The Biphasic Dosage form : Suspensions


  • A suspension is biphasic system in which a dispersed state is solid while continuous phase is liquid (oily/aqueous), the system is stabilized by addition of “Suspending agent.”
  • Most pharmaceutical suspensions are aqueous in nature.


  • Suspensions offer distinct advantages they are as follows:
1. Stability:
  • Some drugs are not stable in solution form.
  • In such cases it is necessary to prepare an insoluble form of that drug.
  • Therefore drugs are administered in the form of suspension.
  • e.g. Procaine Penicillin G.
2. Choice of solvent:
  • If the drug is not soluble in water and solvents other than water are not acceptable, suspension is the only choice.
  • e.g. Parenteral corticosteroid.
3. Mask the taste;
  • In some cases drugs are made insoluble and dispensed in the form of suspension to mask the objectionable taste.
  • e.g. Chloramphenicol base is very bitter in taste, hence the insoluble chloramphenicol palmitate is used which does not have the bitter taste
4. Prolonged action:
  • Suspension has a sustaining effect, because, before absorption the solid particles should be dissolved.
  • This takes some time. e.g. Protamine Zinc Insulin and Procaine Penicillin G.
5. Bioavailability:
  • Drugs in suspension exhibit a higher bioavailability compared to other dosage forms (except solution) due to its large surface area, higher dissolution rate.
  • e.g. Antacid suspensions provides immediate relief from hyperacidity than its tablet chewable tablet form.

Types of suspensions

  • The pharmaceutical suspension preparations are differentiated into suspensions, mixtures, magmas, gels and lotions.


  • Simple suspension is the insoluble solid dispersed in a liquid.
  • The stability considerations suggest that the manufacture of drugs in dry form is ideal.
  • They are reconstituted as suspensions using a suitable vehicle before administration.
Few examples are:
i) Dispersible tablets of antibiotic, Amoxicillin (e.g. NovaMOX)
ii) Procaine penicillin G powder (E.G. PENIDURE)


  • Gels are semisolid systems consisting of small inorganic particles suspended in a liquid medium.
  • It consists of a network of small discrete particles.
  • It is a two-phase system.
  • e.g. Aluminum hydroxide gel.


  • Lotions are suspensions which are intended to be applied to the unbroken skin without friction.
  • e.g. Calamine lotion, Hydrocortisone lotion.

Magmas and Milks

  • Magmas and milk are aqueous suspensions of insoluble, inorganic drugs and differ from gels mainly in that the suspended particles are larger.
  • When prepared they are thick and viscous and because of this, there is no need to add a suspending agent.
  • e.g. Bentonite magma, Milk of Magnesia.


  • Mixtures are oral liquids containing one or more active ingredients, dissolved, suspended or dispersed in a suitable vehicle.
  • Suspended solids may separate slowly on standing, but are easily redispersed on shaking.
  • e.g. Kaolin mixture with pectin.

Classification of suspensions

  • Based on the proportion of solids, suspensions are empirically classified as dilute or concentrated systems.

i) Dilute suspensions :

  • Solid content 2 - 10 % e.g. Cortisone acetate and Prednisolone acetate suspension.

ii) Concentrated suspensions

  • Solid content 10 - 50 % e.g. Zinc oxide suspension for external use, Procaine penicillin G injection, Antacid suspension etc.
Depending on the nature and behavior of solids, suspensions are classified as flocculated and deflocculated.

Deflocculated suspension

  • In this system, solids are present as individual particles.

Flocculated suspension

  • In this system, particles aggregate themselves by physical bridging.
  • These flocs are light, fluffy conglomerate which are held together by weak van der Waal’s forces of attraction.
  • The difference between Flocculated and Deflocculated Suspensions is as follows,

  • Deflocculated System

    Flocculated System

    i)        Pleasant appearance, because of uniform dispersion of particles.
    ii)      Supernatant remains cloudy.
    iii)    Particles exist as separate entities
    iv)    Rate of sedimentation is slow, as the size of particles are small.
    v)      Particles settle independently and separately

    vi)    The sedimentation is closely packed and form a hard cake.
    vii)  The hard cake cannot be redispersed.
    viii)Bioavailability is higher due to large specific surface area.

    i)        Somewhat unsightly sediment.

    ii)      Supernatant is clear
    iii)    Particles form loose aggregates.
    iv)    Rate is high, as flocs are the collection of smaller particles having a larger size.
    v)      Particles settle as flocs.

    vi)    Sediment is a loosely packed network and hard cake cannot form.
    vii)  The sediment is easy to redisperse.
    viii)Bioavailability is comparatively less due to small specific surface area.

Factors affecting the stability of a suspension:

  • Settling in suspensions

Brownian movement:

  • Brownian movement of particles prevents sedimentation.
  • In general, particles are not in a state of Brownian motion in pharmaceutical suspensions, due to,
i) larger particle size (Brownian movement is seen in particles having diameter of about 2 to 5 mm (depending on the density of the particles and the viscosity and the density of the suspending medium.
ii) and higher viscosity of the medium.


  • The rate of sedimentation of particles can be expressed by the Stoke’s law, using the following formula:
    Where ,
    d is the particle diameter
    Ps, Pl are densities of a particle and liquid respectively.
    g is the acceleration of gravity.
    n is the viscosity of the medium.
  • Stock’s law is applicable if:

i) particles are spherical; but particles in the suspension are largely irregular.
ii) Particles settle freely and independently.
  • In suspensions containing 0.5 - 2 % (w/v) solid, the particles do not interfere with each other during sedimentation - hence free settling occurs.
  • Most pharmaceutical suspensions contain 5 - 10 % or higher percentages of solid. in this cases particles interfere with one another as they fall - hence hindered settling occurs and Stoke’s law no longer applies.
  • Stoke’s law is applicable to deflocculated systems, because particles settle independently.
  • However, this law is useful in a qualitative manner in fixing factors which can be utilized in formulation of suspensions.

1. Particle size:

  • Rate of sedimentation is directly proportional to “(diameter of particle)2”
  • So smaller the particle size more stable the suspension.
  • The particle-particle interaction results in the formation of floccules or coagules where the sedimentation rate increases.
  • The particles are made fine either by dry milling prior to suspension or wet-milling of the final suspension in a colloid mill or a homogenizer.

2. Viscosity of the medium

  • According to Stoke’s law:
  • Rate of sedimentation is inversely proportional to the viscosity of medium.
  • Viscosity of the suspension should be optimum.
  • Viscosity can be increased by adding suspending agents or thickening agents.
  • Selection of high viscosity have both advantages and disadvantages.
i) Sedimentation rate is retarded, hence enhances the physical stability of the suspension.
ii) Inhibits crystal growth, because movement of particles is diminished.
iii) Prevents the transformation of metastable crystals to stable crystals.
i) Redispersibility of the suspension on shaking is difficult.
ii) Pouring out of the suspension from the container may be difficult.
iii) Creates problems in the handling of materials during manufacture.
iv) May retard absorption of drugs from the suspension.

3. Density:

  • Rate of sedimentation is directly proportional to the differences of densities of solids and liquids. (density of solid - density of liquid medium).
  • Lesser the difference between the densities of solid particles and liquid medium slower is the rate of sedimentation.
  • Since it is very difficult to change the absolute density of the solid particles so the density of the liquid medium can be manipulated by changing the composition of the medium.
  • The addition of nonionic substances such as sorbitol, polyvinylpyrrolidone (PVP), glycerin, sugar, or one of the polyethyleneglycols or combination of these may be helpful in the manipulation.
  • If the density of the particles is greater than the continuous medium the particles will settle downwards, the phenomenon is known as sedimentation.
  • If the density of particle is lesser than that of the liquid medium then the particles will move upward - the phenomenon is known as creaming.

Formulation of suspensions:

  • The product must,
1) Flow readily from the container
2) Possesses a uniform distribution of particles in each dose.
  • Two approaches are commonly employed to secure the two requirements,
(i) The use of structured vehicle to maintain deflocculated particles in suspension.
  • Structured vehicles are pseudoplastic and plastic in nature; it is frequently desirable that thixotropy be associated with these two type of flow.
  • Structured vehicles act by entrapping the particles so that, ideally no settling occurs.
  • In reality some degree of sedimentation will usually take place.
  • The shear thinning property of these vehicle does however facilitate the redispersion when shear is applied.
(ii) Application of the principles of flocculation to produce flocs that, although, they settle rapidly are easily redispersed with a minimum of agitation.

Preparation of suspensions

  • Method of preparations can be subdivided into two broad categories:

1) Precipitation method:

  • There are three methods
1. organic solvent precipitation
2. precipitation effected by changing the pH of the medium and
3. double decomposition
(i) Organic solvent precipitation:
  • Water insoluble drugs can be precipitated by dissolving them in water-miscible organic solvents (e.g. alcohol, acetone, propylene glycol and polyethylene glycol) and then adding the organic phase to distilled water under standard conditions produces a suspension having a particle size in the 1 to 5 mm range.
  • Example: Prednisolone is precipitated from a methanolic solution to produce a suspension in water.
  • Disadvantage: Harmful organic solvents may be difficult to remove.
  • Advantage: In case of parenteral or inhalation therapy very fine particles are required, which can be prepared by this method.
(ii) Precipitation effected by changing the pH of the medium:
  • A drug may be readily soluble at a certain pH and precipitate at another pH.
  • This type of drug is first dissolved in the favorable pH and then the solution is poured in another buffer system to change the pH of the medium and the drug will form a suspension in the medium of the second pH.
  • Example 1: Estradiol suspensions can be prepared by changing the pH of the of its aqueous solution; estradiol is readily soluble in alkali as potassium or sodium hydroxide solutions. If a concentrated solution of estradiol is thus prepared and added to a weakly acidic solution of hydrochloric, citric or acetic acids, under proper conditions of agitation, the estradiol is precipitated in a fine state of subdivision.
  • Example 2: Insulin suspension may also be prepared by pH change method. Insulin has an isoelectric point of approximately pH5. When it is mixed with a basic protein, such as protamine, it is readily precipitated when pH is between the isoelectric points of the two components, i.e. pH 6.9 to 7.3. Protamine-Zinc-Insulin (PZI) contains an excessive quantity of zinc to retard the rate of absorption. According to the British Pharmacopoeia phosphate buffer is added to an acidified solution of PZI so that the pH is between 6.9 to 7.3 to form the suspension.
(iii) Double decomposition method
  • In this method two water soluble reagent forms a water insoluble product.
  • Example: White Lotion NF is prepared by slowly adding zinc sulfate solution in a solution of sulphurated potash to form a precipitate of zinc polysulphide.

2) Dispersion method:

  • In this cases the powder form of the drug is directly dispersed in the liquid medium.
  • The liquid medium should have good power of wetting the powder.
1. Small scale preparation method:
  • A suspension is prepared on the small scale by grinding or levigating the insoluble material in the mortar to a smooth paste with a vehicle containing the dispersion stabilizer and gradually adding the remainder of the liquid phase in which any soluble drugs may be dissolved.
  • The slurry is transferred to a graduate, the mortar is rinsed with successive portions of the dispersion medium is finally brought to the final volume.
2. Large scale preparation method:
  • On large scale dispersion method the solid particles are suspended using ball, pebble and colloid mills.
  • Dough mixers, pony mixers and similar apparatus are also employed.

Evaluation of Suspension Stability:

  • Prepared suspensions are evaluated by using following criterias,
  1. Sedimentation Volume.
  2. Degree of Flocculation.
  3. Redispersibility.
  4. Rehologic Methods.
  5. Particle Size Changes.

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