solvents used in pharmaceutical preparations

3. CONTENTS:
 Introduction (Solvent)
 Purify Water (USP)
 Dehydrated Alcohol (USP)
 Alcohol (USP)
 Glycerin (USP)
 Propylene Glycol
 Isopropyl Rubbing Alcohol

4. WHAT IS 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 organic, meaning
the solvent does not contain carbon

5. EXAMPLE:
 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.
On What Grounds We Choose Solvent:
 Solubility
 Stability
 Bioavailability
 Therapeutic Effect

6. SOLVENTS USED IN PHA R MA CEUTICA L
PR EPA RA TIONS:
 There are several solvents which are
excessively used in the pharmaceutical
preparations. Some are discussed below:
1. Purified Water (USP):
 It is defined, when evaporated to dryness it
must not yield more than 0.001% of residue.
(0.001% residue means 1mg if solids per
100ml of water).

7. PURIFIED WATER:
 While, for drinking water the percentage is 1% of residue. But this not used in pharmaceutical
preparations. It is used in some other process i.e. extraction or washing of apparatus.
 The Naturally occurring water can’t be used in any way or process.
 Uses
 Its use is permitted in washing, in extraction of crude vegetable drugs, in
preparation of certain products for external use, and when the difference between
tap water and purified water is of no consequence.
 Purified Water, USP, is intended for use in the preparation of aqueous dosage
forms except those intended for parenteral administration (injections).

8. WATER FOR PHARMACEUTICAL
PREPARATIONS:
 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.
 Signs of such incompatibilities are precipitation, discoloration, and occasionally
effervescence.
 Purified Water, USP, has fewer solid impurities than ordinary drinking water.

9. M E T H O D S O F M A K I N G P U R I F I E D WA T E R :
 There are 3 methods:
1. Distillation
2. Ion Exchange method
3. Reverse Osmosis

10. 1. DISTILLATION:
 Many stills in various sizes and styles with capacities ranging from about 0.5 to 100
gallons of distillate per hour are available to prepare purified water.
 Generally, the first portion of aqueous distillate (about the first 10% to 20%) must be
discarded because it contains many foreign volatile substances usually found in urban drinking
water, the usual starting material.
 Also, 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 because
distillation to dryness would undoubtedly result in decomposition of the remaining solid
impurities to volatile substances that would distill and contaminate the previously collected
portion of distillate.

12. 2. IONIC EXCHA NGE METHOD:
 Equipment passes water through a column of cation and anion exchangers
consisting of water insoluble synthetic, polymerized, phenolic, carboxylic, and amino
or sulphonated resins of high molecular weight. These resins are mainly of two
types;
a) Cationic : The cation or acid exchangers which permits the exchange of the
cations in solution (tap water) with hydrogen ion from the resin. H-resin + M+ +
X+H2O M-resin + H+ + X- + H2O(pure)
b) Anionic : The anion or Base Exchange resins which permit the removal of
anions. Resin-NH2 + H+ + X- + H2O Resin-NH2 .HX + H2O (pure)

14. 3. REVERSE OSMOSIS:
 It is the reverse of the normal osmosis. It is defined as,“ the movement of water
molecules from a region of low concentration to a region of high concentration through
filters (semipermeable membranes).” The process is also called Cross Flow Membrane.
In this process water is mechanically pumped through the filter from a region of high
concentration to region of low concentration.
 It is the modern and the best method of making purified water. With the help of this
process we can remove the particles having size of about 0.001 µm or even smaller. This
process removes almost all kind of impurities and even the microscopic germs i.e.
pyrogens, bacteria, organic molecules and 90-99 % ions.

16. TYPES OF WATER:
 Non-potable
 Potable (drinkable) water
 USP purified water
 USP water for injection (WFI)
 USP sterile water for injection
 LUSP sterile water for inhalation
 USP bacteriostatic water for injection
 USP sterile water for irrigation

19. 2. DEHYDRATED ALCOHOL(USP):
 The Dehydrated Alcohol is also used as commercial solvent for few
pharmaceutical preparations. According to United State Pharmacopoeia,
“Dehydrated Alcohol is that Alcohol which contain not less than 99.5% Ethyl
alcohol C2H5OH by volume.”
 Uses: Dehydrated Alcohol USP is mostly and excessively used in the
External Tropical Preparations.
 Preserve in tight containers, protected from light.

21. 3. ALCOHOL(USP):
 Definition:
 Alcohol, USP, is 94.9% to 96.0% C2H5OH by volume (i.e., v/v) when
determined at 15.56°C, the U.S. government’s standard temperature for alcohol
determinations Dehydrated Alcohol USP Dehydrated Alcohol USP, contains not
less than 99.5% C2H5OH by volume and is used when an essentially water-free
alcohol is desired.
 Properties:
 It has a characteristic odor and burning taste and is miscible in all proportions
with water, ether or chloroform.

22. • USES:
• Next to water, alcohol is the most useful solvent in pharmacy.
• It is used as a primary solvent for many organic compounds.
• By varying the proportion of the two agents, the active constituents may be
selectively dissolved and extracted or allowed to remain behind, according to their
particular solubility characteristics in the menstruum.
• Alcohol has been well recognized as a solvent and excipient in the formulation
of oral pharmaceutical products.
• Certain drugs are insoluble in water and must be dissolved in an alternative
vehicle.
• Alcohol is often preferred because of its miscibility with water and its ability to
dissolve many water-insoluble ingredients, including drug substances, flavorants, and
antimicrobial preservatives.

23. . USES:
• 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, and other agents.
• Alcohol is employed as a diffusible stimulant, diuretic, diaphoretic and
hypnotic. In well-selected cases, especially in patients accustomed to its use, it
may be very valuable; otherwise it is apt to do more harm than good.

25. RECOMMENDATION FOR USE OF
ALCOHOL IN ORAL
PREPARATIONS:
 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. For OTC oral products
intended
 For children under 6 years of age, the recommended alcohol content limit is
0.5%
 For products intended for children 6 to 12 years of age, the recommended limit
is 5%
 For products recommended for children over 12 years of age and for adults, the
recommended limit is 10%.

26. HYDROALCOHOLIC
SOLVENTS:
 Together with water, it forms a hydroalcoholic mixture that dissolves
both alcohol-soluble and water-soluble substances, a feature especially
useful in the extraction of active constituents from crude drugs.
 It is used as selective solvents (usually active ingredients resins,
alkaloids, glycosides are soluble but many therapeutically inert principles
e.g. gums, album and starch are insoluble which makes it more useful as a
selective solvent.

27. PRECAUTIONS:

28. 4. GLYCERIN(USP):
Glycerin is a clear syrupy liquid with a sweet taste and non-toxic.
It is a viscous and slightly sweet compound producing a smooth,
full vape.
Properties:
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.
It dissolves the fix alkalies in large number of salts, vegetable acids, pepsin, tannins
and some active principles of plants but it also dissolves gums, soluble carbohydrates
and starch.
Glycerin is derived from both natural and petrochemical feed-stocks.

29. USES:
 1. It is also of special value as a simple solvent in phenol glyceride, antipyrine & benzocaine otic
solution. Those preparations in which glycerin is used as primary solvent are called glycerides &
glycerin's.
 2. It is mostly used as co-solvent or auxiliary solvent. It means it is used with some other solvent.
 3. It is used as stabilizer in different preparations for example to increase the viscosity in suspension
or emulsion, or sweetening agent for those preparations in which the dosage is bitter in taste etc.
 4. In high concentrations it has preservative action. It restricts the microbial growth.
 5. It is also used in oral or internal preparations as it is sweet in taste. 6. It dissolves the fixed
alkaloids, a large no. of salts, vegetable acids, pepsins, tannins, and some active principles of plants but it
also dissolve gums soluble carbohydrates & starch

30. PRECAUTION:
Keep in sealed container.
 Keep out of reach of children.
 Use only with adequate ventilation

31. 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 than what would otherwise be expected.
 Thus, when 50 mL of each component is combined, the resulting product measures
approximately 97 mL. It is for this reason that the strength of Diluted Alcohol, NF, is not
exactly half that of the more concentrated alcohol but slightly greater, approximately 49%.
 Diluted alcohol is a useful hydroalcoholic solvent in various pharmaceutical processes
and preparations.

32. 5. PROPYLENE GLYCOL:
 Definition:
Propylene Glycol (PG) USP/EP is a pharmaceutical grade of Monopropylene Glycols
(PG or MPG) with a specified purity greater than 99.8%.
 Description:
Propylene glycol is a viscous liquid.
A relatively nontoxic liquid that is practically colorless, odorless, and tasteless.
 Properties:
It is miscible with water, acetone, chloroform and alcohol in all proportions.
It is soluble in ether and will dissolve many essential oils but is immiscible with fixed
oils.

33.  USES:
 It may be used for internal or for external preparations.
 Propylene glycol USP/EP (pharmaceutical grade) is used as a non-active,
"enabling" agent (excipient).
 It acts as emulsifier in cosmetic and pharmaceutical creams
 It is widely used as a substitute for glycerin.
 It is claimed to be as effect as ethyl alcohol in its power of inhibiting mold
growth and fermentation.
 It is used in oral and topical preparations.

34.  STORAGE:
Propylene Glycol - USP is a high-purity material, which must be handled with
special precautions to avoid contamination.
Under ordinary conditions, mild steel is a satisfactory material of construction;
however, for long-term storage and where iron contamination and color are
objectionable, stainless steel or aluminum vessels are recommended.
Side Effects:
Ingestion of propylene glycol could cause irritation, burning sensations to the throat
and mouth, nausea and vomiting.

35. PRECAUTIONS:
 Use only with adequate ventilation
 Avoid breathing vapor, mist or gas
 Avoid contact with eyes, skin and clothing
 Keep container closed
 Wash thoroughly after handling
 Keep out of reach of children

36. 6. ISOPROPYL RUBBING ALCOHOL:
 Definition:
The United States Pharmacopeia defines 'isopropyl rubbing alcohol USP' as containing
approximately 70 percent by volume of pure isopropyl alcohol and defines 'rubbing
alcohol USP' as containing approximately 70 percent by volume of denatured alcohol.
 Constitution:
Isopropyl rubbing alcohol is about 70% by volume (volume by volume) isopropyl alcohol,
the remainder consisting of water with or without color additives, stabilizers, and perfume
oils.
 Indications:
It is used to relieve muscle stiffness or excessive perspiration.

37.  USES:
 It is used:
o Externally as a rubefacient (A rubefacient is a substance for topical application
that produces redness of the skin e.g. by causing dilation of the capillaries and an
increase in blood circulation) and Soothing rub
o As a vehicle for topical products.
 This preparation and a commercially available 91% isopropyl alcohol solution
are commonly employed by diabetic patients in preparing needles and syringes for
hypodermic injections of insulin and for disinfecting the skin.

38.  PROPERTIES:
 All rubbing alcohols are volatile and flammable.
 They have an extremely bitter taste from additives.
 Naturally colorless, products may contain color additives.
 They may also contain medically-inactive additives for fragrance, such as
wintergreen oil (methyl salicylate), or for other purposes.

39. CAUTIONS/PRECAUTIONS
:
 Cautions:
 For external use only.
 May be poisonous if taken internally.
 Avoid inhalation of vapors.
 Keep out of reach of children.
 Precautions:
 It is unsafe for human consumption (orally).
 Poisoning can occur from ingestion, inhalation, absorption, or consumption of
 rubbing alcohol.
 Keep away from open flames or sparks.

40. III. RUBBING ALCOHOL,
USP
Composition:
 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.
Uses:
 It is also used as a vehicle for topical preparations.
 The use of this denaturant mixture makes the separation of ethyl alcohol from the
 denaturants virtually impossible with ordinary distillation apparatus.
 This discourages the illegal removal for use as a beverage of the alcoholic content of
 rubbing alcohol.
 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.
Precautions:
 The product is volatile and flammable and should be stored in a tight container remote from fire.