By Mahfooz Ul Hassan

3. SOLVENT USE IN PHARMACEUTICAL
PREPARATIONS

4. Prepared By:
Mahfooz Ul Hassan
Hajvery University Lahore
Submitted To:
Mam Eesha Tahir Bhatty

5. A WELL-EQUIPPED MEDICINE CABINET STARTS WITH
SOLVENTS.
Solvents are used in hundreds of pharmaceutical
products, many of which are found in our homes. In fact,
some of the products found in our medicine cabinets are
solvents, such as rubbing alcohol. Solvents can play a key
role in our well-being, and they also frequently play a role at
the start of the pharmaceutical manufacturing process.
Isopropyl alcohol, or rubbing alcohol, is an example of
a solvent that plays a dual role. A versatile solvent, it is often
used in our homes as a disinfectant, and is also used as an
industrial solvent to dissolve products such as oils and resins
in manufacturing processes. Additionally, it can be used as a
building block to make other products.

6. SOLVENT USE AS AN ACTIVE INGREDIENTS IN
PHARMACEUTICAL PREPARATIONS
Ointments and other topical products, such as
antibacterial creams and corticosteroids, often use
solvents in the beginning of the process to
manufacture the active ingredients. As the drug is
being transformed into its final form, whether
cream, lotion or liquid, solvents are used as a
medium for blending materials. Solvents also are
used to help the final product achieve the proper
consistency.

7. SOLVENTS USE IN HOUSEHOLDS
Other pharmaceutical items in our households
that use solvents include pet care products.
Solvents are often found in pet shampoos,
ointments, oral medications and topicals. Pet
shampoos use solvents to dissolve a drug for
topical treatment, or to provide moisture and
softeners for our pets’ skin and hair.

8. HOW SOLVENTS WORK IN PHARMACEUTICALS
Solvents can serve one or more functions
in pharmaceutical manufacture. They provide
molecules to build some drugs. For other drugs,
solvents are used for extraction and purification.
Solvents also can provide a reaction medium.
Solvents work in a variety of ways to
contribute to many of the medicines people use
today. As helpers in the formulation of many health
care products such as penicillin, aspirin, cough
syrup, and topical ointments, solvents play an
important role in the medicine cabinet.

9. WHAT IS A SOLVENT?
Solvents are chemical substances that can
dissolve, suspend or extract other materials usually
without chemically changing either the solvents or
the other materials. Solvents can be
organic, meaning the solvent contains carbon as
part of its makeup, or inorganic, meaning the
solvent does not contain carbon.
For example, “rubbing” alcohol is an organic
solvent and water is an inorganic solvent.
Hydrocarbon and oxygenated solvents are
examples of types of organic solvents that can
effectively dissolve many materials.

10. PROPERTIES OF SOLVENTS USE FOR
PHARMACEUTICAL USE:
 Solvents for pharmaceutical use should have this
properties:
1. Should be non-toxic.
2. Should be stable.
3. Should be not highly volatile (stable)??
Because if was volatile will evaporate &leaving
concentrate solution.
Note: the solvent that used in pharmacy is not mean
that it is used orally .it may be used for clarification
of drugs, for isolation or extraction from crude
drug or for cosmetic.

11. WHY DO WE NEED CERTAIN REGULATIONS TO
LIMIT THE USE OF SOLVENTS.
a. Toxicity
b. Odor and taste(obviously not good drug attributes
for both manufacturers and patient.

12. USES OF SOLVENT IN PHARMACEUTICAL
PREPARATIONS;
1. Synthesis of active pharmaceutical ingredients.
2. In formulation.
3. Cleaning the equipments.
4. In separation and purification.
5. As a reaction media
6. In separation and purification.
Steps involved in chemical synthesis of API
1. Reaction
2. Separation and Extraction
3. Purification
4. Drying

13. TYPES OF SOLVENTS FOR PHARMACEUTICAL
USE :
1) Purified water:
It has a solvent effect on most
substances, Purified water is water that is
mechanically filtered or processed to be cleaned
for consumption. Distilled water and deionized (DI)
water have been the most common forms of
purified water and it contains vary amounts of in-
organic salts usually Na,K,Ca+2, iron, Mg, Cl ,
sulfate and bicarbonate.
It is used in preparation of all medication
containing water except non - parenteral solutions
& some official external preparations such as
liniments.

14. 1-It has the widest range of usefulness of all the
solvents employed in pharmaceutical dispensing
&manufacturing.
2-It is a good solvent for most inorganic salts &for
many organic compounds.
3-It is miscibility with other solvents such as alcohol &
glycerin make it useful vehicle for many
pharmaceutical preparations.
* Tap (drinking) water is not normally used for
the manufacture of pharmaceutical solutions or for
extemporaneous compounding, as it contains
dissolved substances.

15. It can interfere with the formulation, for example,
reduce drug solubility and stability ((signs of
incompatibility, such as precipitation, discoloration and
occasion ally effervescence).
Advantages of water:
1- Tasteless &physiological compatibility.
2- Freedom from irritating qualities.
3- Lack of pharmacologic activity& toxicity.
Disadvantages:
1- Favorable medium for many chemical reactions
. 2- Support growth of microorganisms when
contaminated.
3- In pure form add cost to production.

16. HOW TO PURIFY THE WATER??
• Tap (drinking) water is not normally used for the
manufacture of pharmaceutical solutions or for
extemporaneous compounding, as it contains
dissolved substances which could interfere with the
formulation, for example, reduce drug solubility and
stability ((signs of incompatibility, such as
precipitation, discoloration and occasionally
effervescence).
• * D.W. subjects to "distillation" so as to remove
salts of Ca and Mg from it, and hence it is called
D.W.

17.  Water can be purified by other processes including
Reverse osmosis, carbon filtration, microfiltration,
ultrafiltration, ultraviolet oxidation and electro
dialysis.
 Deionization method possesses a number of
advantages as compared to distillation process:
1- Elimination of the use of heat.
2- simple equipment
3- Lower cost.
4- Easy of production &storage.

18. In the deionization method, we used the
exchangers which are synthetic polymeric resins of
high molecular weight in soluble in water & high
content of free amino, sulfonic acid or phenolic
functions.
Polymeric resins are of two types:
 Cationic resins
 Anionic reasons

19. USP DIVIDED WATERS DEPENDING UPON THE
DEGREE OF PURITY INTO:
A- Purified water (D.W)
B-Water USP or drinking water: it is allowed to use In :
 Washing &extraction of a crude drugs.
 Preparation of product for external use.
 In other preparations in which the difference between
water & purified water (D.W) is of no effect.
Water USP is not suitable for general
pharmaceutical use?? Because of the considerable amount
of dissolved solid present.

20. If we compared between water &purified water
100ml water after evaporation &drying yields about
100mg of residue, while , 100ml purified water after
evaporation &drying yields not more than 1mg of
residue .
These residues are the dissolved solids in water
so the only difference between water &purified
water is in the amount of total dissolved solids
(chloride, sulfate, bicarbonate of sodium,
potassium, calcium & magnesium). Water is clear,
colorless & odorless. It's PH is neutral.

21. C- Water for injection:
This is a pyrogen free water purified by
distillation. it is used for preparation of products for
parenteral use (intravenous, intramuscular).it is
intended for use as a solvent only in solution that
are to be sterilized after preparation. It contains no
added substances &meets the requirement of the
tests (pyrogen test) for purified water.
D-Sterile water for injection:
It is water for injection sterilized &packaged in a
suitable single dose container of glass type of not
larger than 1000ml size.

22. The preparation must meet the requirement of
sterility test & the pyrogen test.
E-Bacteriostatic water for injection:
this is sterilized water for injection containing
Bacteriostatic agent, it may package in a single
dose container not larger than 5ml size &in
multidose of not larger than 30ml.
F-CO2-free water:
For formulation of solutions of some drugs (e.g.
aminophylline), it must be free from carbon dioxide.
This is obtained by boiling distilled water for 10
minutes, cooled and sealed in their containers and
then sterilized.

23. G-Sterile water for inhalation:
Is prepared from water for injections that is
sterilized and suitably packaged. It contains no anti-
microbial agents, except when used in humidifiers
or similar devices and when liable contamination
over a period of time or other added substances.
Note: do not use sterile water for inhalation for
Parentral administration

24. H- Sterile water for irrigation:
Sterile Water for Irrigation USP is a sterile,
hypotonic, non- pyrogenic irrigating fluid or
pharmaceutical aid (solvent) entirely composed of
Sterile Water for Injection USP. It is prepared by
distillation and contains no antimicrobial or
Bacteriostatic agents or added buffers. The pH is
5.7. ((Irrigation means washing, such as washing
an organ after a certain surgery (operation)

25. 2) ALCOHOL USP: SUCH AS ETHYL ALCOHOL,
ETHANOL, C2H5OH:
1- Alcohol is next to water is the most useful solvent.
2-it is a good solvent for many organic subs. both
natural &synthetic.
3-it is dissolve important plant constituents such as
resins, volatile oils, alkaloids, glycosides &neutral
principles.
4- Together with water it forms hydro-alcoholic
solvent which dissolves both water soluble and
alcohol soluble subs. and to extract active
constituents from crud drug.
5- Dehydrated alcohol USP (absolute alcohol)
contains not less than (99.5%)

26. 6-Alcohol has advantages over the water; it is not
subjected to deterioration (growth of
microorganisms). ((Used in liquid products as an
antimicrobial preservative alone or with other
agents)).
7- Alcohol is frequently used with other solvents such
as glycols & glycerin to reduce the amount of
alcohol required.
8-It is used for OTC oral products intended for
children under (6 years), the recommended alcohol
contains limit for product is over: (0.5%) for children
under (6 years), (5%) for children (6-12 years), (10
%) for over 12 years.

27. 3) DILUTED ALCOHOL (NF):
It is prepared by mixing equals volumes of
alcohol USP with 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 so the final volume
is generally about 3% less than would be expected.
Diluted alcohol is a useful hydro alcoholic solvent in
various pharmaceutical processes and preparation.

28. 4) ISOPROPYL ALCOHOL:
It is about 70% by volume Isopropyl alcohol, the
remaining consisting of water with or without color
additives ,stabilizers & perfume oils .it is used
externally as a rubefacient & soothing rub & as a
vehicle for topical products. This preparation is 91%
isopropyl alcohol solution is commonly used by
diabetic patients in preparing needles & syringes for
subcutaneous injections of insulin & for disinfecting
the skin. Also Used as solvent in cosmetic and
dermatologic preparations.

29. 5) GLYCERIN USP (GLYCEROL):
1-It's clear liquid with sweet taste.
2- It is miscible with both water and alcohol but not
with ether and chloroform.
3- As a solvent it is viscous, therefore solute is slowly
soluble in it, unless it is render to less viscosity by
"heating".
4-Glycerin has preservative stabilizer property.
5- It is used in many internally preparations
(suppository) and ear drops because it softens the
wax found in the ear.

30. 6) PROPYLENE GLYCOL USP:
Viscous liquid miscible with water and alcohol
in all proportion and is soluble in ether, acetone and
chloroform.
It is useful solvent with a wide range of
applications and is frequently substituted with
glycerin in modern pharmaceutical& cosmetic
preparations.

31. 7) POLY ETHYLENE GLYCOL 400:
1-it is miscible with water, acetone, alcohol & other
glycols.
2-it dissolves many water–soluble organic
compounds & certain water soluble subs. Such as
acetyl salicylic acid & theophylline.

32. 8) KETONE
There are only two official solvent-vehicles in the
ketone group.
1. Acetone
2. Methyl iso Butyl Ketone
Methyl ethyl ketone is not an official substance, But
according to the section of USP it is used as a
solvent for assays, tests and processing.
Why we not use ketone officially?
Officially ketone have limited usefulness because
of their; Volatility, flammability and toxicity. They
do have some unique solvent properties which
make them useful.

33. It is miscible with water, alcohol, ether,
chloroform and in most of the oils.
Precaution:
It is stored in tight containers and stored remote
from fire.

34. OILS
Some special vegetables and essential oils used
primarily as flavors and scents.
 The National Formulary section of USP-NF has
monographs for various oils of this type such as;
 Anise oil, Lemon oil and Rose oil.
 Insoluble in water, miscible in mineral oil, slightly
soluble in alcohol and soluble in other fixed oils,
chloroform, and ether.

35. BOLING POINTS OF SOLVENTS
An important property of the solvents is the boiling
point. This is also determines the speed of
evaporation.
Small amounts of low boiling- points solvent
like diethyl ether , dichloromethane or acetone will
evaporate in seconds at room temperature, while
high-boiling point solvents like water or diethyl
sulphoxide need higher temperatures, an air flow,
or the application of vacuum for fast evaporation.
 Low boilers: Boiling point below 100°C.
 Medium boilers: Below 100°C and 150°C.
 Higher boilers: Above150°C.

36. DENSITY
Most organic solvents used in pharmaceutical
preparations have a lower density than water;
which means they are lighter and will form a
separate layer on the top of water.
Exception:
Most of the halogenated solvents like
dichloromethane and chloroform will sink to the
bottom of the container, leaving water as the top
layer.
This is important to remember when
partitioning compounds between solvents and
water in a separately funnel during chemical
synthesis.

37. Often specific gravity is cited in place of density.
Specific gravity is defined as ;
“Density of the solvent dived by density of
water as the same temperature”.
As specific gravity is a unit less property, it
readlly communicates weather a water is insoluble
solvent will float (SG≥1.0) or sink with water.