SOLVENTS USED IN

PHARMACEUTICAL
PREPARATIONS

PHARM.D 3rd Semester

SOLVENTS USED IN
PHARMACEUTICAL PREPARATIONS
 Pharmacist knowledge of the physical and chemical
characteristics of the given drug dictates selection of
appropriate solvent for a particular formulation.

 In addition to solubility solvent selection is also based on

clarity, toxicity, viscosity, compatibility with excipients,
chemical inertness, palatability, odor, color and
economy.

 In most cases, especially solutions for oral, intranasal,

opthalmic or parenteral administration, water is the
preferred solvent because it meets majority of the above
criteria better than other solvents.
 SOLVENTS USED IN
PHARMACEUTICAL PREPARATIONS

 Solvents such as acetone, ethyl oxide and isopropyl

alcohol are too toxic for use in oral pharmaceutical
preparations, but the are useful solvents in organic
chemistry and in preparatory stages of drug
development.

 A number of fixed oils serves useful solvent functions

particularly in the preparation of oleaginous injections.
 The solvent
System

Aqueous Non-aqueous
solvents solvents

Purified water
Alcohols
Water for injection
Esters
Sterile water for injection Fixed oils
Bacteriostatic water for Dimethyl sulfoxide
injection
Ethyl ether
Sterile water for inhalation
Sterile water for irrigation
Sterile purified water
 Solvents • Water, ethyl alcohol,
for oral glycerine, propylene
preparatio glycol, olive oil, ethyl
oleate etc
n
Solvents • Industrial methylated
for spirit, isopropyl alcohol,
external benzyl alcohol,
preparatio polyethylene glycols,
myrestic acid etc
n
Solvents
• Water for injection, ethyl
for oleate, olive oil, arachis
parenteral oil, propylene glycol,
preparatio glycerol
n
AQUEOUS SOLVENTS
 The major ingredient in most of the pharmaceutical dosage
forms is water

 It is used both as a vehicle and as a solvent for the desired

flavoring or medicinal ingredients.

 Ordinary drinking water from the tap is not acceptable for

the manufacture of most aqueous pharmaceutical
preparations or for extamporaneous compounding of
prescriptions, as it contains dissolved substances which
could interfere with the formulation (e.g. reduce drug
solubility and stability)
AQUEOUS SOLVENTS
 The USP recognizes seven different types of water for the
preparation of dosage forms based on their purity:

 Purified water USP is water obtained by distillation, ion

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

 Water for injection USP is water obtained by distillation or by

reverse osmosis. It conforms to the standards of purified water but
is also free of pyrogen. Water for injection is used as a solvent for
the preparation of parenteral solutions.
AQUEOUS SOLVENTS
 Sterile water for injection USP is water for injection
that is sterilized and packaged in single-dose containers
of type I and II glass. These containers do not exceed a
capacity of 1 L. The limitations for total solids depend
on the size of the container.

 Bacteriostatic water for injection USP is sterile water

for injection that contains one or more suitable
antimicrobial agents. It is also packaged in single- or
multiple-dose containers of type I or II glass. These
containers do not exceed the capacity of 30 mL.
AQUEOUS SOLVENTS
 Sterile water for inhalation USP is water that is
purified by distillation or by reverse osmosis (i.e., water
for injection) and rendered sterile. It contains no
antimicrobial agents, except when used in humidifiers or
similar devices. This type of water should not be used for
parenteral administration or for other sterile dosage
forms.

 Sterile water for irrigation USP is water for injection

that is sterilized and suitably packaged. It contains no
antimicrobial agents or other added substance.
AQUEOUS SOLVENTS

 Sterile purified water USP is purified water sterilized

and suitably packaged. It contains no antimicrobial
agent. It is not intended for use in parenterals.
NON-AQUEOUS SOLVENTS:

 Non-aqueous solvent systems are used when the drug is

insufficiently soluble or stable in aqueous systems

 There are a huge number of organic liquids in which drugs

can dissolve, but the majority are toxic and only a few are
used in pharmaceutical solutions.

 Limited to certain delivery routes due to their un-palatability,

toxicity, irritancy or immiscibility with physiological fluids

 These are used as co-solvents with water, as co-solvents with

other liquids or on their own.
NON-AQUEOUS SOLVENTS:

 ALCOHOL, USP: ETHYL ALCOHOL, ETHANOL, C2 H5

OH

 Alcohol, USP, is 94.9% to 96.0% C2H5OH by volume when

determined at 15.56°C, the U.S. government’s standard
temperature for alcohol determinations. Dehydrated Alcohol, USP,
contains not less than 99.5% C2H5OH by volume and is used
when an essentially water-free alcohol is desired.
 Next to water, alcohol is the most useful solvent in pharmacy
 Alcohol has been well recognized as a solvent and excipient in the
formulation of oral pharmaceutical products.
 It is often used as a co-solvent in oral, topical and parenteral
solutions
…

 Often preferred because of its miscibility with water and

its ability to dissolve many water-insoluble ingredients,
including drug substances, flavorants, and antimicrobial
preservatives
 Together with water, it forms a hydroalcoholic mixture
that dissolves both alcohol-soluble and water-soluble
substances
 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, and other agents.
…
 Aside from its pharmaceutical advantages as a solvent
and a preservative, concern has been expressed over the
undesired pharmacologic and potential toxic effects of
alcohol when ingested in pharmaceutical products,
particularly by children
…
 DILUTED ALCOHOL NF:

 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.
 Diluted alcohol is a useful hydroalcoholic solvent in
various pharmaceutical processes and preparations.
…
 RUBBING 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.

 Rubbing alcohol USP, must be manufactured in

accordance to the requirements of Internal Revenue
Service, U.S. Treasury Department, formula 23-H.

 The use of this denaturant mixture makes the separation of

ethyl alcohol from the denaturants virtually impossible
with ordinary distillation apparatus
…
 The product is volatile and flammable and should be
stored in a tight container remote from fire.

 It is employed as a rubefacient externally and as a

soothing rub for bedridden patients, a germicide for
instruments, and a skin cleanser prior to injection.

 It is also used as a vehicle for topical preparations

…
 GLYCERIN, USP (GLYCEROL):
 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 (cosolvent) in
conjunction with water or alcohol.
 It is used in many internal preparations
…
 ISOPROPYL RUBBING ALCOHOL:
 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 a rubefacient and soothing rub

and as a vehicle for topical products.
…
 PROPYLENE GLYCOL, USP
 Propylene glycol, a viscous liquid, is miscible with water
and alcohol.

 It is often used as a cosolvent in oral, parenteral, topical

and otic solutions.

 It is a useful solvent with a wide range of applications

and is frequently substituted for glycerin in modern
pharmaceutical formulations.
…
 FIXED OILS:
 Fixed oils are expressed from the seeds, fruit or pit/stone/kernel of
various plants

 Historically they have been used for intramuscular administration,

but now they are used to lesser extent because of their irritancy
and possibility of allergic reactions to certain oils

 They are being replaced by synthetic alternatives such as ethyl

oleate

 Examples:
Olive oil, corn oil, sesame oil, almond oil, poppy seed oil, soya
oil, castor oil
…
Solvent Use
Esters, such as ethyl These are used as a vehicle in certain intramuscular
oleate, benzyl injections
benzoate and ethyl
ethanoate

Dimethyl sulfoxide Used as a carrier for idoxuridine for topical application to

the skin

Glycofurol Used as a co-solvent in parenteral solutions for

intramuscular or intravenous injections

Ethyl ether Used as a co-solvent with ethanol in collodions