SUBMITTED TO: SIR.

SAJID HUSSAIN
SUBMITTED BY: FAHAD RASHEED
REG #: PHR120192016
SEMESTER: 3rd Pharm-D
ASSIGNMENT: PHARMACEUTICAL SOLVENTS
DATE: 10 Feb, 2021.

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Contents
PHARMACEUTICAL SOLVENTS.................................................................................................................. 3
INTRODUCTION ....................................................................................................................................... 3
SOLVENTS USE IN HOUSEHOLDS: ......................................................................................................... 3
HOW SOLVENTS WORK IN PHARMACEUTICALS: ................................................................................... 3
WHAT IS A SOLVENT? .......................................................................................................................... 3
PROPERTIES OF SOLVENTS USE FOR PHARMACEUTICAL USE: ............................................................... 4
USES OF SOLVENT IN PHARMACEUTICAL PREPARATIONS: ....................................................................... 4
TYPES OF SOLVENTS FOR PHARMACEUTICAL USE: ................................................................................... 5
1) PURIFIED WATER: ................................................................................................................................ 5
Advantages of water:........................................................................................................................... 5
Disadvantages of water: ...................................................................................................................... 5
2) ALCOHOL USP: SUCH AS ETHYL ALCOHOL, ETHANOL, and C2H5OH: ..................................................... 7
3) DILUTED ALCOHOL (NF): ...................................................................................................................... 7
4) ISOPROPYL ALCOHOL:.......................................................................................................................... 8
5) GLYCERIN USP (GLYCEROL): ................................................................................................................. 8
6) PROPYLENE GLYCOL USP: .................................................................................................................... 8
7) POLY ETHYLENE GLYCOL 400: .............................................................................................................. 8
8) KETONE: .............................................................................................................................................. 8
Why we not use ketone officially? ....................................................................................................... 9
OILS ......................................................................................................................................................... 9
BOLING POINTS OF SOLVENTS: ................................................................................................................ 9
DENSITY: ................................................................................................................................................. 9
Bibliography ......................................................................................................................................... 11

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PHARMACEUTICAL SOLVENTS

INTRODUCTION

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.

SOLVENT USE AS AN ACTIVE INGREDIENT 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.

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, and oral medications and topical. Pet
shampoos use solvents to dissolve a drug for topical treatment, or to provide moisture and
softeners for our pet’s skin and hair.

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.

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
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inorganic solvent. Hydrocarbon and oxygenated solvents are examples of types of organic
solvents that can effectively dissolve many materials.

PROPERTIES OF SOLVENTS USE FOR PHARMACEUTICAL USE:

Solvents for pharmaceutical use should have these properties:

 Should be non-toxic.

 Should be stable.

 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.

WHY DO WE NEED CERTAIN REGULATIONS TO LIMIT THE USE OF SOLVENTS?

 Toxicity

 Odor and taste (obviously not good drug attributes for both manufacturers and patient.

USES OF SOLVENT IN PHARMACEUTICAL PREPARATIONS:

 Synthesis of active pharmaceutical ingredients.

 In formulation.

 Cleaning the equipments.

 In separation and purification.

 As a reaction media 6. In separation and purification.

Steps involved in chemical synthesis of API :

 Reaction

 Separation and Extraction

 Purification 4. Drying

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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.

 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.

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:

 Tasteless &physiological compatibility.

 Freedom from irritating qualities.

 Lack of pharmacologic activity& toxicity.

Disadvantages of water:

 Favorable medium for many chemical reactions.

 Support growth of microorganisms when contaminated.

 In pure form add cost to production.

USP DIVIDED WATERS DEPENDING UPON THE DEGREE OF PURITY INTO:

A- Purified water (D.W):

B-Water USP or drinking water:

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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.

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. Its PH is neutral.

C- Water for injection:

This is 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.

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.

G-Sterile water for inhalation:

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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 parenteral administration.

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)

2) ALCOHOL USP: SUCH AS ETHYL ALCOHOL, ETHANOL, and

C2H5OH:
 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%)

 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.

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

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would be expected. Diluted alcohol is a useful hydro alcoholic solvent in various pharmaceutical
processes and preparation.

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.

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.

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.

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.

8) KETONE:
There are only two official solvent-vehicles in the ketone group.

1. Acetone

2. Methyl iso Butyl Ketone

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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.

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.

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.

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.

 Higher boilers: Above150°C.

 Medium boilers: Below 100°C and 150°C.

 Low boilers: Boiling point below 100°C.

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:

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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.

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 readily communicates weather a water is insoluble
solvent will float (SG≥1.0) or sink with water.

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Bibliography

Basicmedicalkey. (2016, June 01). Retrieved Feb 10, 2021, from Basicmedicalkey:
https://basicmedicalkey.com/15-pharmaceutical-solvents-and-solubilizing-agents/

researchgate.net. (2010, January 15). Organic solvents in the pharmaceutical industry. Retrieved Feb 10,
2021, from researchgate.net:
https://www.researchgate.net/publication/41823466_Organic_solvents_in_the_pharmaceutical_indust
ry

slideshare.net. (2019, January 27). Solvent use in pharmaceutical. Retrieved Feb 10, 2021, from
slideshare.net: https://www.slideshare.net/MahfoozUL/solvent-use-in-pharmaceutical

solvents.americanchemistry. (2004, April 13). Solvents for Pharmaceutical Manufacturing. Retrieved Feb
10, 2021, from solvents.americanchemistry: https://solvents.americanchemistry.com/Pharmaceuticals/

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