In pharmaceutical terms , solutions are

liquid preparations that contain one or

more chemical substances dissolved in a
suitable solvent or mixture of mutually
miscible solvents.
 The maximum concentration to which a
solution may be prepared with that agent and
that solvent . When a solvent at ,a given
temperature , has dissolved all of the solute it
can , it is said to saturated.

 When a solute dissolves , the substance’s

intermolecular forces of attraction must be
overcome by forces of attraction between the
solute and solvent molecules.
 This involves breaking the solute –solute forces
and the solvent –solvent forces to achieve the
solute-solvent attraction.
 “like dissolves like,”  a solvent having a
chemical structure most similar to that of the
intended solute will be most likely to dissolve
it.
 Strong electrolytes (ionizable) and polar
compounds are soluble in water.
 Organic compounds are more soluble in
organic solvents than in water.
Temperature:
Most chemicals absorb heat when they are dissolved and are
said to have a positive heat of solution increased
solubility with an increase in temperature. A few chemicals
have a negative heat of solution and exhibit a decrease in
solubility with a rise in temperature.
pH of the solution:
Many of the important organic medicinal agents are either weak
acids or weak bases, and their solubility depends to a large
measure on the pH of the solvent.
oThe solubility of a weak base (e.g. alkaloids , antihistamines,
local anaesthetics) can be increased by lowering the pH of
its solution.
o The Solubility of a weak acid (e.g. barbiturates and
phenobarbital) is improved by a pH increase.
 Other factors affecting solubility are: chemical and
physical properties of the solute and the solvent,
pressure, and the state of subdivision of the solute
(particle size).
The solubility of a pure chemical substance at a given
temperature and pressure is constant;
Rate of solution the speed at which it dissolves,
depends on:
1. The particle size of the substance  The finer the
powder  the greater the surface area, which comes in
contact with the solvent  the more rapid the
dissolving process
2. The extent of agitation  the greater the agitation, the
more unsaturated solvent passes over the drug and the
faster the formation of the solution.
 1. Co-solvency:
Used for:
weak electrolyte or non-polar compound
Solubility  by:
addition of a water- miscible solvent in which the
compound is also soluble.
Vehicles used in combination to increase the
solubility are called "co solvents".
 2. pH control:
Used for:
weak acid or a weak base
Solubility  by:
 The solubility of a weak base can be
increased by lowering the pH of its solution.
 The Solubility of a weak acid is improved
by a pH increase.
 3. Solubilization:
Used for:
insoluble or poorly soluble drug in water
Solubility  by:
 the addition of a surface active agent

This phenomenon of micellar solubilization has been

widely used for the formulation of solutions.
Solubilisation begins at CMC
 4. Complexation:
Used for:
poorly soluble drug
Solubility  by:
 Interaction of a poorly soluble drug with a soluble
material to form a soluble intermolecular
complex.
 E.g. Complexation with cyclodextrins
  5. chemical modification:
 It’s the production of water soluble derivative of drug
(e.g. water soluble salt)
 Examples:
1. Synthesis of the sodium phosphate salts of
hydrocortisone, prednisolone and betamethasone.
2. Water soluble chloramphenicol sodium succinate has no
antibacterial activity but it is suitable for parenteral
administration as a solution in order to obtain high blood
levels. Then it is converted back to the active base.
 1) Alcohol, USP: Ethyl Alcohol, Ethanol,
C2H5OH :

 Alcohol is the most useful solvent in pharmacy next

to water.
 It is used as primary solvent for many organic
compounds.
 Together with water, it forms a hydroalcoholic
mixture that dissolves both alcohol-soluble and
water- soluble substances  This is especially useful
in the extraction of active constituents from crude
drugs.
 Glycerin is a clear syrupy liquid with a sweet taste.
 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.
 Glycerin has preservative qualities and is often
used as a stabilizer and as an auxiliary solvent
(Cosolvent) in conjunction with water or alcohol.
 It is used in many internal preparations.
 Propylene glycol, a viscous liquid, is miscible with
water and alcohol.
 Used as Cosolvent.
 It is a useful solvent with a wide range of
applications and is frequently substituted for
glycerin in modern pharmaceutical formulations.
 Water is most widely used solvent for use as
vehicle ... why?
 Due to:
1. Lack of toxicity.
2. Physiological compatibility.
3. Ability to dissolve wide range of materials
 Ordinary drinking water from tap is not acceptable for
manufacture of aqueous pharmaceutical
preparations or compounding of prescriptions ....
why??
 Because of chemical incompatibilities
between dissolved solids and medicinal
agents.
 Signs of incompatibilities: precipitation,
discoloration and effervescence.
 Purified water USP: contain fewer solid impurities (when
evaporated to dryness, it must not yield more than
0.001% of residue(1 mg of solid per 100ml of water )).
 Intended for use in preparation of aqueous dosage form
except those intended for parenteral administration
(injections).
 Highly pure, sterile & pyrogen free water.
 The main methods used in the
preparation of purified water

Reverse
Distillation Ion exchange.
osmosis
 Many stills in various sizes and styles with
capacities from 0.5 to 100 gallons of
distillate per hour are available (from 2 to 40
liter/hour).
 The first portion of aqueous distillate (first 10 to
20%) must be discarded ... why?
Since it contains many foreign volatile substances.
 The last portion of water (about 10% of the
original volume of water) remaining in the
distillation apparatus must be discarded ... why?
 Because distillation to dryness result in
decomposition of remaining solid impurities to
volatile substances that will distil and
contaminate the previously collected portion of
distillate.
 Ion exchange equipment passes water
through a column consists of water -
insoluble synthetic polymerized resins of high
molecular weight (organic nature).
 The resins are mainly of 2 types used
successively to remove cations and anions
from water.
 Water purified in this manner referred to as
demineralized or deionized water and may be
used in pharmaceutical preparations calling
for distilled water.
 Advantages over distillation:
 No heat is required.
 Simple equipment.
 Ease of operation.
 Minimal maintenance of the equipment.
Normal Reverse
Osmosis Osmosis
 Why it’s called reverse osmosis?
 In osmosis, the flow through a
semipermeable membrane is from a less
concentrated solution to a more concentrated
solution.
 In reverse osmosis the flow is from the more
concentrated to the less concentrated
solution.
 Reverse osmosis removes all viruses,
bacteria, pyrogens, and organic molecules
and 90% to 99% of ions .