GROUPMEMBERS:AHLA,AMNA,TAYYABA,UMAIMA,SABA

,MAHNOOR,HANEEN,NEHA,RAMSHA,SYEDA AREEBA FATIMA.

GROUP: 6
SUBJECT: PHYSICAL PHARMACY.
ASSIGNMENT TOPIC: SOLUBILITY.
DEPARTEMENT: PHARMACY (1 PROF).
SHIFT: MORNING.
INCHARGE: MISS JAVERIA SHEIKH.
 ASSIGNMENT
SOLUBILITY

ABSTRACT:
 (BY UMAIMA NADEEM)

INTRODUCTION:
Solubility:
Solubility the ability of a solid, liquid, or gaseous chemical substance to dissolve in solvent and form a
solution. Solubility is defined in quantitative term as the concentration of solute in a saturated solution at
a certain temperature, and in a qualitative way, it can be defined as the spontaneous interaction of two or
more substance to form a homogenous molecular dispersion. According to an IUPAC definition,
solubility is the analytical composition of a saturated solution expressed as a proportional of a designated
solute in a designated solvent. An unsaturated or subsaturated solution is one containing the dissolved
solute in a concentration below that necessary for complete saturation at a definite temperature .A
supersaturated solution is one that contain more of the dissolved solute that it would normally contain at a
definite temperature were the undissolved solute present. Solubility is an intrinsic property that can be
altered only by chemical modification of the molecules, in contrast to this, dissolution is an extrinsic
property that can be influenced by various chemical, physical, or crystallographic mean such as
complexation, particle size, surface properties, solid-state modification, or solubilization enhancing
formulation strategies. Generally speaking, the solubility of a compound depends on the physical and
chemical properties of the solute and the solvent as well as on such factors as temperature, pressure, the
pH of the solution. Solubility is important on pharmaceutical level such as, it is one of the important
parameter to achieve desired concentration of drug in systemic circulation for achieving required
pharmacological response, and solubility behavior of drugs one of the important of preformulation test for
poorly soluble drug, by this, active ingredient is stable in dosage form, desired quantity achieved etc.

Solubilization:
Solubilization is increasing the solubility of poorly soluble substance with surface active agent.

Solvent–SoluteInteractions:
The pharmacist knows that water is a good solvent for salts, sugars, and similar compounds, whereas
mineral oil is often a solvent for substances that are normally only slightly soluble in water. These
empirical findings are summarized in the statement, ―like dissolves like.

Polar Solvents:
It contains strong dipolar molecules and exhibit hydrogen bonding properties. Polar solvents generally
dissolve polar solutes.

Semi polar solvents:

These solvents are also made of strong dipolar molecules, however, they do not form hydrogen bonds.
They serve as a medium for a multi component homogeneous system containing polar and non-polar
solvents.

Non polar solvents:

It contains molecules that have only a small or dipolar character. This solvent dissolve non polar solvent.
(BY TAYYABA ARIF)

FACTORS AFFECTING THE SOLUBILITY

There are many factors which affects the solubility some factors are discuss below:

 Temperature
 Pressure
 Nature of surfactant
 Nature of solvent
 Polarity
 Stirring
 Surface Area
 Molecular size

TEMPERATURE:
Solubility is directly proportional to temperature. If we increase temperature solubility increases. The
situationis though different for gases. With increase of the temperature they became less soluble in
eachother and in water, but more soluble in organic solvent.
Solubility α Temperature

EXAMPLE:
If we add 5 grams of sugar in 100 grams of water at room temperature sugar will dissolve than we
increase temperature and add 20 grams of sugar in 100 grams of water than sugar also dissolve this means
that when we increase temperature the solubility of sugar increases.

PRESSURE:
Pressure also affect the solubility indirectly because pressure is directly proportional to temperature if we
increase temperature pressure also increases than solubility also increases.
Pressure α Temperature α Pressure

EXAMPLE:
When opening a bottle of carbonate drink. When we decrease the pressure in a bottle , the gas that was
dissolved in the drink bubbles out of it.

NATURE OF SURFACTANTS:
Solubility also affected by nature of surfactants.The longer The longer the hydrophobic chain of a
surfactant , the larger would b the micelles size , resulting in greatorsolubilization. Although increased in
chain length of hydrophilic results in overall increase in solubility.
EXAMPLE:
Solubility of dexamethasone increase in n-alkyl polyoxyethylene with an increase in oxymethylene
number while keeping the alkyl length constant at 16 carbon long.

NATURE OF SOLVENT:
Nature of solvent also affect the solubility. The solvents may be polar or non polar in which solute can
dissolve easily. Nature of solvent is very important i.e water is universal solvent. Some solvents are
soluble, partially soluble and insoluble.

POLARITY:
Solubility also affected by polarity. In most cases solutes dissolve in solvents that have a similar polarity.
Chemist use a popular aphorism to describe this feature of solutes and solvent. “ LIKE DISSOLVES
LIKE “. Non polar solutes donotdissolve in polar solvents. Polar solutes dissolve in polar solvent and non
polar solute dissolve in non polar solvent.

EXAMPLE:
Glycoproteins dissolve in ether rather than water because glycoprotein is non polar and it dissolve in non
polar solvent i.e: ether. It does not dissolve in polar solvent

STIRRING:
Solubility also affected by stirring indirectly. Stirring increase the movement of solvent molecules or
increase the kinetic energy of the molecule. Stirring only speed up the process.

EXAMPLE:
If we put sugar in the tea and does not stir, it will not dissolve. Actually, if we left the tea to stand for a
long enough time, the sugar would dissolve slowly.

SURFACE AREA:
Solubility also affected by surface area. If the greator the surface area greator would be solubility.
Because molecules are highly exposure to the solvent molecules.

EXAMPLE:
We take drug in a dosage form they take much more time to solubilize but when we take drug in powder
form they take short time to dissolve and effect produce readily.

MOLECULAR SIZE:
Solubility also affected by molecular size. Greator the molecular size solubility decreases. Smaller
molecules soluble easily as compared to bigger molecules.
(BY RAMSHA AQEEL)

ADDITIVE’S EFFECT

It includes: -
ADDITION OF INDIFFERENT IONS:
The activity of a specific ion is interconnected to its effective concentration. The activity of a specific ion
is interconnected to its effective concentration .In general , this is lower than the actual concentration
because some ions produced by dissociation of the electrolyte are strongly associated with other
oppositely charged ions and do not contribute so effectively to the properties of the system as completely
unallocated ions.

EFFECT OF ELECTROLYTES ON THE SOLUBILITY OF NON-ELECTROLYTES:

Non electrolyte do not dissociate into ions in aqueous solution , and in dilute solution the dissolved
species therefore , consist of single molecules. Their solubility in water depends upon weak inter
molecular bonds between their molecule and those of water. The presence of very soluble electrolyte, the
ions of which have a marked affinity for water, will reduce the solubility of a nonelectrolyte by competing
for the aqueous solvent and breaking the intermolecular bonds between the nonelectrolyte and water.

EFFECT OF NON-ELECTROLYTES ON THE SOLUBILITY OF ELECTROLYTES:

The solubility of electrolytes depends on the dissociation of dissolved molecules into ions. This
dissociation is affected by the dielectric constants of solvent, which is a measure of the polar nature of the
solvent. Liquids with the high dielectric constant (e.g. water) are able to reduce the attractive forces that
operate between oppositely charged ions produced by dissociation of an electrolyte.
If a water soluble non-electrolyte, such as alcohol, is added to an aqueous solution of sparingly soluble
electrolyte,the solubility of the latter is decreased because the alcohol lowers the dielectric constant of the
solvent and ionic dissociation of the electrolyte becomes more difficult.
(BY MAHNOOR HUSSAIN)

COMMON ION EFFECT:

Whenever a solution of ionic substance comes in contact with an excipient which is also ionic in
nature and has a common ion to that of the ionic substance in solution, the solubility of the ionic
substance decreases.
EXAMPLE:
If we try to dissolve NaCl in a solution where Cl- ions are already present then the amount of NaCl
dissolved to reach the saturation point would be lower as compared to the solubility of NaCl in pure
solvent which does not contain common ion.
This phenomenon is called common ion effect. It plays major role in pharmaceutical area.
FORMATION OF COMPLEX:
The solubility of a solute in a particular solvent is also influenced by addition of a third substance
(excipient) which forms a complex with solute. The nature of this solute determines the solubility of a
solute. If the complex formed has high solubility then the solubility of the solute increases but if the
solubility of the complex is low the the solubility of the solute decreases.
( BY AHLA ALAM)

CONCEPT OF MICELLE AND CMC:

 INTRODUCTION:
 In dilute solution Amphiphiles tend to reduce Surface tension As concentration molecules of
amphiphiles goes on increasing they disturb hydrogen structure, to minimize the disturbance
molecules tend to form aggregate into a structure Structure called as micelle and Amphiphilic
molecule Surface Active Agent
 SURFACTANT:

A micelle is an aggregates of Surfactant molecules dispersed in liquid collide Surfactants

(amphiphilic molecules) composed of a hydrophilic moiety known as head and a hydrophobic
moiety known as tail. Cohesive forces between molecules down into liquid the intermolecular
attractive forces is called surface tension.
 MICELLE:
A micelle is an aggregate of monomer surfactant molecules dispersed in a liquid colloid.
Hydrophilic "head" regions in contact with surrounding solvent, sequestering the hydrophobic tail
regions in the micelle centre. (oil-in-water micelle). Inverse micelles have the head groups at the
centre with the tails extending out (water-in-oil micelle).
 MICELLE FORMATION:
The process of forming micelle is known as micellization. Typical micelle is Spherical in
structure which contain 50-100 monomers.Number of monomers to form micelle is called as
aggregation number.
OIL IN WATER TYPE: Because of arrangement monomers micelle is capable to hold lipidic
nature drug at centre.
 WATER IN OIL TYPE: In Reversed micelle at middle able to hold relatively large amounts of
water in their interior. In that way, a "pocket" is formed which is particularly suited for the
dissolution and transportation of polar solutes through a non polar solvent.

 CRITICAL MICELLE CONCENTRATION (CMC):

The lowest concentration at which micelles first appear is called the critical concentration for
micelle formation The critical micelle concentration is the point atwhich surfactant molecules
aggregate together in the liquid to form groups known as micelles.
The critical micelle concentration of a surfactantindicates the point at which surface active properties are
at an optimum and performance is maximised. The CMC is the concentration above surfactant when
micelles will form spontaneously. Increase in concentration of surfactant beyond CMCchange number
size or shape but not provide increase in concentration of monomeric species.
  DETERMINATION OF THE CMC:
Micelles are formed at the critical micelle concentration (CMC), which is detected as an
inflection point in physical properties. • surface tension, • Conductivity, • Turbidity, • Osmotic
Pressure.
 SOLUBILIZATION:
Micelle can be used to increase the solubility of material that are normally insoluble or poorly
soluble in dispersed medium phenomenon called as solubilization Importance Hydrophilic drugs
can be adsorbed on the surface ofthe micelle.

Drugs with intermediate Solubility should be located in intermediate positions within the micelle
such as between the hydrophilic head group of Peo Micelles In the Palisade Layer between the
hydrophilic group and the first few carbon atoms of the hydrophobic group , that is the outer core.
Completely insoluble hydrophobic drugs may belocated in the Inner Core of the micelle.
 CONCLUSION:

By using Phenomenon of micellization we improve solubility of API Considering factor of CMC

we modify micelle size. Shape & release profile Applying this knowledge in field of Pharmacy
Improve API stability Maintain Bioavailability long period Research is continue in Targeted
DDS (Cancer).
( BY AMNA ASAD)

McBain Theory:
In 1913 James William McBain at the University of Bristol postulated the existence of "colloidal ions" to
explain the good electrolytic conductivity of sodium palmitate solutions. These highly mobile,
spontaneously formed clusters called as micelles. micelle is responsible for many of the physical
properties of solutions of surfactants , a number of phenomena remain unexplained if other shapes are not
considered.
According to McBain theory two types of micelle exists :

Spherical:
It is smaller molecule of micelle which is chargesd and available at every concentration i.e before CMC
,at CMC , after CMC

Lamellar:
It is larger neutral molecule available only at CMC and after CMC .They are undissociated
,promote solubilization and responsible for low osmotic pressure and also responsible for
reduction in conductance.They both are accounts for molar concentration of surfactant solutions.
On the basis of arrangement micelles are of two type:

 normal micelle
 reverse micelle

Normal Micelle:
They are in monomeric form .Normal micelles are formed in water and in other highly polar media. Their
polar heads stretch out and the assembled hydrophobic tails form the low-polar 'nano-phase', which can
solubilize low-polar molecules.alsocalled as direct micelle.
Reverse Micelle /Inverse Micelle :
Reverse micelles formed in low polar solvents the low-polar tails stretch out and polar heads assemble.
They can solubilize water and other highly polar molecules.

(BY SYEDA AREEBA FATIMA)

SURFACTANT/SURFACE ACTIVE AGENT

DEFINITION:
Surfactant or surface active agent or amphiphiles are chemical compound that tend to accumulate at the
boundary (that is interface) between two phases. Therefore they are adsorbed at the various interfaces
existing between solid or liquid, resulting in changing the nature of interfaces .This has huge significance
in pharmacy such as in the formation of emulsions or suspension and solubilization of poorly solute
drugs.
The word surfactant is a blend of surface-active-agent

COMPOSITION:
Surfactant are usually organic compound that are amphiphilic, meaning they contain both hydrophobic
group (their tail) and hydrophilic group (their head). Therefore a surfactant contain both water -insoluble
(or oil soluble) component and water-soluble component.
Surfactant will diffuse in water and adsorbed at interfaces between Nair and water or at the
interface between oil and water in the case where water is mixed with oil. The water insoluble
hydrophobic group may extend out of the bulk water phase into the air or into the oil phase, while the
water-soluble head group remains in the water phase.

EXAMPLE:
Sodium stearate the most common component of most soap, which comprises about 50% of commercial
surfactant.

CLASSIFICATION:
On the basis of

 Hydrophobic
 Hydrophilic
On the basis of their charge surfactant may be classified as:

 ionic
 cationic
 amphoteric ( zwitter ionic )
 nonionic
 bio surfactant

ANIONIC SURFACTANT:
This surfactant contains carboxylate, sulfonate or sulfate groups

EXAMPLE:
Include sodium stearate, sodium dodecyl sulfate and sodium lauryl sulfate.

CATIONIC SURFACTANT:
These surfactant contain amine salt or quaternary ammonium salts .

EXAMPLE:
Cetrimonium bromide

AMPHOTERIC SURFACTANT:
This surfactant contain carboxylate or phosphate groups as the anion and amino or quaternary ammonium
group consisting of carboxylate anions and amine cations are called polypeptide or protein and the latter
group consisting of phosphate anion and quaternary ammonium cation re called natural phospholipid such
as lecithin and cephalin.

NONIONIC SURFACTANT:
This surfactant do not have any charge. They are generally insoluble in water and have low hydrophilic –
lipophilic – balance (HLB)
Nonionic surfactants are less sensitive to water hardness than anionic surfactant and they foam less
strongly.

BIO SURFACTANT:
Bios surfactants are surface active substance synthesized by living cell .Bio surfactant enhance the
emulsification of hydrocarbon oil recovery.
Several microorganisms are know to synthesis surfactant most of them are bacteria and yeast.
BODY SURFACTANT:
The human body produces different type of surfactant in different part or organ for different purpose
Pulmonary surfactant is produced in lungs in order to facilitate breathing by increasing total lungs
capacity TLC and lungs compliance.

USE OF SURFACTANT:
Surfactant use as Wetting agent, emulsifying agent , solubilizing agents , foaming agent , antifoaming
agent , flocculating agent ( suspending agent ) , DE flocculants ( BY NEHA IMAM)

IMPORTANCE OF SOLUBILITY
Oral ingestion is the most convenient and commonly employed route of drug delivery due to its ease of
administration, high patient compliance, cost effectiveness, least sterility constraints, and flexibility in the
design of dosage form. As a result, many of the generic drug companies are inclined more to produce
bioequivalent oral drug products
However, the major challenge with the design of oral dosage forms lies with their poor bioavailability.
The oral bioavailability depends on several factors including aqueous solubility, drug permeability,
dissolution rate, first-pass metabolism, presystemic metabolism, and susceptibility to efflux mechanisms.
The most frequent causes of low oral bioavailability are attributed to poor solubility and low permeability.
Solubility also plays a major role for other dosage forms like parenteral formulations as well Solubility is
one of the important parameters to achieve desired concentration of drug in systemic circulation for
achieving required pharmacological response. Poorly water soluble drugs often require high doses in
order to reach therapeutic plasma concentrations after oral administration. Low aqueous solubility is the
major problem encountered with formulation development of new chemical entities as well as generic
development. Any drug to be absorbed must be present in the form of an aqueous solution at the site of
absorption. Water is the solvent of choice for liquid pharmaceutical formulations. Most of the drugs are
either weakly acidic or weakly basic having poor aqueous solubility.
More than 40% NCEs (new chemical entities) developed in pharmaceutical industry are practically
insoluble in water. These poorly water soluble drugs having slow drug absorption leads to inadequate and
variable bioavailability and gastrointestinal mucosal toxicity. For orally administered drugs solubility is
the most important one rate limiting parameter to achieve their desired concentration in systemic
circulation for pharmacological response. Problem of solubility is a major challenge for formulation
scientist.
The improvement of drug solubility thereby its oral bio-availability remains one of the most challenging
aspects of drug development process especially for oral-drug delivery system. There are numerous
approaches available and reported in literature to enhance the solubility of poorly water-soluble drugs.
The techniques are chosen on the basis of certain aspects such as properties of drug under consideration,
nature of recipients to be selected, and nature of intended dosage form.
(BY SABA GUL KHAN)
REFERANCES:
Aulton’s Pharmaceutics
Edited by Michael E. Aulton and Kevin M.G. Taylor
4th edition
Churchill Livingstone Elsevier
(MAHNOOR HUSSAIN)
Reference: Clugston M, Fleming R. Advanced Chemistry. 1st edition. Oxford, UK: Oxford Publishing;
2000.[Google Scholar]
( SABA GUL KHAN )
[cited:2005]
https://chemistry.tutorvista.com/biochemistry/micelle.html
[cited:january 15 ,2001]
https://en.wikipedia.org/wiki/Micelle
Tharwat F. Tadros(2018). classification of surfactant, their solution properties and self assembly structure.
Basic Theory of Interfacial Phenomena and Colloid Stability.volume 1.pg no 83. Published by Walter de
Gruyter GmbH & Co KG.
(syedaAreeba Fatima)
REFERENCE OF WEB :
[2001] https://en.wikipedia.org/wiki/Surfactant[ 7 March 2019]
REFERENCE OF BOOK :
Edited by Alekhak Dash (RPH , PHD ) , Somnath Singh ( PHD) , Justin Tolman ( PHAR D , PHD ) ;
Solubilization ; Pharmaceutics basic principles and application to pharmacy practices ;2014;56;
ELSEVIER
( byneha imam)

Reference:
Patrick J. Sinko, (2006), Solubility And Distribution Phenomena, Martin’s Physical Pharmacy And
Pharmaceutical Science, 6 Edition, Pg. no 182, Published by Wolters Kluwer (India) Pvt Ltd

[Cited: 2012]
http://dx.doi.org/10.5402/2012/195727

[cited:2005]
https://chemistry.tutorvista.com/inorganic-chemistry/solvent.html
( bytayyabaarif)
REFRENCES:-
 Website For Common Ion Effect: [Cited: 10 Oct 2003] , [Revised: 14 March 2019] ,
URL: https://en.m.wikipedia.org/wiki/Common-ion_effect
 Book For Formation of Complex: Edited By: Michael E.Aulton and Kevin M.G. Taylor ,
Chapter Name: Dissolution and Solubility, Book Name: Aulton'sPharmaceutic (The design and
manufacture if medicines), Edition: Fourth Edition, Year: 2013, Pg No: 33
Publisher: Churchill Livingstone Elsevier.
( byahla)
https://www.slideshare.net/AkshayPawar25/concept-of-micelle-cmc?qid=de
(amnaasad)
Edited by Alekhak Dash (RPH , PHD ) , Somnath Singh ( PHD) , Justin Tolman ( PHAR D , PHD ) ;
Solubilization ; Pharmaceutics basic principles and application to pharmacy practices ;2014;59-62;
ELSEVIER
( BY RAMSHA AQEEL)