emulsion

dispersed system emulsion dosage form

1. EMULSION Mr.R.R.Patil Dr.Shivajirao Kadam College of Pharmacy, Kasbe digraj, Sangli

2. INTRODUCTION An emulsion is a dispersion in which the dispersed phase is composed of small globules of a liquid distributed throughout a vehicle in which it is immiscible. Vigorous shaking may break one liquid into globules that become distributed throughout the other, this condition is only temporary as separation quickly take place on standing. e.g castor oil and water

3. Classification of emulsions Based on dispersed phase Oil in Water (O/W): Oil droplets dispersed in water Water in Oil (W/O): Water droplets dispersed in oil Based on size of liquid droplets 0.2 –50 mm Macroemulsions (Kinetically Stable) 0.01 –0.2 mm Microemulsions (Thermodynamically stable)

4. Emulsifying Agent Emulsifying agent are the third substance or agent which produce the film at the interface between two immiscible liquids and stabilised the system those agent are called emulsifying agent or emulsifier or emulgent. Pharmaceutically acceptable emulsifiers must also be stable be compatible with other ingredients be non –toxic possess little odor , taste , or color not interfere with the stability of efficacy of the active agent

5. Emulsion dosage form present in liquid or semi-solid form. Liquid emulsions are used internally, externally or parenterally. The o/w type of emulsions orally used bec. they disguise the taste or oiliness of medicinal oils such as paraffin, cod liver oil & also improve absorption of oils. for some patients, o/w type of nutritive oils & fats are administered intravenously. For both liquid & semi-solid external preparations o/w are superior to w/o emulsions. w/o type of emulsion used on non-weeping surface or dry surface to prevent dehydration (emollient).

6. Theory of Emulsification INTERFACIAL TENSION : Interfacial or surface tension exists when two phases are present. These phases can be gas/oil, oil/water, or gas/water. Interfacial tension is the force that holds the surface of a particular phase together and is normally measured in dynes/cm . INTERFACIAL FILM: In interfacial film , an amphiphilic molecules to align it self at water-oil interface in the favorable position such as, - Oleophilic portion in oil phase. & - Hydrophilich portion in water phase.

7. e.g. O/W OLEOPHILIC PART HYDROPHILIC PART

8. For the amphiphilic to be concentrated at the interface, it must be balanced with the proper amount of water- and oil-soluble groups. If the concentration of the emulsifier is high enough, it forms a rigid film between the immiscible phases, which acts as a mechanical bar to both adhesion & coalescence of the emulsion.

9. Determination of Emulsion Type Dilution Test: - o/w emulsion can be diluted with water. - w/o emulsion can be diluted with oil. Conductivity Test: - Electrodes are used in that test. - In o/w type emulsion the lamp will light. - In w/o type emulsion the lamp fails to light.

10. Dye-Solubility Test: - water soluble dye will dissolve in the aqueous phase. - oil soluble dye will dissolve in the oil phase. CoCl 2 / Filter paper Test: Filter paper impregnated with CoCl 2 dried (blue) changes to pink when o/w emulsion is added. This test may fail if emulsion is unstable or break in the presence of electrolytes.

11. Classification of Emulsifying Agents Natural emulsifying agents from vegetable sources Acacia Tragacanth Agar Pectin Starch

12. 2. Natural emulsifying agents from animal sources Gelatin Egg yolk Wool fat 3. Semi-synthetic polysaccharides Methyl cellulose Sodium carboxymethyl cellulose. 4. Synthetic emulsifying agents Anionic Cationic Non-ionic

13. 5. Inorganic emulsifying agents Milk of magnesia Magnesium oxide Magnesium trisilicate Bentonite 6. Saponins 7. Alcohols Cholesterol Carbowaxes Lecithin

14. Natural emulsifying agents from vegetable sources Acacia:- Acacia is the best emulsifying agent for extemporaneous preparation of emulsions for internal use. They are stable over a wide range of pH 2 to 10. These emulsions usually have low viscosity therefore creaming take place which can be prevented by increasing viscosity of the medium by incorporating tragacanth , agar or pectin along with acacia.

15. Tragacanth:- It is rarely used as an emulsifying agent. It produces very coarse & thick emulsions & sometimes viscosity increases to much an extent that pouring of the emulsion becomes problem. It is used mainly as an emulsion stabiliser, particularly in acacia emulsions. A suitable proportion is 1 part to 10 parts of acacia.

16. Pectin:- Pectin is carbohydrate obtained from inner part rind of citrus fruit & from the apple pulp & guava. It acts as a emulsion stabilizer in acacia emulsions. If it is used as emulsifying agent a ratio of 0.1 gm per gram of acacia. A mucilage of pectin is first prepared before adding it to the preparation. To prevent clumping with water it should previously wetted with alcohol, glycerol or syrup.

17. AGAR:- Agar is a dried extract from certain seaweeds. It is not a good emulsifying agent as it forms a very coarse & viscous emulsion. It was formerly used as an emulsion stabiliser in liquid paraffin emulsions prepared with acacia. Generally 2% mucilage of agar is prepared by dissolving it in boiling water & cooled to 45 C. below this it forms a gel which is not useful in emulsion.

18. Natural emulsifying agents from animal sources Gelatin:- - Gelatin is mainly used for the emulsification of liquid paraffin. 1% concentration forms the emulsion. Gelatin emulsions are prone to bacterial growth therefore suitable preservative must be incorporated.

19. Egg yolk:- Egg yolk itself is an emulsion bec. It contains lecithin & cholesterol which acts as emulsifying agent. It is generally used for the emulsification of fish liver oils. 15grms egg yolk obtained from each egg which can emulsify about 120 ml of fixed oil & 60 ml volatile oil. Preservatives must be used in that type of emulsion.

20. Wool Fat:- Wool fat also called as anhydrous lanolin It is type of wax. It’s M.P is 36 to 40 C. It consist of fatty acid esters of cholesterol & fatty alcohols. It is poorly absorbed in skin but with soft paraffin or vegetable oils produce creams that penetrate well & assist absorption of medicaments. It is used in W/O type of emulsion. It absorbed 50% of water but it mixed with other fatty substances it can emulsify several times its own weight of water & other hydroalcholic liquids.

21. Semi-synthetic polysaccharides: Methyl Cellulose:- It is available methyl cellulose 20, methyl cellulose 2500 & 4500 the numbers indicate their viscosity in aq.solution. It is used emulsification of mineral oil & vegetable oil but less satisfactory for cod liver oil. It is soluble in hot water. It is stable to pH changes & alcohol but produces ppt in the presence of large amounts of electrolytes.

22. Sodium Carboxymethyl Cellulose:- It is not used as true emulsifier . It is used as an emulsion stabilizer in the concentration of 0.5 to 1.0%. It is soluble in cold water & hot water.

23. Synthetic Emulsifing Agents or Surfactants : Anionic:- It is used good emulsifing agents for those emulsions which are applicable for external purpose. various alkali soaps, metallic soaps, sulphated alcohols & sulphonates are used as emulsifing agents. It produce O/W type of emulsion. Sulphated salts, sodium lauryl sulphate is commonly used as emulsifing agent in topical preparation Dioctyl sodium sulphsuccinate is e.g. of sulphonates used internally for soften the stools.

24. Cationic:- They are used emulsifing agent in O/W type of emulsions. Quaternary ammonium compounds are only group that extensively used emulsifing agent. They have show against bacterial properties, so it is used for disinfectant. It is not good emulgent when it singly but with alkali sulphates & phosphates it produce good emulsions. When combined with fatty alcohols it shows greater stability. It is stable at pH range 3 to 7.

25. Non-Ionic:- Non-ionic surfactant are widely used in the pharmaceutical emulsion. Those emulsions are stable over a wide range of pH. It’s not affected by addition of acids & electrolytes. The most commonly used surfactant are glyceryl monostearate, polyoxyethylene glycol esters & ethers & sorbitan monopalmitate.

26. Inorganic Emulsifying Agents:- Various inorganic emulsifying agents are used such as milk of magnesia, magnesium oxide, bentonite etc. They produce O/W type of emulsions. But bentonite used either O/W or W/O type of emulsion. 5% suspension of bentonite is used as a emulsifying agent. For O/W oil is added to the bentonite suspension. For W/O oil is placed in the container & then bentonite suspension added to the oil & rapid stirring.

27. SAPONINS Saponins are rarely used as emulsifying agents. Quillaia tincture or panama tincture & liquid extract may be used.

28. ALCOHOLS Cholesterol:- A number of high molecular weight alcohols are used. They used as a stabiliser in emulsion preparation. Cetyl alcohol, stearyl alcohol, glyceryl monostearate included in this group.

29. Carbowaxes:- They act as non-ionic emulsifying agents. They are used in the ointments & cream preparations. Their M.W various from 200-1000 Carbowaxes 200-700 are viscous & light coloured. Carbowaxes M.W 1000 are wax like solid.

30. Lecithins:- Lecithin forms W/O type emulsion. It is rarely used as emulsifying agent. Because it exposed to light & gets easily oxidised.

31. Hydrophile-Lipophile Balance (HLB) Discovered by griffin scientist in 1954. This system is useful of classification on non-ionic surfactants related to their behavior & solubility in aqueous system or water. The numerical values, called the Hydrophile-Lipophile Balance (HLB), denote the relative affinity for oil & water. Oil soluble materials have low value & water soluble materials have high values.

32. On HLB assigns various numbers which vary from 1-20. Numbers are calculated from saponification values (esters) and acid value number (fatty acid). Emulsifying agent with high HLB values i.e. 7 to 20 produce O/W emulsions (hydrophilic) & those with low HLB values i.e. 3 to 6 produce W/O emulsion (lipophilic).

33. Sr.No. Name of Emulsifying Agent HLB Value Type of Emulsion 1. Acacia 8.0 O/W 2. Tragacanth 13.2 O/W 3. Glyceryl monostearate 3.8 W/O 4. Sorbitan mono- stearate 4.7 W/O 5. Sorbitan monooleate 4.3 W/O

34. Preparation of Emulsion Dry gum method Bottle Method Wet gum method Step involved to form Primary Emulsion -In dry gum method the oil is first triturated with gum & then water is added. - In wet gum method the first gum triturated with water to form a mucilage & then oil added in small quantities.

35. Table shows Proportions of oil, water & Gum acacia Proportion of Oil : Water: Gum Fixed Oils 4 : 2 : 1 Volatile Oils 4 : 4 : 2 Fixed Oils:- Castor oil, Cod liver oil, Shark liver oil, Olive oil, Almond oil, Liquid paraffin. Volatile Oils:- Turpentine oil, Sandal wood oil, Cinnamon oil, Peppermint oil

36. Dry Gum Method / Continental Method “4:2:1" Method 4 parts (volumes) of oils 2 parts of water 1 part of gum In dry gum method the oil is first triturated with gum & then water is added.

37. Wet Gum Method / English Method 4 parts (volumes) of oil 2 parts of water 1 part of gum In wet gum method the first gum triturated with water to form a mucilage & then oil added in small quantities.

38. Bottle Method/ Forbes Bottle Method This method useful for the volatile & other non-viscous oils. Because of low viscosity the volatile oils it requires greater amount of gum. This method also called 4 : 4: 2 method. Oil is put in large bottle + Gum (shaken until mixed) + Water (to form primary emulsion) then volume make up with water.

39. Other Method HOMOGENISER

40. Hand Homogeniser

41. MICROEMULSIONS Defined as dispersion of insoluble liquids in a second liquid that appear clear & homogeneous to the naked eye. Microemulsions are also called Transparent emulsion Solubilized system Micellar solution

42. Microemulsions should not be confused, however, with solutions formed by co- solvency. e.g. the clear system consisting of water, benzene, and ethanol. It can be prepared with emulsifying agents which give a local negative interfacial tension & forms monomolecular interfacial films.

43. INSTABILITY OF EMULSION Cracking In cracking, separation of the disperse phase & continuous phase. Cracking may be caused by any chem., physical or biological effect that changes the nature of emulsifying agent or tends to make it less stable.

44. Causes of Cracking Addition of opposite type of emulsifying agent: Monovalent soap metals produce O/W type of emulsion & divalent soap metals produce W/O type of emulsion. - If monovalent soap added in divalent soap of emulsion or divalent soap added in monovalent it causes cracking of emulsion.

45. Precipitation or Decomposition of Emulsifying agent: Gums, Gelatin & casein are insoluble in alcohol if this solvent is transferred to prepared emulsion, that time the emulgent precipitate & cracking was caused. Anion emulgent are incompatible with large cations & cation emulgent are incompatible with large anions.

46. By addition of Common Solvent: If common solvent was added in prepared emulsion that time cracking was showed. E.g. alcohol is added in turpentine oil liniment, alcohol is soluble with turpentine oil, soft soap & water are soluble in alcohol that time destroying the emulsion.

47. Creaming E.g. Milk Creaming may be defined as the formation of a layer of relatively concentrated emulsion. Creamed emulsion may be made homogeneous again by shaking, creaming is less serious type of instability than cracking. Creaming is undesirable bec. The closeness of the globules in the cream favours breakdown of the interface.

48. Following are ways in which creaming may be minimised: Reducing the mean size & the size distribution of the globule s:- The size of the globules made either by hand or mechanical mixer, the globule range from 1 to 50 µm, but effectively homogenisation will reduced their diameter to form 1 to 3 µm. Increasing the viscosity of the continuous phase :- - syrup & glycerin used, they changes in density betw.continuous & dispersed phase & those are unsuitable. - Tragacanth, sodium alginate & methylcellulose are increases viscosity, without affecting density, useful for O/W & soft paraffin is useful for W/O emulsion. Storage in cool place :- - Temp. rise affect on viscosity. & freezing of the aqua. phase must be avoided , ice may separate & exerting pressure on the globules, causes cracking.

49. Phase Inversion It is Physical Instability In that changes phase O/W to W/O & vice versa. it causes, addition of electrolytes or changing phase ratio or by temperature. It can be minimised by, proper emulsifying agent in adequate conc. & conc. of dispersed phase betw. 30 to 60 percent.

50. Phase Inversion Temperature formulation (PIT/HLB temperature ) The temperature at which the inversion occurs depends upon emulsifier concentration is called as PIT. e.g. it was observed that water in benzene W/O were stabilized with sodium stearate convert to O/W upon heating & reform W/O emulsion upon cooling. Since in that formation those emulsion are prepared at relatively high temperature & then cool at room temperature.

51. Coalescence Coalescence is a growth process during which the emulsified particles join to form large particle. Particularly occurs in O/W systems containing nonionic surfactants & in W/O system in which electrical effect are negligible. So that reason, variety of natural gums & proteins used at low levels & can be used at higher concentration as primary emulsion.

52. PACKAGING Depending on the use, emulsions should be packed in suitable containers. Emulsions meant for oral use are usually packed in well filled bottles having an air tight closure. Light sensitive products are packed in amber coloured bottles. For viscous emulsions, wide mouth bottles should be used. The label on the emulsion should mention that these products have to be shaken thoroughly before use. External use products should clearly mention on their label that they are meant for external use only. Emulsions should be stored in a cool place but refrigeration should be avoided as this low temperature can adversely effect the stability of preparation.

53. EVALUATION TESTS Determination of particle size and particle count: It is performed by optical microscopy, sedimentation by using Andreasen apparatus and Coulter counter apparatus.  

54. Determination of viscosity: For viscous emulsions, the use of penetrometer instrument is used.

55. Determination of phase separation: This is another parameter used for assessing the stability of the formulation. Phase separation may be observed visually or by measuring the volume of the separated phases. Determination of electrophoretic properties:- Determination of electrophoretic properties like zeta potential is useful for assessing flocculation since electrical charges on particles influence the rate of flocculation. O/W emulsion having a fine particle size will exhibit low resistance but if the particle size increase, then it indicates a sign of oil droplet aggregation and instability.

56. STABILITY The stress conditions used for speeding up instability of emulsions include: Centrifugal force, Agitation force Aging and temperature  Centrifugation: In that centrifugation at 3750 rpm in a 10 cm radius centrifuge for a period of 5 hours is equivalent to the effect of gravity for about 1 year.

57. Agitation:- In that method observing the Brownian movement of droplets. It is believed that no coalescence of droplet take place unless droplets impinge upon each other.