SOLUTIONS

SOLUTIONS
A solution is a homogenous one-phase system
consisting of two or more components.
Solution consists of two phases:
- Solvent phase;
determine the phase of the solution and usually
constitutes the largest proportion of the system,
but there are some exceptions e.g. syrup.
- Solute phase;
dispersed as molecules or ions throughout the
solvent i.e. they are said to be dissolved in the
solvent.


Solutions
Gas in gas (air) solid in solid (alloys) liquid in liquid (alcohol in water)

Gas in liquid (cokes) solid in liquid (sugar in water)
Solutions

Well-mixed (uniform) single phase

homogenous

transparent

cannot be separated by filter

do not separate on standing
sugar in water
Definitions
SOLUBILITY
- It is the number of parts of solvent (by volume)
that will dissolve one part of solute (by weight of
a solid or liquid).
- It also can be defined as the amount of a solute
that passes into solution
- A solute will dissolve best in a solvent that has a
similar polarity to itself.

MISCIBILITY
when the two components forming a solution are
either both gases, solids or liquids it is more usual
to talk in terms of miscibility rather than solubility.

Solutions
Solvent: greater quantity (water)

Solute: smaller quantity (sugar)
Immiscible: two liquids do not mix
miscible: two liquids can mix
e.g. alcohol in water
(in any quantities)
ADVANTAGES OF SOLUTIONS
Liquids are easier to swallow, and so more
acceptable by paediatric and geriatric use.
Faster therapeutic response.
Uniform distribution of drug throughout the
preparation, compared to suspension and
emulsion.
Reduced irritation to the gastric mucosa,
compared to solid dosage forms, due to
immediate dilution by gastric contents.
DISADVANTAGES OF SOLUTIONS
Bulky, so inconvenient to transport and store
If the container breaks, the whole product is
lost.
Poor stability.
Microbial contamination is more likely.
In-accurate dosing.
Difficult to mask the bitter taste of some
drugs.
Most solutions prepared in the pharmacy are
straightforward; others have special problems
associated with them.

All require some knowledge of the solubility
characteristics of the drug(s) being dissolved
(These may be found in Remington's
Pharmaceutical Sciences, dispensing textbooks,
Merck's Index).

Pharmaceutical solutions can be (1) simple or (2)
complex.
In addition that one may find multiple solids (drugs,
stabilizers, buffers, colors, etc.) mixed with multiple
liquids (water, flavors, alcohol, propylene glycol).

Solutions are sometimes classified as:
simple solutions
solutions prepared by chemical reaction.
There is no fundamental differences between
them, these terms refer to the method required
to prepare them.
As an example, salt dissolved in water is a
simple solution.
In contrast, one can prepare Calcium Hydroxide
solution (sometimes called Lime Water) by
adding Calcium Oxide to water.

That which went in is not that which comes out;
a chemical reaction has taken place.
Strong Iodine Solution U.S.P. (Lugols solution)
R/
Iodine 50 gm
Potassium iodide 100 gm
purified water ad 1000 ml
Iodine dissolves in potassium iodide to
form the water soluble I
3
complex

FORMULATION OF SOLUTIONS

A. Aqueous solution
B. Non aqueous solution
AQUEOUS SOLUTION

A. Aqueous solution

Water is the most widely used solvent.
Advantages
Lack of toxicity
non-expensive
physiological compatibility
Disadvantages
Some hydrolysable drugs such as glycosides and
esters form unstable solutions when dissolved in
water.





TYPES OF WATER
1. Potable Water:
Water freshly drawn from the public water
supply (main system) and suitable for drinking.

2. Pharmacopeal Purified Water BP:
- Freshly boiled and cooled immediately before
use to destroy micro-organism.
- Must be used when the presence of salts is
undesirable.
- Prepared by distillation or deionization.



TYPES OF WATER
3. Water For Injections
Sterilized (pyrogen-free) distilled water
used for parenteral solutions.

CO
2
-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.
TYPES OF WATER
Aromatic waters
Aromatic waters
Aromatic waters are saturated solutions of
aromatic or volatile substances in water.
They possess an odor similar to the plant or
volatile substance from which they are made
Due to their pleasant odor, they used as
flavoring or perfuming vehicles in certain
pharmaceutical preparations.
Mostly they exert no therapeutic action.
Examples: peppermint water, chloroform water,
camphor water,..


Concentrated Aromatic Water (Spirits)
These are strong stock solution of aromatic
materials in alcohol.
Fresh aromatic water are prepared by dilution of
the strong one; 1 part of strong solution to 39
parts of water (freshly boiled and cooled).
On dilution they yield a fine precipitate. In the
finally divided form, the precipitated substance is
more easily dissolved in water.

IMPROVEMENT OF AQUEOUS SOLUBILITY
(1) COSOLVENCY
The solubility of poorly soluble drugs can be
improved by the addition of water miscible
solvent in which the compound is soluble.
Vehicles used in combination to increase the
solubility of a drug are called COSOLVENTS.
Most commonly used blends is water/ethanol
blend, other suitable solvents are glycerol,
propylene glycol.
R/
Sodium Chloride 2.0 G.
Menthol .100 G.
Alcohol 10 mL.
Water q.s. ad 30 G.

Sodium chloride is more soluble in water, menthol is
more soluble in alcohol. That is the way they should be
dissolved, and then the two solutions should be mixed
together.
IMPROVEMENT OF AQUEOUS SOLUBILITY
(2) pH Control:
If the drug is a weak acid or weak base, its solubility in
water can be controlled by the pH of the system.
(3) Particle size control:
As particle size decrease the drug solubility increased.
(4) Chemical modification:
The drug may be chemically modified to produce a water
soluble derivative (usually salt form).
Examples;
- sodium phosphate salt of hydrocortisone


NON-AQUEOUS SOLUTIONS

Non-aqueous solutions
If the drug is insoluble (griseofulvin) or
unstable (e.g methylpenicillin) in aqueous
systems, it is necessary to use alternative
systems such as oils, alcohols, liquid
paraffin, glycerol.

Non-aqueous solvents
1. Fixed oil of vegetable origin
- such as olive oil, almond oil, castor oil, ..
- They are used mainly in preparation of
intramuscular injections e.g. Oily Phenol Injection
BP and Calciferol Injection BP, for depot therapy
- Some are of suitable taste and odour for oral use as
solvent for materials as vitamin A and D.
- Oils are unpleasant to use externally, unless in
emulsion.
Non-aqueous solvents
(2) Alcohols
Ethyl alcohol is a widely used solvent, specially
for external use due to its rapid evaporation and
cooling effect (e.g. paints and liniments).
It can be used orally as cosolvent (e.g. elixirs)
Isopropyl alcohol, has similar properties to ethyl
alcohol, but less likely to be abused if taken
orally.
Non-aqueous solvents
(3) Miscellaneous
Glycerol,
dimethylsulfoxide,
liquid paraffin,
propylene glycols,
tinctures.
Types of Preparations
Solutions for cutaneous application;
Lotion, liniments, paints, collodions
Ear (otic) prepartions:
- Simple solution of drugs in either water,
glycerol, alcohol/water mixture for local use
- Applied as drops, sprays or washes
Eye preparations:
These are small-volume sterile liquids to be
instilled on to the eyeball for local effect

Types of Preparations
Irrigations:
- Sterile, large-volume, aqueous solutions for
cleansing of body cavities and wounds.
Mouthwashes and gargles:
- Aqueous solution for the prevention and
treatment of mouth and throat infection can
contain antiseptic and analgesic drugs
Nasal products:
- pH should be adjusted to 6.8.
- Anti-inflammatory and decongestants are
commonly used

Types of Preparations
Oral liquids:
Elixir, linctuses, mixtures and draughts.
Parentral products:
Sterile solution for injection or infusion into the
body.
Rectal preparations:
- Aqueous or oily preparations for cleansing,
diagnosis or therapeutic reasons (e.g.ENEMAS)
Types of Preparations
Intermediate products:
1- Aromatic water and spirites
2- Extracts, infusion and tinctures:
Are concentrated solutions of active
principles from animal or vegetable source.
3- Syrups
-Are concentrated solution of sucrose to
which drug and flavorings are added.
e.g. Codiene Phosphate syrup (cough
suppressant)

RECOMMENDATIONS ON PREPARING SOLUTIONS
1. Small quantities of highly soluble materials
dissolve immediately; solution rate slows down as
more and more solute is added and may stop as
"saturation"' is reached.
2. The more rapid the stirring, the more rapidly
solution is achieved (because turbulence reduces
the width of the '"diffusion layer" around the
particles of solute).
There are some situations when vigorous stirring is
not desirable e.g. foaming agent (as soap), or
viscous solution (formation of air bubbles which
could take many, many hours to go away.
RECOMMENDATIONS ON PREPARING SOLUTIONS
3. Particle size reduction by grinding in a mortar
with a pestle, this is important for "slightly
soluble drug.
4. Heating usually hastens solution rate--but
should be used only when necessary, avoided in
volatile materials.
5. The '"Order of Addition" may be important.
Make certain that you are familiar with the
solubility characteristics of your solutes and
solvents.
6. As a general rule, non-viscous solutions
should be filtered. This rule is not followed when
the volume is small since significant amounts of
the liquid may be retained by the filter paper.
SOLUTION
Solute
Examples of
solutions
Gas Liquid Solid
Gas
Oxygen and other
gases in nitrogen (air)

Liquid
Carbon dioxide in
water (carbonated
water)
Ethanol (common
alcohol) in water;
various hydrocarbons
in each other
(petroleum)
Sucrose (table sugar) in
water; sodium chloride
(table salt) in water;
gold in mercury,
forming an amalgam
Solvent
Solid
Hydrogen dissolves
rather well in metals;
platinum has been
studied as a storage
medium.
Hexane in paraffin
wax, mercury in gold.
Steel, duralumin, other
metal alloys