Contents

·      Definition

·      Size Classification of Suspensions

·      Routes of Administration

·      Forces In a Suspension

·      Pharmaceutical applications of suspensions

·      Qualities of ideal suspension

·      Factors  to Be Considered

·      Method of preparation

 


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Definition


A suspension is a two phased system in which a finely divided solid is dispersed in a continuous phase of solid, liquid, or gas. The undissolved solid exists in equilibrium with a saturated solution of the solid in the continuous phase.

A pharmaceutical suspension is acoarse dispersion in which insoluble solid particles are dispersed in a liquid medium.




Size Classification of Suspensions


A pharmaceutical suspension is a coarse dispersion in which insoluble solid particles are suspended in a liquid medium.

A coarse suspension is a dispersion of finely divided, insoluble solid particles (the disperse phase) in a liquid (the dispersion medium). Most pharmaceutical suspensions consist of an aqueous dispersion medium although in some instances it may be an organic or oily liquid. A disperse phase with a mean diameter of up to 1 mm is usually termed a colloidal dispersion and include such examples as aluminum hydroxide and magnesium hydroxide suspensions.

A solid in liquid dispersion in which the particles are above colloidal size is termed a coarse suspension.




Routes of Administration

        

  • Oral
  • Parenteral
  • Topical (lotions)

Forces In a Suspension


  • Gravitational
  • Interfacial  
  • Interparticulate


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Pharmaceutical applications of suspensions



1)    Insoluble drug or poorly soluble drugs which required to be given orally in liquid dosage forms ( in case of children, elderly, and patients have difficulty in swallowing solids dosage forms)

2)    To over come the instability of certain drug in aqueous solution:

a.     Insoluble derivative formulated as suspension

b.     Reduce the contact time between solid drug particles and dispersion media Þ increase the stability of drug like Ampicillin by making it as reconstituted powder.

c.      A drug that degraded in the presence of water Þ suspended in non-aqueous vehicles. Examples are phenoxymethypencillin/ coconut oil   and tetracyclineHCL/ oil

3)     To mask the taste: 

Examples are paracetamol suspension (more palatable) and chloramphenicol palmitate.

4)    Some materials are needed to be present as finely divided forms to increase the surface area. Fore example, Mg carbonate and Mg trisilcate are used to adsorb some toxins

5)    Suspension can be used topical applications:

An example is calamine lotion BpÞ after evaporation of dispersing media; the active agent will be left as light deposit

6)    Can be used for parentral administration Þ intramuscular (i.m.) to control arte of absorption 

7)    In vaccines

8)    X-ray contrast media: an example is oral and rectal administration of propyliodone

9)    In aerosol Þ suspension of active agents in mixture  of propellants


 

Qualities of ideal suspension


A well-formulated suspension should have the following properties:

1)The dispersed particles should not settle readily and the settle should redispersed immediately on shacking. Ideally, the particles in a suspension should not sediment at any time during the storage period. Unfortunately, the present technology does not allow us to prepare such a suspension. Since one cannot completely avoid the sedimentation of particles, it is desirable that the particles should settle slowly. The easy redispersion of sedimented particles in a suspension is important for the uniformity of dose.

2)The particle should not form a cake on settling

3)The viscosity should be such that the preparation can be easily poured. A highly viscous suspension would make pouring difficult.

4)It should be chemically and physically stable

5)It should be palatable (orally)

6)It should be free from gritting particles (external use)

 

Factors  to Be Considered


 

*Wetting of the particles: It is difficult to disperse solid particles in a liquid vehicle due to the layer of adsorbed air on the surface. Thus, the particles, even high density, float on the surface of the liquid until the layer of air is displaced completely. The use of wetting agent allows removing this air from the surface and to easy penetration of the vehicle into the pores. Alcohol, glycerin, and propylene glycol are frequently used to remove adsorbed air from the surface of particles when aqueous vehicle is used to disperse the solids. When the particles are dispersed in a non-aqueous vehicle, mineral oil is used as wetting agent. Irrespective of the method of preparation, the solid particles must be wetted using any of the suitable wetting agents before the dispersion in the vehicle.

       Solid particles that are not easily wetted by aqueous vehicle after the removable of the adsorbed air are referred to as hydrophobic particles. It is necessary to reduce the interfacial tension between the particles and the vehicle by using surface-active agents to improve the wettibility. Sodium lauryl sulfate is one of the most commonly used surface-active agents. Hydrophilic particles are easy to disperse in the aqueous vehicle once the adsorbed air is removed. Hydrophilic particles do not require the use of surface-active agents.

·        The main function of wetting agents: (1)- to reduce the contact angle between surface of solid particles and wetting liquid via displace the air in the voids (2)- surfactant

·        Examples of wetting agents are tragcanth mucilage, glycerin, glycols, bentonite and polysorbates.

·        Excessive amounts of wetting agents can cause foaming or undesirable taste or odor.

·        Contact angle can be used to measure wettibility, if the angle approximately equal or more than 90 0, particles are floating well out of fluid.

Particle size:Particle size of any suspension is critical and must be reduced within the range as determined during the preformulation study.

·         Too large or too small particles should be avoided. Larger particles will settle faster at the bottom of the container and too fine particles will easily form hard cake at the bottom of the container.

·        The particle size can be reduced by using mortar and pastel but in large-scale preparation different milling and pulverization equipments are used.

·        Limitation in particle size reduction (after reaching a certain particle size):

1.     Expensive and time consuming

2.     Movement of small particles due to brownian motion cause particles to aggregate, settle, form hard cake that it is difficult to redispersed 

Electrokinetic Properties:Dispersed solid particles in a suspension may have charge in relation to their surrounding vehicle. These solid particles may become charged through one of two situations.

1.     Selective adsorption of a particular ionic species present in the vehicle. This may be due to the addition of some ionic species in a polar solvent. Consider a solid particle in contact with an electrolyte solution. The particle may become positively or negatively charged by selective adsorption of either cations or anions from the solution.

2.     Ionization of functional group of the particle. In this situation, the total charge is a function of the pH of the surrounding vehicle.

 


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Method of preparation


The preparation of suspension includes three methods:


1.     use of controlled flocculation

2.      use of structured vehicle

3.     combination of both of the two pervious methods.


1.Controlled flocculation Controlled flocculation of particles is obtained by adding flocculating agents, which are (1)-electrolytes (2)- surfactants (3)- polymers

·        1-Addition of electrolyte to control flocculation

·        Most frequently used flocculating agents are electrolytes, which reduce the zeta potential surrounding the solid particles. This leads to decrease in repulsion potential and makes the particle come together to from loosely arrange structure (floccules).

·        The flocculating power increases with the valency of the ions. As for example, calcium ions are more powerful than sodium ions because the velency of calcium is two whereas sodium has valency of one.

·        The following figure shows the flocculation of a bismuth subnitrate suspension by means of monobasic potassium phosphate (flocculating agents).

2-Addition of surfactant to control flocculation

·        Both ionic and non-ionic surfactants could be used to control flocculation

·        Surfactant adsorbed on the surface of solid particle leading to neutralization or reversing the surface charge

o   Since most of surfactants act as wetting agents and flocculating agents, the amount of surfactant to be added should be calculated based on this fact

3- Addition of polymers to control flocculation

·        Polymers are long-chained, high molecular-weight compounds containing active groups spaced along their length.

·        These agents promote flocculation through adsorption of part of the chain on the surface of particle and the remaining part project out into the dispersion medium. Formation of bridge between the projected parts leads to formation of floccules

·        Hydrophilic polymers also act as protective colloids resulting in coated particles have fewer tendencies to form cake.

·        Polymers exhibits pseudoplastic flow in solution that promotes the physical stability of suspension

·        Some polymers like gelatin stabilize the suspension based on the pH and ionic strength of dispersion medium (carry charge)

·        An example of polymer is xanthan gum

·        Positively charged Liposomes (vesicles of phospholipids) adsorbed on negatively charged particles to prevent caking formation.

2-Structured vehicle   Structured vehicles called also thickening or suspending agents. They are aqueous solutions of natural and synthetic gums. These are used to increase the viscosity of the suspension.

·        Methyl cellulose, carboxymethyl cellulose, sodium carboxymethyl cellulose, acacia, gelatin and tragacanth are the most commonly used structured vehicle in the pharmaceutical suspensions. These are non-toxic, pharmacologically inert, and compatible with a wide range of active and inactive ingredients.

·        These structured vehicles entrapped the particle and reduces the sedimentation of particles. Although, these structured vehicles reduces the sedimentation of particles, not necessarily completely eliminate the particle settling. Thus, the use of deflocculated particles in a structure vehicle may form solid hard cake upon long storage.

·        The risk of caking may be eliminated by forming flocculated particles in a structured vehicle.

·        Note that too high viscosity isn’t desirable and it causes difficulty in pouring and administration. Also, it may affect drug absorption since they adsorb on the surface of particle and suppress the dissolution rate.

·        Structured vehicles are pseudoplastic or plastic in their rheological behaviors

 



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