1. EMULSIONs DEPARTMENT OF PHARMACEUTICS Lam,guntur
CHALAPATHI INSTITUTE OF PHARMACEUTICAL SCIENCES
Lam,guntur

2. Outline Definition Classification Identification of emulsion
Application of emulsion
Theory of emulsification
Formulation of emulsion
Emulsification techniques
Reference

3. What is an emulsion
An emulsion is a thermodynamically unstable system consisting of at least two immiscible liquid phases one of which is dispersed as globules in the other liquid phase stabilized by a third substance called emulsifying agent.
dispersed phase
continuous phase

4. Pharmaceutical applications of emulsions:
They can mask the bitter taste and odor of drugs, e.g. castor oil, cod-liver oil etc.
They can be used to prolong the release of the drug thereby providing sustained release action.
Essential nutrients like carbohydrates, fats and vitamins can all be emulsified and can be administered to bed ridden patients as sterile intravenous emulsions.
Emulsions provide protection to drugs which are susceptible to oxidation or hydrolysis.
Intravenous emulsions of contrast media have been developed to assist in diagnosis.
Emulsions are used widely to formulate externally used products like lotions, creams, liniments etc.

5. Classification of emulsions
1. Based on dispersed phase
- Simple emulsions
Oil in Water (O/W)
Water in Oil (W/O)
- Multiple emulsions
Oil-in-water-in-oil (O/W/O)
Water-in-oil-in-water (W/O/W)
- Micro emulsions
(Globule size is less than 120 nm, they appear to be transparent.)
2. Based on size of liquid droplets
0.2 – 50 mm Macro emulsions (Kinetically Stable)
0.01 – 0.2 mm Micro emulsions (Thermodynamically Stable)
Classification of emulsions

6. SIMPLE EMULSION

7. DIFFERENCE BETWEEN O/W AND W/O EMULSIONS
Water in oil emulsion (w/o)
Oil in water emulsion (o/w)
Oil is the dispersion medium and water is the dispersed phase
Water is the dispersion medium and oil is the dispersed phase
They are greasy and not water washable
They are non greasy and easily removable from the skin surface
They are used externally to prevent evaporation of moisture from the surface of skin e.g. Cold cream
They are used externally to provide cooling effect e.g. vanishing cream
Oil soluble drugs are more quickly released from w/o emulsions
Water soluble drugs are more quickly released from o/w emulsions
They are preferred for formulations meant for external use like creams.
They are preferred for formulations meant for internal use as bitter taste of oils can be masked.
W/O emulsions go not give a positive conductivity test as oil is the external phase which is a poor conductor of electricity.
O/W emulsions give a positive conductivity test as water is the external phase which is a good conductor of electricity.

8. Multiple emulsion Also called emulsion within emulsion
They are developed with a view to delay the release of an active ingredient. They have three phases.
They may be oil-in-water-in-oil (o/w/o) or of water-in-oil-in-water (w/o/w).
W/O/W SYSTEM
O/W/O SYSTEM
water phase oil phase

9. PREPARATION OF MULTIPLE EMULSIONS (TWO STEP METHOD)

10. MICROEMULSION
They may be defined as dispersions of insoluble liquids in a second liquid that appears clear and homogenous to the naked eye.
They are frequently called solubilised systems because on a macroscopic basis they seem to behave as true solutions.
As in micro emulsions the globule size is less than 120 nm,
they appear to be transparent.
Example:
Etoposide micro emulsion
methotraxate micro emulsion

11. Microemulsions
Microemulsions are thermodynamically stable optically transparent , mixtures of a biphasic oil –water system stabilized with surfactants.
Micro emulsion
Emulsion
Transparent
Yes No
Size nm
0.1 – 10 µ
Formation
Spontaneous
Require vigorous shaking
Type
o/w, w/o. cylinder
o/w, w/o, w/o/w, o/w/o
Stability
Thermodynamically stable
Thermodynamically unstable
Viscosity
Can accommodate 20 to 40% without increase in viscosity
More viscous

12. Micro emulsion/macro emulsion
Thermodynamically stable
Droplet size is nm (transparent)
High surface area (200m2/g)
Kinetically stable
1-10 microns (opaque)
Low surface area (15m2/g)

13. Pharmaceutical applications of microemulsions
Increase bioavailability of drugs poorly soluble in water.
Topical drug delivery systems
Oral products
It covers the unpleasant taste
Increases absorption rate
O/W Parenteral use emulsion
i/v lipid nutrients
i/m – depot effect for water soluble antigenic material
Topical use :
Washable
Acceptable viscosity
Less greasy

14. To mask the taste
O/W is convenient means of orally administration of water- insoluble liquids
O/W emulsion facilitates the absorption of water-insoluble compounds comparing to their oily solution preparations (e.g. vitamins)
Oil-soluble drugs can be given parentrally in form of oil-in water emulsion. (e.g. Taxol)
Emulsion can be used for external application in cosmetic and therapeutic uses.

15. Identification of emulsion
DILUTION TEST:
In this test the emulsion is diluted either with oil or water. If the emulsion is o/w type and it is diluted with water, it will remain stable as water is the dispersion medium" but if it is diluted with oil, the emulsion will break as oil and water are not miscible with each other.
Add drops of water
Add drops of water
Water distribute
Uniformly
O/W Emulsion
W/O Emulsion

16. CONDUCTIVITY TEST water is good conductor of electricity whereas
oil is non-conductor. Therefore, continuous phase of water runs
electricity more than continuous phase of oil.
Emulsion
Emulsion
Bulb glows with O/W
Bulb doesn’t glow with W/O

17. DYE TEST Dye Solubility test:
Water soluble dye (methylene blue) will be taken up by the aqueous phase where as oil soluble dye will be taken by oily phase.
When microscopically it is observed that water soluble dye is taken up by the continuous phase ,it is o/w emulsion.
If the dye is not taken up by the continuous phase , test is repeated with oil soluble dye.. Coloring of continuous phase confirms w/o emulsion. This test can fail if ionic emulsions are present.

18. Water Soluble Dye Ex. Amaranth Dye
water is continuous phase
Oil is dispersed phase
O/W EMULSION
oil is continuous phase
water is dispersed phase
W/O EMULSION
Water-soluble dye will dissolve in the aqueous phase.

19. Oil Soluble Dye Ex. scarlet
water is continuous phase
Oil is dispersed phase
O/W EMULSION
oil is continuous phase
water is dispersed phase
W/O EMULSION
Oil-soluble dye will dissolve in the oil phase.

20. Fluorescent test
Oils give fluorescence under UV light, while water doesn’t. Therefore, O/W emulsion shows spotty pattern while W/O emulsion fluoresces.
When a w/o emulsion is exposed to fluorescent light under a microscope the entire field fluorescence. If the fluorescence is spotty, then the emulsion is of o/w-type.
However, all oils do not exhibit fluorescence under UV light and thus the method does not have universal application.

21. COCL2/ FILTER PAPER TEST
Filter paper impregnated with CoCl2 and dried appear to be blue but when dipped in o/w emulsion changes to pink.
This test may fail if emulsion unstable or breaks in presence of electrolyte

22. CREAMING TEST
The direction of creaming identifies the emulsion type, if the densities of aqueous and oil phases are known.
Water-in-oil emulsions normally cream downward as oil is usually less dense than water.
Oil-in-water emulsions normally cream upwards.

23. APPLICATIONS OF EMULSIONS
For prolonged action
Taste masking
Improved stability
Parenteral preparation
Enzyme entrapment
Increased Oral bioavailability

24. instability of emulsion
Emulsification is not a spontaneous process and hence emulsions have minimal stability.
Reasons for instability can be understood from the nature of immiscible phases and their interfacial properties.
When two immiscible liquids are agitated together
polar (aqueous) and non polar (oil) liquids are mixed together
one of the liquids forms small droplets and gets dispersed in the other liquid
forms an emulsion.

25. When left aside, droplets fuse themselves and finally separate as two layers. This in an indication of instability of an emulsion.
Except in the case of very dilute oil-in-water emulsions (oil hydrosols), which are somewhat stable, the liquids separate rapidly into two clearly defined layers.
The state of instability may be described by the fact that the cohesive force between the molecules of each separate liquid is greater than the adhesive force between the two liquids.
Any attempt to increase the adhesive forces between these phases can produce a stable emulsion.
A system is said to be thermodynamically stable, if it possesses low surface free energy.
The higher the interfacial area, the greater is the interfacial free energy, and hence lower the stability.

26. instability of emulsions
Flocculation and creaming
Coalescence and breaking
(c) Miscellaneous physical and chemical changes
(d) Phase inversion.

27. Flocculation
Neighboring globules come closer to each other and form colonies in the continuous phase. This aggregation of globules is not clearly visible.
This is the initial stage that leads to instability.
Flocculation of the dispersed phase may take place before, during or after creaming.

28. The extent of flocculation of globules depends on
(a) globule size distribution.
(b) charge on the globule surface.
(c) viscosity of the external medium.
(a) Globule size distribution
Uniform sized globules prevent flocculation.
This can be achieved by proper size reduction process.
(b) Charge on the globule surface
A charge on the globules exert repulsive forces with the neighboring globules.
This can be achieved by using ionic emulsifying agent, electrolytes etc.

29. (c) Viscosity of the external medium.
If the viscosity of the external medium is increased, the globules become relatively immobile and flocculation can be prevented.
This can be obtained by adding viscosity improving agents (thickening agents) such as hydrocolloids or waxes.
Floccules slowly move either upward or downward leading to creaming.
Flocculation is due to the interaction of attractive and repulsive forces, whereas creaming is due to density differences in the two phases.

30. It can be observed by a difference in color shade of the layers.
Creaming
Creaming is the concentration of globules at the top or bottom of the emulsion.
Droplets larger than 1 mm may settle preferentially to the top or the bottom under gravitational forces.
Creaming may also be observed on account of the difference of individual globules (movement rather than flocs).
It can be observed by a difference in color shade of the layers.

31. It is a reversible process, i. e
It is a reversible process, i.e., cream can be redispersed easily by agitation, this is possible because the oil globules are still surrounded by the protective sheath of the emulsifier.
Creaming results in a lack of uniformity of drug distribution. This leads to variable dosage. Therefore, the emulsion should be shaken thoroughly before use.
Creaming is of two types, upward creaming and downward creaming

32. Upward creaming, is due to the dispersed phase is less dense than the continuous phase. This is normally observed in o/w emulsions. The velocity of sedimentation becomes negative.
Downward creaming occurs if the dispersed phase is heavier than the continuous phase. Due to gravitational pull, the globules settle down. This is normally observed in w/o emulsions.
Since creaming involves the movement of globules in an emulsion, Stokes’ law can be applied. ν = d2 (ρs – ρ0)
18 η0
ν = terminal velocity in cm/sec,
d is the diameter of the particle in cm,
ρs and ρ0 are the densities of the dispersed phase and dispersion medium respectively,
g is the acceleration due to gravity and
η0 is the viscosity of the dispersion medium in poise.

33. Creaming is influenced by,
Globule size
Viscosity of the dispersion medium
Difference in the densities of dispersed phase and dispersion medium.
Creaming can be reduced or prevented by:
1. Reducing the particle size by homogenization. Doubling the diameter of oil globules increases the creaming rate by a factor of four.
2. Increasing the viscosity of the external phase by adding the thickening agents such as methyl cellulose tragacanth or sodium alginate.
3. Reducing the difference in the densities between the dispersed phase and dispersion medium.
4. Adjusting the continuous phase and dispersed phase densities to the same value should eliminate the tendency to cream.
5. To make densities equal, oil soluble substances such as bromoform, β-bromo naphthalene are added to the oil phase (rarely used technique).

34. COALESCENCE
If the sizes of globules are not uniform, globules of smaller size occupy the spaces between the larger globules. A few globules tend to fuse with each other and form bigger globules.
This type of closed packing induces greater cohesion which leads to coalescence.
In this process, the emulsifier film around the globules is destroyed to a certain extent. This step can be recognized by increased globule size and reduced number of globules.

35. Coalescence is observed due to:
Insufficient amount of the emulsifying agent.
Altered partitioning of the emulsifying agent.
Incompatibilities between emulsifying agents.
Phase volume ratio of an emulsion has a secondary influence on the stability of the product and represents the relative volume of water to oil in emulsion.
At higher ratio (>74% of oil to water), globules are closely packed, wherein small globules occupy the void spaces between bigger globules.
Thus globules get compressed and become irregular in shape, which leads to fusion of adjacent globules.
Ostwald and others have shown that if one attempts to incorporate more than about 74% of oil in an o/w emulsion, the oil globules often coalesce and the emulsion breaks.
This value known as the critical point, is defined as the concentration of the dispersed phase above which the emulsifying agent cannot produce a stable emulsion of the desired type.

36. BREAKING
Separation of the internal phase from the external phase is called breaking of the emulsion.
This is indicated by complete separation of oil and aqueous phases, is an irreversible process, i.e., simple mixing fails. It is to resuspend the globules into an uniform emulsion.
In breaking, the protective sheath around the globules is completely destroyed and oil tends to coalesce.

37. PHASE INVERSION
This involves the change of emulsion type from o/w to w/o or vice versa.
When we intend to prepare one type of emulsion say o/w, and if the final emulsion turns out to be w/o, it can be termed as a sign of instability.

38. FORMULATION OF EMULSION
Aqueous phase: purified water
Organic phase: arachis oil, cod liver oil, sesame oil, castor oil
Emulsifier: acacia,SLS,tween,bentonite
Antioxidant: sodium bisulphite,sodium nitrite
Preservatives: methyl and propyl paraben

39. Emulsifying agents
Emulsifier or surface active agent (SAA) is molecule which has two parts, one is hydrophilic and the other is hydrophobic. Upon the addition of SAA, it tends to form monolayer film at the oil/water interface.
Mechanism of action of emulsifying agents:
When two immiscible liquids are agitated together so that one of the liquids is dispersed as small droplets in the other.
To prevent coalescence between globules, it is necessary to use emulsifying agent.

40. CLASSIFICATION OF EMULSIFYING AGENTS
Natural emulsifying agents from vegetable sources
Natural emulsifying agents from animal sources
Synthetic emulsifying agents
Finally divided emulsifying agents
Auxiliary divided emulsifying agents.
Saponins
Alcohols

41. Properties of an ideal emulsifying agent
Reduce the interfacial tension between the two immiscible liquids.
Physically and chemically stable, inert and compatible with the other ingredients of the formulation.
Completely non irritant and non toxic in the concentrations used.
Organoleptically inert i.e. should not impart any colour, odour or taste to the preparation.
Form a coherent film around the globules of the dispersed phase and should prevent the coalescence of the droplets of the dispersed phase.
Produce and maintain the required viscosity of the preparation.

42. A) NATURAL EMULSIFYING AGENTS FROM VEGETABLE SOURCES
Obtained from vegetable source
Anionic in nature
Produce O/W emulsions
Capable of emulsifying a large number of substances
Example:
Acacia
Tragacanth
Agar
Chondrus
Pectin
starch

43. ACACIA Emulsions formed are O/W. Stable over wide range of PH.
Soluble in water
Low viscosity that’s why creaming takes place
Should be preserved properly

44. TRAGACANTH
It alone is rarely used as an emulsifying agent because it doesn't reduce interfacial tension.
Produces very coarse and thick emulsion with increase viscosity.
Stable emulsion is produce when use along with acacia.

45. AGAR
Good emulsifying agents because they forms a very coarse and viscous emulsion
Used as thickening agent along with acacia.

46. CHONDRUS Like agar it is not used as primary emulsifier.
It is used as a thickening agent.
Used along with acacia for the emulsification of cod-liver oil.

47. PECTIN
It is a purified complex carbohydrate obtain from rind of citrus fruit.
It act as a emulsion stabilizer in acacia emulsions.
Mucilage of pectin is prepared before adding it to emulsion.
To prevent lump formation pectin is triturated with small amount of alcohol or glycerol.

48. B) NATURAL EMULSIFYING AGENTS FROM ANIMAL SOURCES
Obtained from animals body.
Examples :
Gelatin,
Egg yolk,
Wool fat.

49. GELATIN Mainly used for the emulsification of liquid paraffin.
Protein in nature
It possesses isoelectronic point.
Prone to bacterial growth
Suitable preservative should be added.

50. EGG YOLK
It itself is an emulsion because of the presence of lecithin and cholesterol
Rarely used in industrial preparations because it is spoiled during transportation.
Used in extemporaneous preparations.

51. WOOL FAT Also known as Anhydrous Lanolin
It is generally used in emulsion meant for external application.
It produces water in oil emulsions
It can absorb 50% of water

52. C) SEMI SYNTHETIC POLYSACCHARIDES
Methyl cellulose
Sodium carboxy methyl cellulose

53. METHYL CELLULOSE Synthetic derivative of cellulose
Used as suspending, thickening and emulsifying agent.
Commonly used for emulsification of mineral and vegetable oil.
Soluble in hot water therefore mucilage can be prepared easily.
Emulsions prepared are very stable.

54. SODIUM CARBOXY METHYL CELLULOSE
Not a true emulsifier
Used as an emulsion stabilizer.
Soluble in cold as well as hot water.

55. D) SYNTHETIC EMULSIFYING AGENTS
Group includes surface active agents used as emulsifying agents.
Classified by the ionic charges they posses.
Anionic, Cationic, Non-ionic

56. E)INORGANIC EMULSIFYING AGENTS
Inorganic substances like milk of magnesia, magnesium oxide are used in pharmaceutical emulsions.
Produce O/W emulsion

57. F) ALCOHOLS
Examples are cholesterol, carbowaxes, lecithin

58. LACITHIN Phospholipids in nature.
Obtained from nerve cells and Soya beans.
Show surface activity.
Highly stable and used for making W/O emulsions.
Chemicals used to overcome bad smell.

59. CHOLESTEROL Used to prepare W/O emulsions
Ability to absorb water is low.

60. G) SAPONINS Rarely used as emulsifying agents.
Quillaia tincture and liquid extracts may be used.

61. FINELY DIVIDED EMULSIFYING AGENTS
Having suitable hydrophilic and lipophilic properties.
If wetted with oil W/O emulsions are formed.
If wetted with water O/W emulsions are formed.
Clay, Pt, Ag in finally divided form is used as emulsifying agent.

62. AUXILLARY EMULSIFYING AGENTS
Normally incapable of forming stable emulsion but main function is thickening agent.
Agar and stearic acid.

63. Methods of emulsion preparation
On small scale:
Porcelain mortar and pestle
On large scale:
Mechanical stirrer
Proportions of primary emulsion
Type of oil
oil
water
gum
Fixed oil 4 2 1
Mineral oil 3
Volatile oil

64. Flow chart for emulsion preparation
Disperse
phase
Continuous
phase
PRE – MIX OR
CRUDE DISPERSION
OTHER ADDITIVES
(FLAVOURS,
COLOURING AGENT)
pH ADJUSTMENT
VOLUME ADJUSTMENT
HOMOGENIZE
FINE DISPERSE DELIVERY SYSTEM
Flow chart for emulsion preparation

65. Methods of emulsion preparation: Continental or dry gum method:
Emulsifier is triturated with the oil in perfectly
dry porcelain mortar
water is added at once
triturate immediately, rapidly and continuously
(until get a clicking sound and thick white cream is formed,
this is primary emulsion)
the remaining quantity of water is slowly added to form the final emulsion

66. Example for dry gum method
Ingredients: Cod liver oil 50 ml
Acacia gm
Syrup ml
Flavor oil ml
Purified oil up to 100 ml
Method:
Accurately weigh or measure each ingredient. Place cod liver oil in dry mortar. Add acacia and give it a very quick mix. Add 25 ml of water and immediately triturate to form thick white , homogenous primary emulsion. Add flavor and mix. Add syrup and mix. Add sufficient water to total 100 ml.

67. English or Wet Gum Method
triturate gum with water in a mortar to form a mucilage
oil is added slowly in portions the mixture is triturated
after adding all of the oil, thoroughly mixed for several minute to form the primary emulsion
Once the primary emulsion has been formed remaining
quantity of water is added to make the final emulsion.

68. remaining quantity of water is added to make the final emulsion
Bottle or Forbes Bottle Method
- It is extemporaneous preparation for volatile oils or oil with low viscosity.
gum + oil (dry bottle)
Shake
water (volume equal to oil) is added in portions with vigorous shaking to form primary emulsion
remaining quantity of water is added to make the final emulsion

69. Auxiliary method
An emulsion prepared by other methods can also be improved by passing it through a hand homogenizer, which forces the emulsion through a very small orifice, reducing the dispersed droplet size to about 5 microns or less.

70. In situ soap method Calcium Soaps :
w/o emulsions contain oils such as oleic acid , in combination with lime water ( calcium hydroxide solution, USP).
Prepared by mixing equal volumes of oil and lime water.

71. In situ soap method – Example Nascent soap
Oil Phase : Olive oil / oleic acid ; olive oil may be replaces by other oils but oleic acid must be added.
Lime water : Ca(OH)2 should be freshly prepared.
The emulsion formed is w/o
Method of preparation : Bottle method
Mortar method : When the formulation contains solid insoluble such as zinc oxide and calamine.

72. Preparation of emulsions- large scale
Mechanical equipment for emulsification (Agitation)
Mechanical stirrers
-Propeller type mixers
-Turbine mixers
Homogenizers
Colloid mills
Ultrasonifiers

73. Paper:-910102 Jignasha R. Bhuria(2009-2010)
Flow of material:
SS Tank
100-10,000 L
Steam G.jacketed
SS Tank
Colloid mill L
Filtration
14,000 L
Filling & Sealing
60-80bottles\M
Inspection
40-60bootles/M
Distillation L
Washing
80-240bottles/M
Labelling
250labels/M
Paper: Jignasha R. Bhuria( ) 73
Pkg conveyor
cartoning

74. Mixing & Storage Tanks Manufactured from SS & is Argon welded.
The tank will be mounted on 4 legs with castors for movements.
Available from 50-10,000 liters.

75. SS Tank with Stirrer
With SS steam jacketed & insulation with SS cladding.
Different type of stirrer (paddle/ anchor/propeller) available.
Electric heating also possible for small scale.
Capacity:-100 ltres to 10,000ltrs

76. Jacketed kettle / SS Tank (steam, gas or electrically heated)

77. Homogenizer Outlet Homogenized liquid Spring Valve cover Valve seating
Crude mixture inlet

78. Colloid mill Superfine grinding
and simultaneous emulsifying, dispersing, and homogenizing within one process.
Clearance between rotor & stator: 0.001inch
Rotor speed: 2800 rpm
Continuous and recalculating method of operation possible
Jacket is provided for heating or cooling application .
Crude mixture inlet
Clearance
ROTER
Homogenized
liquid
Drive shaft

79. Ultrasonifier
Outlet
inlet
Orifice
Vibrating blade

80. Bottle washing machine

81. Bottle filling machine

82. ROTARY PISTON FILLING CUM SEALING MACHINE
Single Operator for Two Operations
Prevent Contamination – as immediate sealing of filled bottles
Accuracy + 0.5% due to piston dosing principle
Electronic liquid level controller & pneumatically regulated control valve

83. Bottle Inspection Machine

84. Automatic High Speed Labeling Machine
Application - Patch Body
Shape of Container: Flat/Elliptical/Oval/Square
Size of label: mm
Output: containers / minute

85. Packing conveyor belt

86. Bottle trimming & cartooning machine

87. Packing,Labelling And Storage
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.

88. The following are the quality control tests done for emulsions:
Quality control tests for Emulsions
The following are the quality control tests done for emulsions:
1. Determination of particle size and particle count: Determination of changes in the average particle size or the size distribution of droplets is an important parameter used for the evaluation of emulsions. It is performed by optical microscopy, sedimentation by using Andreasen apparatus and Coulter counter apparatus.
2. Determination of viscosity: Determination of viscosity is done to assess the changes that might take place during aging. Emulsions exhibit non-newtonian type of flow characterstics.
The viscometers which should be used include cone and plate viscometers.

89. 3. 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. 4. 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.

90. PRODUCT VALIDATION
Major test parameters used for final product testing
Appearance pH
Viscosity
Specific gravity
Microbial count
Leakage test for filled bottle
Check the cap sealing
Fill volume determination
Particulate matter testing
Stress test

91. REFERENCE
The Theory & Practice of Industrial pharmacy by Leon Lachman.
CVS Subrahmanyam , Textbook of Physical Pharmaceutics, edition 2007, Vallabh Prakashan,PP
Aulton, Michael E., ed (2007). Aulton's Pharmaceutics: The Design and Manufacture of Medicines (3rd ed.). Churchill Livingstone.
Ansel’s Pharmaceutical Dosage Forms and Drug Delivery Systems, 9th edition, pg no. 376
Validation of Disperse System: Pharmaceutical Dosage Form: Disperse Systems: Volume 3 (Part B).