Solutions

Certain pharmaceutical
preparations are prepared by
extraction, that is, by withdrawal
of desired constituents from
crude drugs through the use of
selected solvents in which the
desired constituents are soluble.
Water
Hydroalcoholic mixtures
Glycerin
 Methods of Extraction
 The principal methods of drug
extraction are maceration and
percolation.
 Generally, the method of extraction
selected for a given drug depends on
several factors, including the nature
of the crude drug, its adaptability to
each of the various extraction
methods, and the interest in
obtaining complete or nearly
complete extraction of the drug.
 (1) Maceration （浸渍）
 It is a process in which the prope
rly comminuted drug is permitte
d to soak in the menstruum until
the cellular structure is softened
and penetrated by the menstruu
m and the soluble constituents ar
e dissolved.
 For drugs containing little or no ce
llular material, such as benzoin （安息
香） , aloe （芦荟） , and tolu （妥鲁香 ） , whi
ch dissolve almost completely in th
e menstruum, maceration is the m
ost efficient method of extraction.

 Maceration is usually conducted at

a temperature of 15℃ to 20 ℃ for
3 days or until the soluble matter i
s dissolved.
 (2) Percolation （渗漉）
 It may be described generally as a
process in which a comminuted drug
is extracted of its soluble constituents
by the slow passage of a suitable
solvent through a column of the drug.
 The drug is packed in a special
extraction apparatus termed a
percolator, with the collected
extractive called the percolate.
 Most drug extractions are performed
by percolation .
 In the process of percolation the flow
of the menstruum over the drug colu
mn is generally downward to the exit
orifice, drawn by the force of gravity
as well as the weight of the column o
f liquid.

 In certain specialized and more sophi

sticated percolation apparatus, additi
onal pressure on the column is exert
ed with positive air pressure at the in
let and suction at the outlet or exit.
 Percolators for drug extraction var
y greatly as to their shape, capaciti
es, composition, and, most importa
nt utility.

 Percolators employed in the large-

scale industrial preparation of extr
active are generally stainless steel
or glasslined metal vessels that var
y greatly in size and in operation.
 Percolation on a small scale gene
rally involves the use of glass per
colators of various shapes for ext
raction of small amounts (perhap
s up to 1000 g) of crude drug.

 The cylindrical percolator is parti

cularly suited to the complete ext
raction of drugs with a minimal e
xpenditure of menstruum.
Example preparations prepare
d by extraction processes

 Fluidextracts
 Extracts
 Questions
1. How to prepare purified water?
2. What solvents are commonly us
ed for liquid preparations?
3. What are elixirs and tinctures?
4. Please give examples to explain
how to prepare medicated elixir
s and tinctures?