Digitally signed by Fahad Hussain DN: cn=Fahad Hussain, o=PharmaMirror, ou, email=pharmamirror@gmail.com, c=BD Date: 2011.04.

29 09:32:01 +06'00'

STABILITY PROBLEMS OF EMULSION EMULSION Emulsion may be defined as a biphasic system consisting of two immiscible liquids usually water and oil, one of which is finely subdivided and uniformly dispersed as droplets throughout the other. Since such a system is thermodynamically, a suitable emulsifying agent is required to stabilize the system. It has two phases i. oil phase ii. water phase In other way i. External phase ii. Internal phase

Instability of an emulsion: Various deviations from ideal behavior of an acceptable emulsion is known as its instability. The signs of instability are 1. Flocculation or coagulation 2. Creaming 3. Coalescence 4. Breaking or cracking 5. Phase inversion 6. Deterioration by micro-organism 7. Miscellaneous physical and chemical changes. Flocculation: Flocculation is the joining together of globules to form large clumps or floccules within the emulsion. In flocculation the interfacial film and the individual droplets remain intact the globules do not coalesce and may be redispersed by shaking. Cause: Flocculation depends on the electrical potential on the surface of the droplets. There is a high repulsive force among the dispersed globules. If the repulsive force is decreased the globules tend to aggregate. The lowering of repulsive force may be caused i. when the used emulsifying agent is insufficient ii. when the volume of the internal phase is high Remedy: The presence of high charged density on the dispersed droplets will ensure the presence of a high energy barrier and these reduce the incidence of flocculation. Creaming: Creaming is the rising or settling of dispersed globules to form a concentrated layer at the surface or at the bottom of the emulsion.

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FACTORS AFFECTING THE STABILITY OF AN EMULSION Particle size: Increased particle size of the internal phase causes the decreased stability of an emulsion. Smaller size of the particles of internal phase is always preferable. Particle-particle interaction: Deflocculated particles are always preferable because the less the particleparticle interaction the more the stability of an emulsion. Particle density: The less the particle density the more the stability of an emulsion. Bulk phase/external phase density: the more the bulk phase density the more the stability of an emulsion. Bulk phase viscosity: Generally the more the viscosity of bulk phases the more the stability of emulsion.

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The phase which makes globules or droplets is known as internal phase or disperse phase and other is external or continuous phase. Oil can be present as internal and external phase and water also as internal or external phase. Emulsion is normally opaque. Particle sizes of emulsion are from 0.1 to 100 m. It can be used orally, topically and parentally.

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Cause: Creaming is influenced by gravity on the globules. So it depends on the sedimentation or creaming rate. This rate depends i. diameter of the dispersed globules ii. Viscosity of the dispersion medium iii. Density difference between two phases Creaming of emulsion can be explained by stokes law 2r2 (d1-d2)g D2 (d1-d2)g V=-----------------------V=-----------------------18 9 Where V= rate of creaming r= particle radius in cm D =particle diameter in cm d1=density of the internal phase d2=density of the external phase g= gravitational constant = viscosity of the external phase From the equation we can say i. Increase diameter of globules increases the velocity and vice versa. ii. Increase viscosity of the dispersion medium decreases the velocity and vice versa. iii. If d1>d2- downward creaming d1<d2- upward creaming d1=d2- No creaming Remedy: i. Reduction of the globules size by using an efficient homogenizer. ii. Increasing the viscosity of the continuous phase by using viscosity imparting agent. iii. By reducing the density difference between two phases. iv. By controlling the dispersed phase concentration. v. By storing in a cool place or low temperature.

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Coalescence: Coalescence is the fusing of the globules into larger drop or drops. In coalescence the globules lose their individuality. During fusion the interfacial film is destroyed. So coalescence is irreversible. Globules can not be redistributed by shaking. Cause: Coalescence depends on the structural properties of the interfacial film. So it occurs when emulsifying agent loses its activity or the amount of emulsifying is insufficient. Remedy: i. By adding sufficient amount of emulsifying agent and passing the product through the proper emulsifying machinery. ii. During preparation the addition of emulsifying agent should be appropriate because the use of wrong emulsifying agent loses its activity within a short period of time. Breaking or Cracking: This involves coalescence of the dispersed globules and separation of the dispersed phase as a separate layer. Redispersion can not be achieved by shaking and therefore the advantages of emulsification are lost and accurate dosage form is impossible. Cause: Cracking may be caused any physical or biological or chemical effect that changes the nature of the interfacial film of an emulsifying agent. The physical factors causing breaking are described below. i. Opposite types of emulsifying agent: Addition of an emulsifying agent of opposite type tends to decrease the power of emulsification which cause cracking. Example: Soaps of monovalent metals (Sodium lauryl sulphate) produce o/w emulsion while soaps of divalent metals (Calcium lauryl sulphate) produce w/o emulsion. Addition of

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ii. iii.

iv. v. vi. Remedy: i. ii. iii. iv.

monovalent soap to a divalent soap emulsion or a divalent soap to a monovalent soap emulsion leads to instability or cracking. Addition of common solvent: Addition of a solvent in which both disperse and continuous phase are soluble forms a single phase system. Temperature: An increase in temperature may coagulate certain types of macromolecular emulsifier which are protein in nature cause instability of an emulsion. An increase in temperature will increase the number of collision between globules that are effective in overcoming the barrier to coalescence and instability of an emulsion. Freezing: If an emulsion is kept below 40C the aqueous phase will turn into ice. These ice crystals will press on oil phase. As a result cracking will occur. Incorporation of excess disperse phase: Emulsion with a disperse phase concentration in excess of 74% has a marked tendency to crack. Addition of insufficient amount of emulsifying agent. By incorporating more emulsifying agent. By controlling the temperature at which emulsion is kept. By controlling disperse phase concentration. By adding correct emulsifying agent.

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Deterioration by micro-organism: Mold, yeast and bacteria may a. Bring about the decomposition of the emulsifier. b. Contaminate the aqueous phase. c. Destroy oil soluble vitamins. Remedy: Add chemical agent that will act specially as preservative. Combination of para-hydroxy benzoates 0.1% to 2% of methyl ester and 0.02% to 0.05% of propyl ester are frequently used for this purpose. Preservative should be adequately soluble in both phases. If not more than one type of preservatives should be used one for oil phase and other for aqueous phase. The emulsifying agent and other ingredients of the formulation should not form complex with the preservatives. Miscellaneous: Care must be taken to protect emulsion against deterioration caused by light, temperature and freezing and thawing. STABILITY PROBLEMS OF SUSPENSION The ideal characteristics of a suspension are 1. The sedimentation is less as possible 2. The sediment is redispersible According to strokes law The rate of sedimentation of a particle in a liquid medium is Directly proportional to the diameter of the particle Directly proportional to the density difference between particle and medium Inversely proportional to the viscosity of the medium. Mathematical expression 2r2 (d1-d2)g V=-----------------------9

D2 (d1-d2)g V=-----------------------18

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Phase inversion: An emulsion is said to invert when it changes from an o/w to a w/o emulsion and vice versa. Inversion is mainly brought about by chemical degradation. But there is some effect of physical factor i. By changing the phase volume ratio. ii. By cooling the emulsion specially those which are prepared by heating and mixing of two phases.

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Where, V= velocity of sedimentation in cm/sec r= particle radius in cm D= particle diameter in cm d1=density of the particle in gm/cc d2=density of the medium in gm/cc g= gravitational constant =980cm/sec2 = viscosity of the medium. The characteristics of a suspension are that the particles of the suspension are more or less settle down on keeping for sometime. But the rate of sedimentation is different for different suspension. Problems associated with suspension preparation 1. Caking and poor redispersibility 2. Cap locking 3. Color change 4. Crystal growth 5. Deflocculation 6. Decrease in drug potency 7. Change in flavor 8. PH change 9. Change in viscosity 10. Rapid settling 11. Change in particle size 12. Microbial growth 13. Foaming 14. Chemical interaction 15. Dispersion of hydrophobic drug

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Caking and poor redispersibility Caking is a compact mass of insoluble solids particle formed generally in deflocculated suspension. Cause: Due to the smaller size of the particle, the rate of sedimentation of deflocculated suspension is very slow. The sediment eventually comes very close packed, owing to the weight of the upper layers of the sediment materials. Due to the particle-particle interaction, the repulsive forces between particles are overcome and a hard cake is formed which is difficult to redisperse. Remedy: a. By using flocculating agent: flocculating agents prevent cake formation by the flocculation of the particles. The process of flocculation as well as the stabilization of the suspension are mentioned below: The particles, irrespective of their charge are coated with positively charged agent. The particles are flocculated by the use of a negatively charged agent to bring the product in to the non caking zone. Finally a minimum amount of the desired suspending agent or mixture of suspending agents is added and the suspension is again observed for optimum flocculation and freedom from caking. Examples of flocculating agents: Electrolytes, Surfactants, polymers b. By using viscosity imparting agent:

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Cake formation is due to the sedimentation of the particles. The greater is the viscosity of the liquid, the less is the rate of sedimentation and less is the cake formation. So we can prevent the cake formation using viscosity imparting agents. Examples : Acacia, Tragacanth, Agar c. Caking is prevented by controlling of pH of the dispersion phase. d. It can be controlled by decreasing particle size. Cap Locking Cause Caplocking is a filling problem which occurs when the dispersed particles crystallize on the threads of the bottle cap and interface in cap removal. Remedy Caplocking can be prevented by using different vehicle containing sucrose, glucose, sorbital and glycerine. Color change: Cause: Light sensitive color may be changed in presence of light. Due to the increased in surface area some color may be changed. Remedy: By keeping the bottle in dark place.

Deflocculation: Cause:

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Remedy: By using flocculating agent Electrolytes Detergents Polymer Decrease in drug potency: Cause: Change in flavor: Cause:

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Remedy:

By adding surfactants By controlling solubility By Controlling pH By preventing temperature fluctuation

Change in pH Adding of excess electrolytes. Due to drug degradation.

Due to decomposition of the drug. Due to the change in particle size By keeping suspension for long time.

Flavoring agents are volatile compounds. So the flavor of the suspension may be changed on long term use. Remedy:

Crystal growth: Cause: There is always a degree of crystal growth which mainly occurs in storage condition due to Temperature fluctuation pH change Impurity Low solubility

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 pH Change: Causes:

By using sufficient flavoring agents.

Drug degradation Alkalinity of glass bottle. Microbial growth

Remedy: By adding buffering agents. Buffering agents help to maintain chemical stability also ensure physiological compatibility. Change in viscosity: The viscosity of the suspension may be changed on long term use. Remedy: By using sufficient viscosity imparting agents. Rapid settling: Some times rapid settling of particles is found in suspension. Remedy: By decreasing the particle size. By using viscosity imparting agents.

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Chemical interaction: Chemical interaction may be arisen during the addition of additives to the drug such as cationic surfactants react with any anionic ingredients. Remedy: Care should be taken when additive added to the drug. Dispersion of hydrophobic drugs: Hydrophobic drug particles do not dissolve in water. So suspension of hydrophobic drug creates some problem in particle dispersion. Remedy: Wetting agents are used in this concern which promotes the dispersion of hydrophobic drug in water. Examples of wetting agents: Surfactants Sodium carboxy methyl cellulose. Bentonite ( colloidal hydrated aluminium silicate) Veegum (colloidal aluminium magnesium silicate. .THE END

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Foaming: If the density of the particle is less than the density of the liquid medium, the negative velocity of the particle results, this is the rate of floating or creaming. Remedy: Minor modification to the aqueous phase is necessary.

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Microbial growth: Most suspensions have almost neutral pH and susceptible for microbial growth. Remedy: Preservatives should be added.

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Change in particle size: Some times the particle size may be changed. Generally particle size is increased. Increased particle size helps in rapid settling. Remedy: By using viscosity imparting agents.

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