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 Brief introduction and definition
 Advantages
 Types
 Classification on different basis
 Criterias for suspensions
 Evaluation of suspension
 Formulation of suspension
 Preparation techniques
 Comparison of flocculated and deflocculated
 A system in which one substance (The
Dispersed Phase) is distributed, in discrete
units, throughout a second substance (the
continuous Phase).
 Coarse dispersions are of 2 types:
1-Suspensions
2-Emulsions
 Suspensions are heterogeneous biphasic
thermodynamically unstable coarse
dispersion system in which internal phase
is dispersed uniformly throughout the
external phase with the aid of single or
combination of suspending agents.
 particle size of internal phase ranges
between 10 – 15 micrometer.
 For example, Paracetamol suspension,
insulin zinc suspension.
 To increase solubility of insoluble drug
 To mask bitter taste of drug e.g
chloramphenicol palmitate
 To increase drug chemical stability e.g.
Procaine penicillin G
 To achieve controlled/sustained drug
release.
 They exhibit higher rate of bioavailability
than capsule and tablets.
1- Antacid oral suspension
• e.g chloramphenicol palmitate suspension
2- Antibacterial oral suspension
• e.g ciprofloxacin suspension
3- Dry powder for oral suspension
• e.g. zithromax powder for oral suspension
4- Analgesic oral suspension
• e.g. ibuprofen suspension
5- Anthelmentic suspension
 e.g mintezol oral suspension
6- Anticonvulsant oral suspension
• e.g. phenytoin suspension
7- Antifungal oral suspension
• e.g nystatin suspension
8- Antidiarrheal oral suspensions
• e.g bismuth subsalicylates suspension
9- Parenteral suspensions
• e.g Procaine penicillin G Insulin Zinc
Suspension
10- Opthalmic suspensions
• e.g. betoptic S (betaxolol hydrochloride
ophthalmic suspension)
11- Suspension for external use
• e.g.Calamine lotion.
12- Vaccines
• e.g. Cholera vaccine
13- X-ray contrast agent
• e.g. Barium sulphate for examination of
alimentary tract
Suspensions can be classified on the basis of:
 Mode of dispensing
 Concentration
 Particle size
 Sediments
There are 2 types of suspensions:
 Extemporaneous suspensions
 Reconstituted suspensions
 Such suspensions are prepared just before
dispensing to the patients;
• who are unable to swallow solid dosage
forms ( tablet and capsules) e.g. infants
• When no other liquid dosage form is
available.
 USP designs these suspensions as
“ORAL SUSPENSIONS”
 They have high specificity regarding addition
of suspending agent, storage and labeling.
 For example: Pediatric antibiotic
suspensions , rifadin suspensions
 These are powders or granules which are
intended to be suspended in water or some
other vehicle prior to oral administration
 In USP these are designated as:
“FOR ORAL SUSPENSION”
 For example:
• tetracycline suspension and barium sulphate
for oral suspension.
There are 2 types of suspensions:
• Dilute suspensions
• Concentrated suspensions
“ Such suspensions in which
concentration of solid particles ranges from 2
to 10% w/v solid”
 For example: cortisone acetate suspension,
prednisolone acetate suspension.
“Such suspensions in which
concentration of solid particles is 50%w/v”
 For example:
• zinc oxide suspension
There are 3 types of suspensions:
 Colloidal suspensions
 Coarse suspensions
 Nano suspensions
COLLOIDAL
SUSPENSIONS
• Suspensions having particle size of
dispersed solid less than about 1 micron
COARSE
SUSPENSIONS
• Suspensions having particle size of
dispersed phase greater than 1 micron
NANO
SUSPENSIONS
• These suspensions are biphasic colloidal
dispersions of nano sized drug particles
stabilized by surfactants. Size of dispersed
phase is less than 1 micrometre.
On the basis of sedimentation, there are 2
types of suspensions:
• Flocculated suspensions
• Deflocculated suspensions
 In these suspensions, there is a formation of
light, fluffy group of particles held together
by weak vander waals forces.
 In these suspensions, solids are present as
individual particles, they exhibit aggregation
but comparatively low than flocculated
suspensions.
A well-formulated suspension should have:
 Easy and readily redispersion of sedimented
particles , important for uniformity of dose
 No cake formation on setting
 Viscosity optimum for pouring
 Physical, chemical and microbiological
stability
 Pleasing odor, colour and palatability
 Free from gritting particles( in case of
suspensions for external use)
 Proper sterility in case of ophthalmic and
parentral suspensions
Suspensions are evaluated by determining their
physical stability, methods inlude:
 Sedimentation method
 Rheological method
 Electro kinetic method
 Micromeritic method
Sedimentation of particles in a suspension is
governed by several factors:
• particle size
• density of the particles
• density of the vehicle
• viscosity of the vehicle
 The velocity of sedimentation of particles in
a suspension can be determined by using the
Stoke's law.
Where:
 v = velocity of sedimentation
 d = diameter of the particle
 g = acceleration of gravity
 p1 = density of the particle
 p2 = density of the vehicle
 η = viscosity of disperse medium in poise
v =
d2 (p1-p2) g
18 
v =
d2 (p1-p2) g
18 
Two parameters are studied for
determination of sedimentation
 Sedimentation volume
 Degree of flocculation
 Sedimentation volume is a ratio of the
ultimate volume of sediment (Vu) to the
original volume of sediment (VO) before
settling
F = V u / VO
Where:
• Vu = final or ultimate volume of sediment
• VO = original volume of suspension before
settling
 F has values ranging from less than one to
greater than one
• When F < 1 Vu < Vo
• When F =1 Vu = Vo
• When F > 1 Vu > Vo
 Sediment volume is greater than the original
volume due to the network of flocs formed in
the suspension and so loose and fluffy
sediment
 It is the ratio of the sedimentation volume of
the flocculated suspension ,F , to the
sedimentation volume of the deflocculated
suspension, F∞
ß = F / F∞
• F =(Vu/Vo) deflocculated
• F∞ = Vu/Vo) deflocculated
 The minimum value of ß is 1,when
flocculated suspension sedimentation volume
is equal to the sedimentation volume of
deflocculated suspension.
Solid particles can get charged by:
• Selective adsoption of ions at surface
• Ionization of functional group of dispersed
phase
 Two type of electrical potential cotribute to
electrokinetic properties of suspensions:
 Nernst potential
 Zeta Potential
 The flocculated suspension is one in which
zeta potential of particle is -20 to +20 mV.
• The difference in electric
potential between the
actual surface of the
particle and the
electroneutral region is
referred to as Nernst
potential.
Nernst
potential
• The zeta potential is
defined as the difference
in potential between the
surface of the tightly
bound layer (shear plane)
and electro-neutral
region of the solution.
Zeta
Potential
































 
-
-
-
-
-
-
-
-
-
-
-
-
-
- -
--
-
-
-
-
-
-
- - -
- -

-
-

a-
a
b-
b
c-
c
d-
d
Tightly
bound
layer
Diffusion
layer
Electro-neutral
region
Surface
Counterion Shear plan
































 
--
--
--
--
--
--
--
--
--
--
--
--
--
-- --
----
--
--
--
--
--
--
-- -- --
-- --

--
--

a-
a
b-
b
c-
c
d-
d
Tightly
bound
layer
Diffusion
layer
Electro-neutral
region
Surface
Counterion Shear plan
phenomenon of flocculation.
………
Attractive forces exceed the repulsive forces
If the zeta potential is reduced below a certain value
phenomenon of deflocculation.
………
Repulsive forces supersede the attractive
forces
If the zeta potential is higher than the critical value
 The viscosity of the suspension is studied at
different time intervals by using a good
quality of viscometer, it gives useful
information about the stability of suspensions
 Stability of suspension depends upon the
particle size of the dispersed phase
 Any change in particle size with reference to
time will provide useful information
regarding the stability of a suspension
 Three approaches are commonly involved:
 Use of structured vehicle
 Use of controlled flocculation
 Combination of both of the methods
 Thickening or suspending agents.
 They are aqueous solutions of natural and
synthetic gums.
 These are used to increase the viscosity of
the suspension.
 It is applicable only to deflocculated
suspensions
 Entrapped the particle and reduces the
sedimentation of particles.
 E.g. methyl cellulose,sodium carboxy methyl
cellulose, acacia, gelatin and tragacanth
 Controlled flocculation of particles is
obtained by adding flocculating agents,
which are:
 electrolytes ( bismuth subnitrate, monobasic
pot. Phosphate)
 surfactants (ionic and nonionic)
 polymers
 Sometimes suspending agents can be added
to flocculated suspension to retard
sedimentation
 Examples of these agents are:
 Carboxymethylcellulose (CMC),
 Carbopol 934,
 Veegum, and bentonite
 Work by increasing viscosity of liquid
vehicle, and slowing down settling in
accordance to Stokes Law, these agents
mainly prevents caking at the base of any
suspentions. Suspending agent form film
around particle and decrease interparticle
attraction.
 Most suspending agents perform two
functions
• besides acting as a suspending agent
• they also imparts viscosity to the solution
SUSPENSIONS
Suspending agents Stability pH
range
Concentrations used as
suspending
agent
Sodium alginate 4-10 1– 5 %
Methylcellulose 3-11 1– 2 %
Hydroxyethyl cellulose 2-12 1-2%
Hydroxypropyl cellulose 6-8 1-2%
Hydroxypropyl
methylcellulose
3-11 1-2%
CMC 7-9 1-2%
Colloidal
silicon dioxide
0-7.5 2- 4 %
Stability pH range and concentrations of most commonly used suspending agents.
52
Commonly used suspending agents include
• Alginates
• Methylcellulose
• Hydroxyethylcellulose
• Carboxymethylcellulose
• Sodium Carboxymethylcellulose
• Microcrystalline cellulose
• Acacia
• Tragacanth
• Xantham gum
• Bentonite
• Carbomer
• Carrageen
• Powdered cellulose
• Gelatin
 Two main formation methods are used:
 Precipitation methods:
 Dispersion method:
 Three main methods
 Organic solvent precipitation
 Precipitation effected by changing pH of the
medium
 Double decomposition
Water insoluble drugs
Dissolve in organic solvents
Add organic phase to water
 organic solvents include ethanol, methanol,
propylene glycol and polyethylene glycol.
 Applicable to those drugs in which solubility
is dependent on pH value.
Concentrated solution in favorable pH
pour to other system to change pH
On agitation precipitate will form
 E.g estradiol suspension.
 Two water soluble reagent forms a water
insoluble product.
 Eg white lotion NF
Zinc sulphate solution
Solution of sulphurated potash
Precipitate of zinc polysulphide
Vehicle is formulated
solid phase is wetted and dispersed
use of surfactant to ensure wetting of
hydrophobic solids
 Small scale preparation of suspensions
 Large scale preparation of suspensions
Grinding the insoluble materials with a vehicle
containing the wetting agent.
soluble ingredients are dissolved in same
portion of the vehicle
Added to the smooth paste to step1 to get
slurry.
Make up the dispersion to the final volume
 If suspension is made by dispersion process it
is best to achieve pulverization of solid by
micronization technique or spray drying
 If suspension is made by controlled
crystallization, a supersaturated solution
should be formed and then quickly cooled
with rapid stirring.
Floculated suspension Defloculated suspension
 Particles forms loose
aggregates and form
flock
 Rate of sedimentation is
high
 Particles exist as
separate entities form a
cake
Rate of sedimentation is
slow
Floculated defloculated
 Sediment is rapidly
formed
 Sediment is loosely
packed and doesn’t
form a hard cake
 Sediment is easy to re
disperse
 Suspension is not
pleasing in appearance
 The floccules stick to
the sides of the bottle
 Supernatant formed is
clear
 Sediment is slowly
formed
 Sediment is very closely
packed and a hard cake
is formed
 Sediment is difficult to
re disperse
 Suspension is pleasing in
appearance
 They don’t stick to the
sides of the bottle
 Cloudy supernatant
Floculated defloculated
 Sediment is rapidly
formed
 Sediment is loosely
packed and doesn’t
form a hard cake
 Sediment is easy to re
disperse
 Suspension is not
pleasing in appearance
 The floccules stick to
the sides of the bottle
 Supernatant formed is
clear
 Sediment is slowly
formed
 Sediment is very closely
packed and a hard cake
is formed
 Sediment is difficult to
re disperse
 Suspension is pleasing in
appearance
 They don’t stick to the
sides of the bottle
 Cloudy supernatant

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Pharmaceutical suspensions... a brief review

  • 1.
  • 2.
  • 3.  Brief introduction and definition  Advantages  Types  Classification on different basis  Criterias for suspensions  Evaluation of suspension  Formulation of suspension  Preparation techniques  Comparison of flocculated and deflocculated
  • 4.  A system in which one substance (The Dispersed Phase) is distributed, in discrete units, throughout a second substance (the continuous Phase).  Coarse dispersions are of 2 types: 1-Suspensions 2-Emulsions
  • 5.  Suspensions are heterogeneous biphasic thermodynamically unstable coarse dispersion system in which internal phase is dispersed uniformly throughout the external phase with the aid of single or combination of suspending agents.  particle size of internal phase ranges between 10 – 15 micrometer.  For example, Paracetamol suspension, insulin zinc suspension.
  • 6.  To increase solubility of insoluble drug  To mask bitter taste of drug e.g chloramphenicol palmitate  To increase drug chemical stability e.g. Procaine penicillin G  To achieve controlled/sustained drug release.  They exhibit higher rate of bioavailability than capsule and tablets.
  • 7. 1- Antacid oral suspension • e.g chloramphenicol palmitate suspension
  • 8. 2- Antibacterial oral suspension • e.g ciprofloxacin suspension
  • 9. 3- Dry powder for oral suspension • e.g. zithromax powder for oral suspension
  • 10. 4- Analgesic oral suspension • e.g. ibuprofen suspension
  • 11. 5- Anthelmentic suspension  e.g mintezol oral suspension 6- Anticonvulsant oral suspension • e.g. phenytoin suspension
  • 12. 7- Antifungal oral suspension • e.g nystatin suspension
  • 13. 8- Antidiarrheal oral suspensions • e.g bismuth subsalicylates suspension
  • 14. 9- Parenteral suspensions • e.g Procaine penicillin G Insulin Zinc Suspension 10- Opthalmic suspensions • e.g. betoptic S (betaxolol hydrochloride ophthalmic suspension)
  • 15. 11- Suspension for external use • e.g.Calamine lotion.
  • 16. 12- Vaccines • e.g. Cholera vaccine 13- X-ray contrast agent • e.g. Barium sulphate for examination of alimentary tract
  • 17. Suspensions can be classified on the basis of:  Mode of dispensing  Concentration  Particle size  Sediments
  • 18. There are 2 types of suspensions:  Extemporaneous suspensions  Reconstituted suspensions
  • 19.  Such suspensions are prepared just before dispensing to the patients; • who are unable to swallow solid dosage forms ( tablet and capsules) e.g. infants • When no other liquid dosage form is available.  USP designs these suspensions as “ORAL SUSPENSIONS”
  • 20.  They have high specificity regarding addition of suspending agent, storage and labeling.  For example: Pediatric antibiotic suspensions , rifadin suspensions
  • 21.  These are powders or granules which are intended to be suspended in water or some other vehicle prior to oral administration  In USP these are designated as: “FOR ORAL SUSPENSION”  For example: • tetracycline suspension and barium sulphate for oral suspension.
  • 22. There are 2 types of suspensions: • Dilute suspensions • Concentrated suspensions
  • 23. “ Such suspensions in which concentration of solid particles ranges from 2 to 10% w/v solid”  For example: cortisone acetate suspension, prednisolone acetate suspension.
  • 24. “Such suspensions in which concentration of solid particles is 50%w/v”  For example: • zinc oxide suspension
  • 25. There are 3 types of suspensions:  Colloidal suspensions  Coarse suspensions  Nano suspensions
  • 26. COLLOIDAL SUSPENSIONS • Suspensions having particle size of dispersed solid less than about 1 micron COARSE SUSPENSIONS • Suspensions having particle size of dispersed phase greater than 1 micron NANO SUSPENSIONS • These suspensions are biphasic colloidal dispersions of nano sized drug particles stabilized by surfactants. Size of dispersed phase is less than 1 micrometre.
  • 27. On the basis of sedimentation, there are 2 types of suspensions: • Flocculated suspensions • Deflocculated suspensions
  • 28.  In these suspensions, there is a formation of light, fluffy group of particles held together by weak vander waals forces.
  • 29.  In these suspensions, solids are present as individual particles, they exhibit aggregation but comparatively low than flocculated suspensions.
  • 30. A well-formulated suspension should have:  Easy and readily redispersion of sedimented particles , important for uniformity of dose  No cake formation on setting  Viscosity optimum for pouring  Physical, chemical and microbiological stability  Pleasing odor, colour and palatability  Free from gritting particles( in case of suspensions for external use)
  • 31.  Proper sterility in case of ophthalmic and parentral suspensions
  • 32. Suspensions are evaluated by determining their physical stability, methods inlude:  Sedimentation method  Rheological method  Electro kinetic method  Micromeritic method
  • 33. Sedimentation of particles in a suspension is governed by several factors: • particle size • density of the particles • density of the vehicle • viscosity of the vehicle  The velocity of sedimentation of particles in a suspension can be determined by using the Stoke's law.
  • 34. Where:  v = velocity of sedimentation  d = diameter of the particle  g = acceleration of gravity  p1 = density of the particle  p2 = density of the vehicle  η = viscosity of disperse medium in poise v = d2 (p1-p2) g 18  v = d2 (p1-p2) g 18 
  • 35. Two parameters are studied for determination of sedimentation  Sedimentation volume  Degree of flocculation
  • 36.  Sedimentation volume is a ratio of the ultimate volume of sediment (Vu) to the original volume of sediment (VO) before settling F = V u / VO Where: • Vu = final or ultimate volume of sediment • VO = original volume of suspension before settling
  • 37.  F has values ranging from less than one to greater than one • When F < 1 Vu < Vo • When F =1 Vu = Vo • When F > 1 Vu > Vo  Sediment volume is greater than the original volume due to the network of flocs formed in the suspension and so loose and fluffy sediment
  • 38.  It is the ratio of the sedimentation volume of the flocculated suspension ,F , to the sedimentation volume of the deflocculated suspension, F∞ ß = F / F∞ • F =(Vu/Vo) deflocculated • F∞ = Vu/Vo) deflocculated  The minimum value of ß is 1,when flocculated suspension sedimentation volume is equal to the sedimentation volume of deflocculated suspension.
  • 39. Solid particles can get charged by: • Selective adsoption of ions at surface • Ionization of functional group of dispersed phase  Two type of electrical potential cotribute to electrokinetic properties of suspensions:  Nernst potential  Zeta Potential  The flocculated suspension is one in which zeta potential of particle is -20 to +20 mV.
  • 40. • The difference in electric potential between the actual surface of the particle and the electroneutral region is referred to as Nernst potential. Nernst potential • The zeta potential is defined as the difference in potential between the surface of the tightly bound layer (shear plane) and electro-neutral region of the solution. Zeta Potential
  • 41.                                   - - - - - - - - - - - - - - - -- - - - - - - - - - - -  - -  a- a b- b c- c d- d Tightly bound layer Diffusion layer Electro-neutral region Surface Counterion Shear plan                                   -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- ---- -- -- -- -- -- -- -- -- -- -- --  -- --  a- a b- b c- c d- d Tightly bound layer Diffusion layer Electro-neutral region Surface Counterion Shear plan
  • 42. phenomenon of flocculation. ……… Attractive forces exceed the repulsive forces If the zeta potential is reduced below a certain value
  • 43. phenomenon of deflocculation. ……… Repulsive forces supersede the attractive forces If the zeta potential is higher than the critical value
  • 44.  The viscosity of the suspension is studied at different time intervals by using a good quality of viscometer, it gives useful information about the stability of suspensions
  • 45.  Stability of suspension depends upon the particle size of the dispersed phase  Any change in particle size with reference to time will provide useful information regarding the stability of a suspension
  • 46.  Three approaches are commonly involved:  Use of structured vehicle  Use of controlled flocculation  Combination of both of the methods
  • 47.  Thickening or suspending agents.  They are aqueous solutions of natural and synthetic gums.  These are used to increase the viscosity of the suspension.  It is applicable only to deflocculated suspensions  Entrapped the particle and reduces the sedimentation of particles.  E.g. methyl cellulose,sodium carboxy methyl cellulose, acacia, gelatin and tragacanth
  • 48.  Controlled flocculation of particles is obtained by adding flocculating agents, which are:  electrolytes ( bismuth subnitrate, monobasic pot. Phosphate)  surfactants (ionic and nonionic)  polymers
  • 49.  Sometimes suspending agents can be added to flocculated suspension to retard sedimentation  Examples of these agents are:  Carboxymethylcellulose (CMC),  Carbopol 934,  Veegum, and bentonite
  • 50.
  • 51.  Work by increasing viscosity of liquid vehicle, and slowing down settling in accordance to Stokes Law, these agents mainly prevents caking at the base of any suspentions. Suspending agent form film around particle and decrease interparticle attraction.  Most suspending agents perform two functions • besides acting as a suspending agent • they also imparts viscosity to the solution
  • 52. SUSPENSIONS Suspending agents Stability pH range Concentrations used as suspending agent Sodium alginate 4-10 1– 5 % Methylcellulose 3-11 1– 2 % Hydroxyethyl cellulose 2-12 1-2% Hydroxypropyl cellulose 6-8 1-2% Hydroxypropyl methylcellulose 3-11 1-2% CMC 7-9 1-2% Colloidal silicon dioxide 0-7.5 2- 4 % Stability pH range and concentrations of most commonly used suspending agents. 52
  • 53. Commonly used suspending agents include • Alginates • Methylcellulose • Hydroxyethylcellulose • Carboxymethylcellulose • Sodium Carboxymethylcellulose • Microcrystalline cellulose • Acacia • Tragacanth • Xantham gum • Bentonite • Carbomer • Carrageen • Powdered cellulose • Gelatin
  • 54.  Two main formation methods are used:  Precipitation methods:  Dispersion method:
  • 55.  Three main methods  Organic solvent precipitation  Precipitation effected by changing pH of the medium  Double decomposition
  • 56. Water insoluble drugs Dissolve in organic solvents Add organic phase to water  organic solvents include ethanol, methanol, propylene glycol and polyethylene glycol.
  • 57.  Applicable to those drugs in which solubility is dependent on pH value. Concentrated solution in favorable pH pour to other system to change pH On agitation precipitate will form  E.g estradiol suspension.
  • 58.  Two water soluble reagent forms a water insoluble product.  Eg white lotion NF Zinc sulphate solution Solution of sulphurated potash Precipitate of zinc polysulphide
  • 59. Vehicle is formulated solid phase is wetted and dispersed use of surfactant to ensure wetting of hydrophobic solids
  • 60.  Small scale preparation of suspensions  Large scale preparation of suspensions
  • 61. Grinding the insoluble materials with a vehicle containing the wetting agent. soluble ingredients are dissolved in same portion of the vehicle Added to the smooth paste to step1 to get slurry. Make up the dispersion to the final volume
  • 62.
  • 63.  If suspension is made by dispersion process it is best to achieve pulverization of solid by micronization technique or spray drying  If suspension is made by controlled crystallization, a supersaturated solution should be formed and then quickly cooled with rapid stirring.
  • 64.
  • 65. Floculated suspension Defloculated suspension  Particles forms loose aggregates and form flock  Rate of sedimentation is high  Particles exist as separate entities form a cake Rate of sedimentation is slow
  • 66. Floculated defloculated  Sediment is rapidly formed  Sediment is loosely packed and doesn’t form a hard cake  Sediment is easy to re disperse  Suspension is not pleasing in appearance  The floccules stick to the sides of the bottle  Supernatant formed is clear  Sediment is slowly formed  Sediment is very closely packed and a hard cake is formed  Sediment is difficult to re disperse  Suspension is pleasing in appearance  They don’t stick to the sides of the bottle  Cloudy supernatant
  • 67. Floculated defloculated  Sediment is rapidly formed  Sediment is loosely packed and doesn’t form a hard cake  Sediment is easy to re disperse  Suspension is not pleasing in appearance  The floccules stick to the sides of the bottle  Supernatant formed is clear  Sediment is slowly formed  Sediment is very closely packed and a hard cake is formed  Sediment is difficult to re disperse  Suspension is pleasing in appearance  They don’t stick to the sides of the bottle  Cloudy supernatant