Pharmaceutical Technology

Lec : 4 Dr.Hussam

Solvents 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.
What is the difference Between Liquid and Aqueous??
 Liquid is a state of matter that has no fixed shape but has a
definite volume. An aqueous solution is a solution in which a
substance is dissolved in water.
 All aqueous solutions are liquids, but not all liquids are aqueous
solutions.
 Liquid must contain water molecules while aqueous there is no
need to be containing water molecules, it is may be alcohol or
other aqueous solutions.

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 ,
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sulfate and bicarbonate. It is used in preparation of all medication
containing water except non-parenteral solutions & some official
external preparations such as liniments. Freshly D.W has PH about
5.6 &usually changes to 6 on storage.
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 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.
 Water can be purified by other processes including Reverse
osmosis, carbon filtration, microfiltration, ultrafiltration,
ultraviolet oxidation and electrodialysis..
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.

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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. These resins are mainly of two types:
1- Cation or acid exchangers which permit the replacement of cations
in solution with hydrogen ion.
2- Anion or base exchangers which permit the removal of anions.
The manner in which these resins function as follows:
1-Acid or cation step: in which the cation of the salt are replaced with
H+ ions. The cations so replaced remain behind fixed to the resin.
H-resin + M+ (Cation ,Na+) +X- (Anion, Cl-)  M+-resin +H+ + X-

2-Base or anion exchange step: in which the water is passed through a

basic resin usually a polymeric &the anion remaining after step1 is
removed according to this reaction:

Resin-NH2 + H+ +X-  Resin-NH2HX

 The important solvent for pharmaceutical solutions is water.

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.

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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. 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.

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.

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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: 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))).

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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%).
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 would be expected. Diluted alcohol is a useful hydroalcoholic
solvent in various pharmaceutical processes and preparations.

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4) Isopropyl alcohol: 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.

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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.