SUSPENSIONS
WAQAR AHMED
PHARM.D, M.Phil
(PHARMACEUTICS)
DEFINITIONS
 A Pharmaceutical suspension is a disperse system
in which internal phase is dispersed uniformly as
finely divided insoluble particles throughout the
external phase.
 The internal phase consisting of insoluble solid
particles having a specific range of size which is
maintained uniformly throughout the suspending
vehicle with aid of single or combination of
suspending agent.
 The external phase (suspending medium) is
generally aqueous in some instance, may be an
organic or oily liquid for non oral use.
DEFINITIONS
 Suspension may be defined as preparation containing
finely divided drug particles distributed somewhat
uniformly throughout a vehicle in which the drug
exhibits a minimum degree of solubility.
 Suspensions are the biphasic liquid dosage form of
medicaments in which the finely divided solid particles.
 The range of solid particles in suspension from 0.5 to
5.0 micron.
 Suspensions are used in orally, parentally and also
externally.
 They are chemically stable than solution.
DEFINITIONS
 The term "Disperse System" refers to a system in
which one substance (The Dispersed Phase) is
distributed, in discrete units, throughout a second
substance (the continuous Phase or vehicle).
Each phase can exist in solid, liquid, or gaseous
state . . Most suspensions are classified as a
coarse suspension which is a dispersion of
particles with a mean diameter greater than 1µm
(1 to 100 µm. A colloidal suspension is a
dispersion of particles with a mean diameter of
less than 1µm (0.5µm to 1µm).
SEDIMENTATION
 This is a phenomenon which occurs in dispersed
system where the dispersed particles settle to the
bottom of the container. This occurs because the
particles are too large to remain permanently
suspended in the vehicle.
 Therefore suitable suspending agents are added
to retard this process.
SUSPENDING AGENTS
 Suspending agents are substances that are used
to keep finely divided insoluble materials
suspended in a liquid media by preventing there
agglomeration (coming together) and by
imparting viscosity to the dispersion media so
that the particles settle more slowly. Care must
be taken when selecting a suspending agent for
oral preparations as the acid environment of the
stomach may alter the physical characteristics of
the suspension and therefore the rate of release
of the drug from suspension.
 They are various types of suspending agents
Types of Suspending Agents
 1. NATURAL AGENTS
 This class consists of those from. a. Animal source eg
Gelatine b. Plant source eg. Accacia, Tragacanth,
Starch, sea weed (Alginates) c. mineral sources.eg
Bentonite, Kaoline
 2. SEMI-SYNTHETIC AGENTS
 These consist of substituted cellulos (minerals) eg.
Hydroxyethylcellulose , Sodium Carboxymethylcellulose
, methylcellulose, Microcrystalline cellulose
 3. SYNTHETIC AGENTS
 They are synthetic polymers eg carboxypolymethylene
(carbopol), Polyvinyl Alcohol, Polyvinyl Pyrolidone
iodine complex (PVC).
Orally/Syrup form
Parental/Injection form
Ophthalmic/ Used in Eyes
Tropical/External & Cosmetics
Classification of suspensions
 Based On General Classes
I. Oral suspension
II. Externally applied suspension
III. Parenteral suspension
 Based On Proportion Of Solid Particles
I. Dilute suspension (2 to10%w/v solid)
II. Concentrated suspension (50%w/v solid)
Ø Based On Electrokinetic Nature Of Solid Particle
I. Flocculated suspension
II. Deflocculated suspension
 Based On Size Of Solid Particles
I. Colloidal suspension (< 1 micron)
II. Coarse suspension (>1 micron)
III. Nano suspension (10 ng)
Reasons for suspensions
 If patient has a difficulty of swallowing solid
dosage forms (a need for oral liquid dosage
form).
 Faster rate of dissolution and oral absorption
than solid dosage forms, yet slower than
solutions.
 Drugs that have very low solubility are usefully
formulated as suspensions.
 Drugs that have an unpleasant taste in their
soluble forms (e.g., chloramphenicol (soluble)
vs. chloramphenicol palmitate (insoluble )).
Based on General Class
 Oral Suspension e.g. Paracetamol Suspension
 Externally Applied suspension e.g. Calamine
lotion
 Parenteral Suspension e.g. Insulin zinc
suspension
Based on Proportion of Solid
Particles
 Dilute Suspension (2 to 10% w/v solid) e.g.
cortisone acetate, predinsolone acetate
 Concentrated Suspension (50% w/v solid) e.g.
Zinc oxide suspension
 BASED ON ELECTROKINETIC
NATURE OF SOLID PARTICLE
 Flocculated Suspension
 Deflocculated Suspension
Based on Size of Particle
 Coarse Suspension
 Suspensions having particle sizes of greater
than about 1micron in diameter are called as
coarse suspensions.
 Colloidal Suspension
 Suspensions having particle sizes of suspended
solid less than about 1micron in size are called
as colloidal suspensions.
Flocculated system
 In flocculated system the individual particle are
contact with each other to form loose aggregate &
create network like structure.
 Rate of sedimentation is high.
 Sediment is loosely packed. When shaking it can
be redisperse easily & reform the original
suspension.
 Flocculated suspensions not be elegant because
they are difficult to remove from bottles or vials
& on transferring from the bottle the floccules
remaining sticking to the side of the bottle.
 In deflocculated system the individual particle
Deflocculated system
 In deflocculated system the individual particle
are exist as separate entities.
 Rate of sedimentation is low.
 Sediment is tightly packed. When shaking it
can not be redisperse easily & form the cake.
 Deflocculated suspensions be elegant. They
have pleasing appearance bec. the substance
remain suspended for sufficient long time.
Difference between flocculated and
deflocculated suspension
Flocculated and Deflocculated
FORMULATION OF SUSPENSIONS
 SUSPENSIONS :The three steps that can be
taken to ensure formulation of an elegant
pharmaceutical suspension are:
 1.CONTROL PARTICLE SIZE. On a small
scale, this can be done using a mortar and a
pestle to grind down ingredients to a fine powder.
 2.Use thickening agent to increase viscosity of
the vehicle by using suspending agents or
viscosity increasing agents
 3.Use of a wetting agent/ surfactants
Formulation of Suspensions
 1.Flocculating agents e.g surfactants sodium
lauryl sulphate
 2.Suspending agents e.g
acacia,tragacanth,polymers
 3.Wetting agents e.g Alcohol in tragacanth
mucilage's
 4.Dispersing agents e.g zeta potential
 5.Preservative e.g benzoic acid, sodium
benzoate, methyl paraben & propyle paraben
 6.Organoleptic additives e.g Colors &
sweetening agents etc
SUSPENDING AGENTS:
 Suspending agent are also known as hydrophilic
colloids which form colloidal dispersion.
 Suspending agent form film around particle and
decrease interparticle attraction.
 Most suspending agents perform two functions
i.e. besides acting as a suspending agent they
also imparts viscosity to the solution.
 Sodium alginate, Methylcellulose (1-2%),
Hydroxyethyl cellulose (1-2%), Hydroxypropyl cellulose
(1-2%) Hydroxypropyl methylcellulose (1-2%)
Wetting Agents:
 Hydrophilic materials are easily wetted by water
while hydrophobic materials are not.
 However hydrophobic materials are easily wetted
by non-polar liquids.
 The extent of wetting by water is dependent on
the hydrophillicity of the materials.
 The concentration used is less than 0.5 %.
Surfactants
 Surfactants decrease the interfacial tension between drug
particles and liquid thus liquid is penetrated in the pores of
drug particle displacing air from them and thus ensures
wetting.
 Generally, we use non-ionic surfactants but ionic
surfactants can also be used
 depending upon certain conditions.
 Polysorbate 80 is most widely used due to its
following advantages:
 It is non-ionic so no change in pH of medium.
 No toxicity. Safe for internal use.
Hydrophilic colloids:
 Hydrophilic colloids coat hydrophobic drug
particles in one or more than one layer.
 This will provide hydrophillicity to drug
particles and facilitate wetting
 E.g. acacia, tragacanth, alginates, guar gum.
EQUIPMENT FOR SUSPENSIONS
 1-Mortar and pestle
 It consists of a glass or porcelain mortar and a pestle.
 Advantages:
 (i) Small quantity suspensions can be prepared in the
laboratory.
 (ii) Low cost
 (iii) Simplest operation among all other instruments.
 Disadvantages:
 (i) Generally, the final particle size is considerable larger
then in other
 equipment.
 (ii) It is necessary for the ingredients to have a certain
viscosity prior to Trituration in order to achieve a satisfactory
shear.
Pharmaceutical Applications of
suspensions
 Suspensions Suspensions may be used pharmaceutically
for a number of reasons. Some are given bellow;
 Suspension is usually applicable for drug which is
insoluble or poorly soluble. E.g. Prednisolone
 Suspension To prevent degradation of drug or to improve
stability of drug. E.g. Oxytetracycline suspension
 To mask the taste of bitter or unpleasant drug when
formulated in solution form. Drugs are formulated in as
suspesnion which will be more palatable E.g.
Chloramphenicol palmitate suspension
 Suspension of drug can be formulated for topical
application e.g. Calamine lotion.
Pharmaceutical Applications of
suspensions
 Suspension can be formulated for parentral application in
order to control rate of drug absorption, E.g. penicillin
procaine
 Vaccines as a immunizing agent are often formulated as
suspension.E.g. Cholera vaccine
 X-ray contrast agent are also formulated as suspension.
E.g. Barium sulphate for examination of alimentary tract
 If the drug is unstable when in contact with the vehicle,
suspensions should be prepared immediately prior to
handing out to the patient in order to reduce the amount
time that the drug particles are in contact with the
dispersion medium. Eg Amoxicilin suspension
Pharmaceutical Applications of
Suspensions
 Drugs which degrade in aqueous solution may be
suspended in a non-aqueous phase. eg. Tetracycline
hydrochloride is suspended in a fractionated coconut oil
for ophthalmic use.
 Lotions containing insoluble solids are formulated to
leave a thin coating of medicament on the skin. As the
vehicle evaporates, it gives a cooling effect and leaves
the solid behind.eg calamine lotion and sulphur lotion
compound.
 Bulky, insoluble powders can be formulated as a
suspension so that they are easier to take eg Kaolin or
chalk
ADVANTAGES OF SUSPENSIONS
 Suspension can improve chemical stability of certain
drug. E.g. Procaine penicillin G
 Drug in suspension exhibits higher rate of bioavailability
than other dosage forms. bioavailability is in following
order,
 Solution > Suspension > Capsule >
Compressed Tablet > Coated tablet
 Duration and onset of action can be controlled. E.g.
Protamine Zinc-Insulin suspension Suspension can
mask the unpleasant/ bitter taste of drug. E.g.
Chloramphenicol palmitate
Lecture Suspension.pdf
Lecture Suspension.pdf

Lecture Suspension.pdf

  • 2.
  • 3.
    DEFINITIONS  A Pharmaceuticalsuspension is a disperse system in which internal phase is dispersed uniformly as finely divided insoluble particles throughout the external phase.  The internal phase consisting of insoluble solid particles having a specific range of size which is maintained uniformly throughout the suspending vehicle with aid of single or combination of suspending agent.  The external phase (suspending medium) is generally aqueous in some instance, may be an organic or oily liquid for non oral use.
  • 4.
    DEFINITIONS  Suspension maybe defined as preparation containing finely divided drug particles distributed somewhat uniformly throughout a vehicle in which the drug exhibits a minimum degree of solubility.  Suspensions are the biphasic liquid dosage form of medicaments in which the finely divided solid particles.  The range of solid particles in suspension from 0.5 to 5.0 micron.  Suspensions are used in orally, parentally and also externally.  They are chemically stable than solution.
  • 5.
    DEFINITIONS  The term"Disperse System" refers to a system in which one substance (The Dispersed Phase) is distributed, in discrete units, throughout a second substance (the continuous Phase or vehicle). Each phase can exist in solid, liquid, or gaseous state . . Most suspensions are classified as a coarse suspension which is a dispersion of particles with a mean diameter greater than 1µm (1 to 100 µm. A colloidal suspension is a dispersion of particles with a mean diameter of less than 1µm (0.5µm to 1µm).
  • 6.
    SEDIMENTATION  This isa phenomenon which occurs in dispersed system where the dispersed particles settle to the bottom of the container. This occurs because the particles are too large to remain permanently suspended in the vehicle.  Therefore suitable suspending agents are added to retard this process.
  • 7.
    SUSPENDING AGENTS  Suspendingagents are substances that are used to keep finely divided insoluble materials suspended in a liquid media by preventing there agglomeration (coming together) and by imparting viscosity to the dispersion media so that the particles settle more slowly. Care must be taken when selecting a suspending agent for oral preparations as the acid environment of the stomach may alter the physical characteristics of the suspension and therefore the rate of release of the drug from suspension.  They are various types of suspending agents
  • 8.
    Types of SuspendingAgents  1. NATURAL AGENTS  This class consists of those from. a. Animal source eg Gelatine b. Plant source eg. Accacia, Tragacanth, Starch, sea weed (Alginates) c. mineral sources.eg Bentonite, Kaoline  2. SEMI-SYNTHETIC AGENTS  These consist of substituted cellulos (minerals) eg. Hydroxyethylcellulose , Sodium Carboxymethylcellulose , methylcellulose, Microcrystalline cellulose  3. SYNTHETIC AGENTS  They are synthetic polymers eg carboxypolymethylene (carbopol), Polyvinyl Alcohol, Polyvinyl Pyrolidone iodine complex (PVC).
  • 9.
  • 10.
  • 11.
  • 12.
  • 13.
    Classification of suspensions Based On General Classes I. Oral suspension II. Externally applied suspension III. Parenteral suspension  Based On Proportion Of Solid Particles I. Dilute suspension (2 to10%w/v solid) II. Concentrated suspension (50%w/v solid) Ø Based On Electrokinetic Nature Of Solid Particle I. Flocculated suspension II. Deflocculated suspension  Based On Size Of Solid Particles I. Colloidal suspension (< 1 micron) II. Coarse suspension (>1 micron) III. Nano suspension (10 ng)
  • 14.
    Reasons for suspensions If patient has a difficulty of swallowing solid dosage forms (a need for oral liquid dosage form).  Faster rate of dissolution and oral absorption than solid dosage forms, yet slower than solutions.  Drugs that have very low solubility are usefully formulated as suspensions.  Drugs that have an unpleasant taste in their soluble forms (e.g., chloramphenicol (soluble) vs. chloramphenicol palmitate (insoluble )).
  • 15.
    Based on GeneralClass  Oral Suspension e.g. Paracetamol Suspension  Externally Applied suspension e.g. Calamine lotion  Parenteral Suspension e.g. Insulin zinc suspension
  • 16.
    Based on Proportionof Solid Particles  Dilute Suspension (2 to 10% w/v solid) e.g. cortisone acetate, predinsolone acetate  Concentrated Suspension (50% w/v solid) e.g. Zinc oxide suspension  BASED ON ELECTROKINETIC NATURE OF SOLID PARTICLE  Flocculated Suspension  Deflocculated Suspension
  • 17.
    Based on Sizeof Particle  Coarse Suspension  Suspensions having particle sizes of greater than about 1micron in diameter are called as coarse suspensions.  Colloidal Suspension  Suspensions having particle sizes of suspended solid less than about 1micron in size are called as colloidal suspensions.
  • 18.
    Flocculated system  Inflocculated system the individual particle are contact with each other to form loose aggregate & create network like structure.  Rate of sedimentation is high.  Sediment is loosely packed. When shaking it can be redisperse easily & reform the original suspension.  Flocculated suspensions not be elegant because they are difficult to remove from bottles or vials & on transferring from the bottle the floccules remaining sticking to the side of the bottle.  In deflocculated system the individual particle
  • 19.
    Deflocculated system  Indeflocculated system the individual particle are exist as separate entities.  Rate of sedimentation is low.  Sediment is tightly packed. When shaking it can not be redisperse easily & form the cake.  Deflocculated suspensions be elegant. They have pleasing appearance bec. the substance remain suspended for sufficient long time.
  • 20.
    Difference between flocculatedand deflocculated suspension
  • 21.
  • 23.
    FORMULATION OF SUSPENSIONS SUSPENSIONS :The three steps that can be taken to ensure formulation of an elegant pharmaceutical suspension are:  1.CONTROL PARTICLE SIZE. On a small scale, this can be done using a mortar and a pestle to grind down ingredients to a fine powder.  2.Use thickening agent to increase viscosity of the vehicle by using suspending agents or viscosity increasing agents  3.Use of a wetting agent/ surfactants
  • 24.
    Formulation of Suspensions 1.Flocculating agents e.g surfactants sodium lauryl sulphate  2.Suspending agents e.g acacia,tragacanth,polymers  3.Wetting agents e.g Alcohol in tragacanth mucilage's  4.Dispersing agents e.g zeta potential  5.Preservative e.g benzoic acid, sodium benzoate, methyl paraben & propyle paraben  6.Organoleptic additives e.g Colors & sweetening agents etc
  • 25.
    SUSPENDING AGENTS:  Suspendingagent are also known as hydrophilic colloids which form colloidal dispersion.  Suspending agent form film around particle and decrease interparticle attraction.  Most suspending agents perform two functions i.e. besides acting as a suspending agent they also imparts viscosity to the solution.  Sodium alginate, Methylcellulose (1-2%), Hydroxyethyl cellulose (1-2%), Hydroxypropyl cellulose (1-2%) Hydroxypropyl methylcellulose (1-2%)
  • 26.
    Wetting Agents:  Hydrophilicmaterials are easily wetted by water while hydrophobic materials are not.  However hydrophobic materials are easily wetted by non-polar liquids.  The extent of wetting by water is dependent on the hydrophillicity of the materials.  The concentration used is less than 0.5 %.
  • 27.
    Surfactants  Surfactants decreasethe interfacial tension between drug particles and liquid thus liquid is penetrated in the pores of drug particle displacing air from them and thus ensures wetting.  Generally, we use non-ionic surfactants but ionic surfactants can also be used  depending upon certain conditions.  Polysorbate 80 is most widely used due to its following advantages:  It is non-ionic so no change in pH of medium.  No toxicity. Safe for internal use.
  • 28.
    Hydrophilic colloids:  Hydrophiliccolloids coat hydrophobic drug particles in one or more than one layer.  This will provide hydrophillicity to drug particles and facilitate wetting  E.g. acacia, tragacanth, alginates, guar gum.
  • 29.
    EQUIPMENT FOR SUSPENSIONS 1-Mortar and pestle  It consists of a glass or porcelain mortar and a pestle.  Advantages:  (i) Small quantity suspensions can be prepared in the laboratory.  (ii) Low cost  (iii) Simplest operation among all other instruments.  Disadvantages:  (i) Generally, the final particle size is considerable larger then in other  equipment.  (ii) It is necessary for the ingredients to have a certain viscosity prior to Trituration in order to achieve a satisfactory shear.
  • 30.
    Pharmaceutical Applications of suspensions Suspensions Suspensions may be used pharmaceutically for a number of reasons. Some are given bellow;  Suspension is usually applicable for drug which is insoluble or poorly soluble. E.g. Prednisolone  Suspension To prevent degradation of drug or to improve stability of drug. E.g. Oxytetracycline suspension  To mask the taste of bitter or unpleasant drug when formulated in solution form. Drugs are formulated in as suspesnion which will be more palatable E.g. Chloramphenicol palmitate suspension  Suspension of drug can be formulated for topical application e.g. Calamine lotion.
  • 31.
    Pharmaceutical Applications of suspensions Suspension can be formulated for parentral application in order to control rate of drug absorption, E.g. penicillin procaine  Vaccines as a immunizing agent are often formulated as suspension.E.g. Cholera vaccine  X-ray contrast agent are also formulated as suspension. E.g. Barium sulphate for examination of alimentary tract  If the drug is unstable when in contact with the vehicle, suspensions should be prepared immediately prior to handing out to the patient in order to reduce the amount time that the drug particles are in contact with the dispersion medium. Eg Amoxicilin suspension
  • 32.
    Pharmaceutical Applications of Suspensions Drugs which degrade in aqueous solution may be suspended in a non-aqueous phase. eg. Tetracycline hydrochloride is suspended in a fractionated coconut oil for ophthalmic use.  Lotions containing insoluble solids are formulated to leave a thin coating of medicament on the skin. As the vehicle evaporates, it gives a cooling effect and leaves the solid behind.eg calamine lotion and sulphur lotion compound.  Bulky, insoluble powders can be formulated as a suspension so that they are easier to take eg Kaolin or chalk
  • 33.
    ADVANTAGES OF SUSPENSIONS Suspension can improve chemical stability of certain drug. E.g. Procaine penicillin G  Drug in suspension exhibits higher rate of bioavailability than other dosage forms. bioavailability is in following order,  Solution > Suspension > Capsule > Compressed Tablet > Coated tablet  Duration and onset of action can be controlled. E.g. Protamine Zinc-Insulin suspension Suspension can mask the unpleasant/ bitter taste of drug. E.g. Chloramphenicol palmitate