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Digitally signed by Fahad Hussain DN: cn=Fahad Hussain, o=PharmaMirror, ou, emai, c=BD Date: 2011.04.

29 09:32:01 +06'00' STABILITY PROBLEMS OF EMULSION EMULSION Emulsion may be defined as a biphasic sy stem consisting of two immiscible liquids usually water and oil, one of which is finely subdivided and uniformly dispersed as droplets throughout the other. Sin ce 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 accepta ble emulsion is known as its instability. The signs of instability are 1. Floccu lation or coagulation 2. Creaming 3. Coalescence 4. Breaking or cracking 5. Phas e inversion 6. Deterioration by micro-organism 7. Miscellaneous physical and che mical changes. Flocculation: Flocculation is the joining together of globules to form large clumps or floccules within the emulsion. In flocculation the interfa cial film and the individual droplets remain intact the globules do not coalesce and may be redispersed by shaking. Cause: Flocculation depends on the electrica l potential on the surface of the droplets. There is a high repulsive force amon g 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 emu lsifying 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 ens ure the presence of a high energy barrier and these reduce the incidence of floc culation. 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. w w w .P ha r m aM FACTORS AFFECTING THE STABILITY OF AN EMULSION Particle size: Increased particle size of the internal phase causes the decreased stability of an emulsion. Small er size of the particles of internal phase is always preferable. Particle-partic le interaction: Deflocculated particles are always preferable because the less t he particleparticle interaction the more the stability of an emulsion. Particle density: The less the particle density the more the stability of an emulsion. Bu lk phase/external phase density: the more the bulk phase density the more the st ability of an emulsion. Bulk phase viscosity: Generally the more the viscosity o f bulk phases the more the stability of emulsion. irr o r.c The phase which makes globules or droplets is known as internal phase or dispers e phase and other is external or continuous phase. Oil can be present as interna l and external phase and water also as internal or external phase. Emulsion is n ormally opaque. Particle sizes of emulsion are from 0.1 to 100 m. It can be used orally, topically and parentally. om

Cause: Creaming is influenced by gravity on the globules. So it depends on the s edimentation or creaming rate. This rate depends i. diameter of the dispersed gl obules ii. Viscosity of the dispersion medium iii. Density difference between tw o phases Creaming of emulsion can be explained by stokes law 2r2 (d1-d2)g D2 (d1 -d2)g V=-----------------------V=-----------------------18h 9h Where V= rate of crea ming r= particle radius in cm D =particle diameter in cm d1=density of the inter nal phase d2=density of the external phase g= gravitational constant h= viscosity of the external phase From the equation we can say i. Increase diameter of globu les increases the velocity and vice versa. ii. Increase viscosity of the dispers ion medium decreases the velocity and vice versa. iii. If d1>d2- downward creami ng d1<d2- upward creaming d1=d2- No creaming Remedy: i. Reduction of the globule s size by using an efficient homogenizer. ii. Increasing the viscosity of the co ntinuous phase by using viscosity imparting agent. iii. By reducing the density difference between two phases. iv. By controlling the dispersed phase concentrat ion. v. By storing in a cool place or low temperature. w w Coalescence: Coalescence is the fusing of the globules into larger drop or drops . In coalescence the globules lose their individuality. During fusion the interf acial film is destroyed. So coalescence is irreversible. Globules can not be red istributed by shaking. Cause: Coalescence depends on the structural properties o f the interfacial film. So it occurs when emulsifying agent loses its activity o r the amount of emulsifying is insufficient. Remedy: i. By adding sufficient amo unt of emulsifying agent and passing the product through the proper emulsifying machinery. ii. During preparation the addition of emulsifying agent should be ap propriate because the use of wrong emulsifying agent loses its activity within a short period of time. Breaking or Cracking: This involves coalescence of the di spersed globules and separation of the dispersed phase as a separate layer. Redi spersion can not be achieved by shaking and therefore the advantages of emulsifi cation are lost and accurate dosage form is impossible. Cause: Cracking may be c aused any physical or biological or chemical effect that changes the nature of t he interfacial film of an emulsifying agent. The physical factors causing breaki ng are described below. i. Opposite types of emulsifying agent: Addition of an e mulsifying agent of opposite type tends to decrease the power of emulsification which cause cracking. Example: Soaps of monovalent metals (Sodium lauryl sulphat e) produce o/w emulsion while soaps of divalent metals (Calcium lauryl sulphate) produce w/o emulsion. Addition of w .P ha r m aM irr o r.c om

ii. iii. iv. v. vi. Remedy: i. ii. iii. iv. monovalent soap to a divalent soap emulsion or a divalent soap to a monovalent s oap emulsion leads to instability or cracking. Addition of common solvent: Addit ion of a solvent in which both disperse and continuous phase are soluble forms a single phase system. Temperature: An increase in temperature may coagulate cert ain types of macromolecular emulsifier which are protein in nature cause instabi lity of an emulsion. An increase in temperature will increase the number of coll ision between globules that are effective in overcoming the barrier to coalescen ce and instability of an emulsion. Freezing: If an emulsion is kept below 40C th e 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: Emulsio n with a disperse phase concentration in excess of 74% has a marked tendency to crack. Addition of insufficient amount of emulsifying agent. By incorporating mo re emulsifying agent. By controlling the temperature at which emulsion is kept. By controlling disperse phase concentration. By adding correct emulsifying agent . w w Deterioration by micro-organism: Mold, yeast and bacteria may a. Bring about the decomposition of the emulsifier. b. Contaminate the aqueous phase. c. Destroy o il soluble vitamins. Remedy: Add chemical agent that will act specially as prese rvative. 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 preser vatives should be used one for oil phase and other for aqueous phase. The emulsi fying agent and other ingredients of the formulation should not form complex wit h the preservatives. Miscellaneous: Care must be taken to protect emulsion again st deterioration caused by light, temperature and freezing and thawing. STABILIT Y PROBLEMS OF SUSPENSION The ideal characteristics of a suspension are 1. The se dimentation is less as possible 2. The sediment is redispersible According to st rokes 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 densi ty difference between particle and medium Inversely proportional to the viscosit y of the medium. Mathematical expression 2r2 (d1-d2)g V=-----------------------9h D2 (d1-d2)g V=-----------------------18h w .P

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m aM irr o 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 degra dation. But there is some effect of physical factor i. By changing the phase vol ume ratio. ii. By cooling the emulsion specially those which are prepared by hea ting and mixing of two phases.

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Where, V= velocity of sedimentation in cm/sec r= particle radius in cm D= partic le diameter in cm d1=density of the particle in gm/cc d2=density of the medium i n gm/cc g= gravitational constant =980cm/sec2 h= viscosity of the medium. The char acteristics 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 diff erent for different suspension. Problems associated with suspension preparation 1. Caking and poor redispersibility 2. Cap locking 3. Color change 4. Crystal gr owth 5. Deflocculation 6. Decrease in drug potency 7. Change in flavor 8. PH cha nge 9. Change in viscosity 10. Rapid settling 11. Change in particle size 12. Mi crobial growth 13. Foaming 14. Chemical interaction 15. Dispersion of hydrophobi c drug w w Caking and poor redispersibility Caking is a compact mass of insoluble solids pa rticle formed generally in deflocculated suspension. Cause: Due to the smaller s ize of the particle, the rate of sedimentation of deflocculated suspension is ve ry 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 intera ction, the repulsive forces between particles are overcome and a hard cake is fo rmed which is difficult to redisperse. Remedy: a. By using flocculating agent: f locculating agents prevent cake formation by the flocculation of the particles. The process of flocculation as well as the stabilization of the suspension are m entioned below: The particles, irrespective of their charge are coated with posi tively charged agent. The particles are flocculated by the use of a negatively c harged agent to bring the product in to the non caking zone. Finally a minimum a mount of the desired suspending agent or mixture of suspending agents is added a nd the suspension is again observed for optimum flocculation and freedom from ca king. Examples of flocculating agents: Electrolytes, Surfactants, polymers b. By using viscosity imparting agent: w .P ha r m aM irr o r.c om

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 c ake formation. So we can prevent the cake formation using viscosity imparting ag ents. Examples : Acacia, Tragacanth, Agar c. Caking is prevented by controlling of pH of the dispersion phase. d. It can be controlled by decreasing particle si ze. Cap Locking Cause Caplocking is a filling problem which occurs when the disp ersed particles crystallize on the threads of the bottle cap and interface in ca p removal. Remedy Caplocking can be prevented by using different vehicle contain ing sucrose, glucose, sorbital and glycerine. Color change: Cause: Light sensiti ve color may be changed in presence of light. Due to the increased in surface ar ea some color may be changed. Remedy: By keeping the bottle in dark place. Deflocculation: Cause: w w Remedy: By using flocculating agent Electrolytes Detergents Polymer Decrease in drug potency: Cause: Change in flavor: Cause: w .P ha r 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: m Crystal growth: Cause: There is always a degree of crystal growth which mainly o ccurs in storage condition due to Temperature fluctuation pH change Impurity Low solubility aM irr o r.c om

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 s tability also ensure physiological compatibility. Change in viscosity: The visco sity of the suspension may be changed on long term use. Remedy: By using suffici ent viscosity imparting agents. Rapid settling: Some times rapid settling of par ticles is found in suspension. Remedy: By decreasing the particle size. By using viscosity imparting agents. w w Chemical interaction: Chemical interaction may be arisen during the addition of additives to the drug such as cationic surfactants react with any anionic ingred ients. Remedy: Care should be taken when additive added to the drug. Dispersion of hydrophobic drugs: Hydrophobic drug particles do not dissolve in water. So su spension of hydrophobic drug creates some problem in particle dispersion. Remedy : Wetting agents are used in this concern which promotes the dispersion of hydro phobic drug in water. Examples of wetting agents: Surfactants Sodium carboxy met hyl cellulose. Bentonite ( colloidal hydrated aluminium silicate) Veegum (colloi dal aluminium magnesium silicate. .THE END w .P Foaming: If the density of the particle is less than the density of the liquid m edium, the negative velocity of the particle results, this is the rate of floati ng or creaming. Remedy: Minor modification to the aqueous phase is necessary. ha r m Microbial growth: Most suspensions have almost neutral pH and susceptible for mi crobial growth. Remedy: Preservatives should be added. aM Change in particle size: Some times the particle size may be changed. Generally particle size is increased. Increased particle size helps in rapid settling. Rem edy: By using viscosity imparting agents. irr o r.c om