Solution

3rd stage /first semester

ANSEL'S Pharmaceutical
Dosage Forms and Drug
Delivery Systems ELEVENTH EDITION Dr. Haithem
 Dispersion types
 Dispersion (dispersed system) is a mixtures of two
substances, one of which (dispersed phase) is distributed in
form of subdivided particles throughout another substance
(dispersion medium).
 Classification of dispersed systems:
Molecular dispersions
 Molecular dispersion is a true solutions. The dispersed phase
(solute) is in form of separate molecules homogeneously
distributed throughout the dispersion medium(solvent). The
molecule size is less than 1 nm. Example of molecular
dispersions is aqueous solutions of salts.
 Dispersed types
Colloids
 Colloids are micro-heterogeneous dispersed systems, in which
the size of the dispersed phase particles is within the range 1 -
1000 nm (i.e. ≤ 1µm) The colloids phases can not be separated
under gravity, centrifugal or other forces. Dispersed phase of
colloids may be separated from the dispersion medium by
micro-filtration. Example is emulsions.
Coarse dispersions
Coarse dispersions are heterogeneous dispersed systems, in
which the dispersed phase particles are larger than 1 µm.
For example: suspensions.
solutions
 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“.
Types of solutions
Solution of liquid in liquid
such as(alcohol in water)

Solution of gas in liquid such

as (solution of ammonia)

Solution of solid in liquid

such as NaCl in water
1- Solution of liquid in liquid
 When two liquids such as water/alcohol are
mixed a homogenous system is formed
irrespective of the proportions (miscible)
 When phenol /water are mixed a

homogenous system only formed when

mixed in a certain proportion (miscible in
certain proportion).
 When mineral oil /water are mixed no system

is formed when mixed at any proportion

(immiscible).
2- Solution of solid in liquid
 Most of true solutions are example of solid in
liquid solution.
 Example is a solution of NaCl in water.
3- Solution of gas in liquid

 The solubility of gas in liquid is

described by Henry,s Law which state
that the solubility of gas is very nearly
proportional to the pressure if the
temperature remain constant
provided that the gas is only slightly
soluble.
 
Effect of temperature on solubility of
gas:
 Increase the temperature lead to
decrease the solubility, e.g CO2 is twice
as soluble 0 oC as it at 20 oC.
 
Note: When a salt is added to a liquid containing
dissolved gas, liberation of gas occurs due to the
Effect of pressure on the
decrease solubility (salting out of the gas). solubility of gases.
Classification of solutions according to
its Therapeutic use

oral

Vaginal parenteral
, rectal
Otic and
nasal

Ophthalmic
Ophthalmic topical
Classification of solutions according to
their composition
1. Syrups (Aqueous solution containing sugar).
2. Elixer (sweetened hydroalcoholic solution).
3. Spirits (solution of aromatic material with
alcohol solvent).
4. Aromatic water (solution of aromatic
material in water as solvent).
5. Tinctures or fluid extract (prepared by
extracting active constituent from crude
drug).
Classifications of solutions according to the
procedure of preparation
1. Solutions prepared by simple solution method
2. Solution prepared by chemical reactions
3. Solution prepared by simple solution with
sterilizations such as ophthalmic solution,
anticoagulant ,irrigating solution , physiological
solution and I.V fluids.
4. Solution prepared by extraction (tincture of
cardamon).
1-Solution prepared by simple solution
   easiest and simplest method of preparation.
 The
 If a solution could be prepared by simple solution and by
chemical reaction, then simple solution is preferred.
Some substances can form solution by both simple
solution and chemical reaction. For example Ca(OH)2
solution which known as lime water is prepared according
to simple solution by dissolving Ca(OH)2 in water and by
chemical reaction by shaking lime CaO with an excess of
water as shown in Equation below
2-Solution prepared by chemical reaction
chemical reaction involves using many reagents
resulting in many compounds hard to be purified. It
contains all the products of the reaction that have taken
place during the method of preparation.
Although simple solution is preferred, sometimes
chemical reaction has to be chosen for the following
reasons:

1. The pure solute may not dissolve from a solid state in

other way than chemical reaction. E.g. Aluminum
subacetate
2. The active constituent is not obtained or not
readily usable in a form other than that of
solution e.g. formaldehyde solution (active
constituent is gas) and hydrogen peroxide

3. Some by products are desired like Mg citrate,

which is used as cathartic.
3-Solution prepared by extraction
 Certain pharmaceutical preparations are prepared by
extraction, that is, by withdrawal of desired
constituents from crude drugs through the use of
selected solvents in which the desired constituents are
soluble.
Example extract solution of ipecac and tincture of
tolu.
4-Solution prepared by simple solution with
sterilization
 Anti-coagulants:
 1. Heparin solution USP sterile solution of 75,000

units of heparin in sodium chloride injection.

 2. Citrate, phosphate, dextrose solution: it is

sterile solution consist from 3% citric acid, 26.3%

sodium citrate, 2.22% sodium bi-phosphate and
25.5% dextrose.
 Irrigating solution: it is used to flush or bathe

wounds or surgical tissues, should be sterilized

because it is used for sensitive areas of the body.
solubility
The solubility of an agent in a particular solvent
indicates the maximum concentration to which a
solution may be prepared with that agent and that
solvent (solubility)
When excess of solid (solute) is shaken with liquid
(solvent) for a period of time a maximum amount of it
will be dissolved (saturated solubility).
When excess amount of solute is added to a
saturated solution and the temperature is increased,
more of solute will be dissolved (super saturated
solution).
Factors affecting solubility
Tempreture: Solids are usually more soluble in hot
than in cold water.
In the process of solution we have three cases:
1. Endothermic reaction: Increase in the temperature
lead to increase solubility (positive heat of solution).
2. Exothermic reaction: Increase in the temperature
result in decrease solubility (negative heat of solution).
3. When heat is neither absorbed nor given off in the
process of solution: Increase or decrease in the
temperature results in no effect on the solubility.
Solubility against rate of solution: 

A distinction should be made between degree of solubility (Amount

of a solute dissolved in a solvent at a certain temperature) and rate of
dissolution.
Rate of dissolution is the speed at which the solute goes into solution
Rate of dissolution = ΔC/Δt = mg/ml/min.
Rate of dissolution depends on:
Particle size of solute: Reduction in particle size results in increase
S.A. and increase rate of dissolution.
Agitation: Increase agitation result in increase rate of dissolution by
removing the more concentrated solution from the surface of solute
and bringing in less concentrated solvent.
Heating: Results in increase solubility by increase the frequency with
which solvent molecule collides with the surface of dissolving material.
Relative terms of solubility
Descriptive terms Parts of solvents required for one
part of solute
Very soluble <1
Freely soluble 1-10
soluble 10-30
Sparingly soluble 30-100
Slightly soluble 100-1000
Very slightly soluble 1000-10,000
Practically insoluble or insoluble > 10,000
Factors affecting solubility
Effect of molecular structure :
The more nearly solute and solvent are alike molecular
structure the greater the solubility of one in the other
(like dissolve the like).
Water is composed of covalent molecules which are
described as polar structures with strong dipole
characteristics (negative and positive regions).
 Polar solvents like water will dissolve salts and other

electrolyte readily so they are poor solvents for non

polar substances.
Polar liquids may act as solvent when it and the solute
are capable of complexation by H-bond formation e.g.
water and alcohol of low M.wt. As the M.wt of the
alcohol increase resulting in a decrease in polarity and
decrease in the solubility in water.
How to predict solubility
The more nearly solvents and solutes are alike structurally,
the more rapidly solution takes place.
Polar liquids dissolve electrovalent compounds readily, but
they are poor solvents for non polar substances. On other
hand , non polar liquids are required for non polar solutes.
Polar liquids are miscible with other polar liquids, but
slightly miscible with non-polar liquids.
Complex organic compounds which have polar and non
polar groups in their molecules may dissolve in polar liquids.
Semipolar liquids ,such as ethyl alcohol pocesses some of the
properties of both polar and nonpolar solvents.
Effect of pH on solubility
 Organic substances are either weak acids or weak bases.
Their aqueous solubility depends on pH of solvent.
 The solubility in water of weak organic acids such as
barbiturates & sulfonamides is increased as the pH
increased by addition of base .This increase in solubility is
due to the formation of water soluble salts.
 therefore:
 If the pH of Phenobarbital solution is increased above 5.5
by addition of strong base the solubility will increase.
 If the pH of Phenobarbital solution is decrease by addition
of strong acid Phenobarbital (free acid) will precipitate.
 The solubility in water of weak organic base
(alkaloids) increase as the pH decrease by
addition of acid due to the formation of water
soluble salts
 If the pH of aqueous solution of salt is

increased by addition of base atropine (free

base will be precipitate).
 At a given pH the degree of ionization of a weakly acid or basic drug
depends on its pka value which is the –ve Log of its dissociation constant.
For weak acidic drugs:
S - So
pH = pKa +Log ---------------
So
S = molar concentration of drug (dissociated and undissociated) species
in solution.
So=molar solubility of undissociated species.
 This equation derived from Handerson –Hasselbach equation.
For weak basic drug:
So
pH= pKw – pKb + log --------------
S - So
 Note: These equations may be used to calculate the pH at which a weak
acids or bases will precipitate from solution of its salt.
Pharmaceutical methods to increase solubility

1) Adjust PH: for weak acidic or basic drugs, their solubility will be
affected by the PH of the solution and the degree of ionization
depends on the pKa of the compound.
2) Co-solvents : changing the polarity of the solvent system.
3) surfactants (SAA): micelle formation.
4) Complexation: formation of soluble complex by the addition of a
complexing agent ex: NaI, Na EDTA, cyclodextrine, Lugolʼs solution:
iodine is slightly soluble in water (1gm in 3000ml of water) but
freely soluble in solution of sodium iodide forming tri-iodide ion
complex.
5) Salt formation: weak acidic or basic drugs having low aqueous
solubility therefore, a more soluble salt is prepared by reaction with
strong base or strong acid, (atropine sulfate, diclofenac sodium)
Effect of added substances on
solubility
 Salting-in: addition of an electrolyte to a
non-electrolyte solution cause an increase in
solubility.
 Salting-out: addition of a soluble salt to a

solution of slightly soluble salt having a

common ion will cause precipitation of the
slightly soluble salt (decrease solubility).
Water soluble inorganic salts
 Common salts of alkali metals (e.g., Na, K, Li, Cs, and Rb)
are usually water soluble (exception: Li2C03).
 Ammonium and quaternary ammonium salts are water
soluble.
 Nitrates, nitrites, acetates, chlorates, and lactates are
generally water soluble (exceptions: silver and mercurous
acetate).
 Sulfates, sulfites, and thiosulfates are generally water
soluble (exceptions: calcium and barium salts).
 Chlorides, bromides, and iodides are water soluble
(exceptions: salts of silver and mercurous ions).
 Acid salts corresponding to an insoluble salt will be more
water soluble than the original salt.
Water insoluble inorganic salts
 Hydroxides and oxides of compounds other than
alkali metal cations and the ammonium ion are
generally water insoluble.
 Sulfides are water insoluble except for their alkali

metal salts.
 Phosphates, carbonates, silicates, borates, and

hypochlorites are water insoluble except for their

alkali metal salts and ammonium salts.
Inorganic salts solubility
 1. If both the cation and anion of an ionic compound are
monovalent, the solute-solute attractive forces are usually
easily overcome, and therefore, these compounds are
generally water soluble (e.g., NaCl, LiBr, Kl, NH4N03, and
NaN02).
 2. If only one of the two ions in an ionic compound is

monovalent, the solute-solute interactions are also usually

easily overcome and the compounds are water soluble (e.g.,
BaCl2, Mgl2, Na2S04, and Na3P04).
 3. If both the cation and anion are multivalent, the solute-

solute interaction may be too great to be overcome by the

solute-solvent interaction, and the compound may have poor
water solubility (e.g., CaS04, BaS04, and BiP04; exceptions:
ZnS04, FeS04) .
Organic molecules
 1. Molecules having one polar functional group are
usually soluble to total chain lengths of five carbons.
 2. Molecules having branched chains are more soluble

than the corresponding straight-chain compound.

 3. Water solubility decreases with an increase in

molecular weight.
 4. Increased structural similarity between solute and

solvent is accompanied by increased solubility.

 5. Polar function groups include OH, CHO, COH,

CHOH, CH2OH, COOH, NO2, CO, NH2 and SO3H .

Thank you