The document discusses the HLB system for classifying emulsifying agents based on their hydrophilic-lipophilic balance. Emulsifying agents with HLB values between 3-6 produce water-in-oil emulsions, while those between 8-18 produce oil-in-water emulsions. It also describes common methods for preparing emulsions on a small scale, including the continental, English, and bottle methods. Factors that affect emulsion stability are creaming, coalescence, microbial deterioration, and physical or chemical changes over time. Proper use of emulsifiers, thickeners, preservatives, and storage conditions can help increase stability.
HISTORY, CONCEPT AND ITS IMPORTANCE IN DRUG DEVELOPMENT.pptx
(Emulsion 3)
1. Emulsions 3
Md. Saiful Islam
BPharm, MPharm (PCP)
North South University
Fb Group: Pharmacy Universe
2. The HLB system
• Generally ,each emulsifying agent has a hydrophilic
portion and a lipophilic portion
• A method has been devised whereby emulsifying or
surface-active agents are categorized on the basis of
their chemical makeup as to their hydrophil-lipophil
balance, or HLB
• By this method, each agent is assigned an HLB value or
number indicating the substance’s polarity
3. The HLB system
• Although the numbers have been assigned up to about
40, the usual range is between 1 and 20
• Materials that are highly polar have been assigned
higher numbers (8-18) and produce o/w emulsions
• Materials that are less polar and more lipophilic have
been assigned HLB values of (3-6) and produce w/o
emulsions
4. Activity and HLB value of surfactants
Activity Assigned HLB
Antifoaming 1-3
Emulsifiers (w/o) 3-6
Wetting agents 7-9
Emulsifiers (o/w) 8-18
Solubilizers 15-20
Detergents 13-16
5. Methods of emulsion preparation
Small scale preparation:
In the laboratory or pharmacy, emulsions may be prepared
using a dry porcelain mortar and pestle, a mechanical
blender or mixer, a hand homogenizer or sometimes a
simple prescription bottle.
In the small scale extemporaneous preparation of
emulsions, three methods may be used:
1) The continental or dry gum method
2) The English or wet gum method
3) The bottle or Forbes bottle method
6. The continental or dry gum method
- This method is referred to as the 4:2:1 method, in
which for every 4 parts by volume of oil,2 parts of
water and 1 part of gum are added to prepare primary
emulsion
- In this method, the acacia or other o/w emulsifier is
triturated with the oil in a perfectly dry porcelain morter
- A mortar with a rough inner surface is preferable
- After proper mixing of oil and gum, two parts of water
is added
7. The continental or dry gum method
- The mixture is triturated immediately, rapidly and
continuously until a creamy white primary emulsion is
produced and a crackling sound found with the
movement of pestle
- Generally about 3 minutes mixing is required to produce
a primary emulsion
- Liquid formulation ingredients soluble in external phase
then mixed to the primary emulsion
8. The continental or dry gum method
- Solid substances ( preservatives, stabilizers, colorants,
any flavouring material) dissolved in a suitable volume of
water added as a solution to the primary emulsion
- Any substance interfering the emulsion stability usually
added at the last
- After addition of all the necessary agents, the final
volume of the emulsion is made
- Sometimes the ratio of acacia is adjusted depending on
the nature of oil
9. English or wet gum method
• Same proportion of oil, water and gum are used as dry
gum method
• Only the order of mixing is different
• A mucilage of the gum is prepared by triturating the gum
with twice its weight of water
• The oil is added slowly in portions and the mixture is
triturated to emulsify the oil
10. English or wet gum method
• Additional water may be blended into the mixture before
adding another portion of oil, if it is too thick
• After all of the oil is added, the mixture is thoroughly
mixed for several minutes to ensure uniformity
• Then other formulative ingredients are added and the
emulsion is brought to the final volume
11. Bottle or Forbes bottle method
• Useful for preparation of emulsions from volatile oil or
oleaginous substances of low viscosities
• Powdered acacia is placed in a dry bottle and two parts
of oil is added
• The mixture is thoroughly shaken in the capped
container
• A volume of water ( App. equal to the volume of oil) is
added in portions and mixture is thoroughly shaken after
each addition
12. Bottle or Forbes bottle method
• After all of the water is added, the emulsion is diluted to
the proper volume with water or aqueous solution of
other formulative agents
Limitation:
• This method is not suitable for viscous oils because they
cannot be thoroughly agitated in the bottle when mixed
with emulsifying agent
13. In situ soap method
In this method:
- An oil containing sufficient free fatty acid, such as
linseed or olive oil, is placed in a suitable container
- An equal volume of alkali , such as calcium hydroxide
solution is added
- When the mixture is agitated, the fatty acid of the oil
reacts with the alkali to form a calcium soap which, in
turn, promotes a w/o emulsion
14. In situ soap method
- The emulsifying agent in this preparation is Ca salt of
free fatty acid which is formed in situ (at the time of
mixing)
- The method may be used to prepare either o/w or w/o
emulsions, depending on whether Na hydroxide or Ca
hydroxide solution is used
- Example: Calamine lotion
Lime liniments
15. Emulsion stability
• The most important property of pharmaceutical and
cosmetic emulsion is the stability of the finished product
• A stable emulsion is characterized by absence of –
- Flocculation and creaming
- Coalescence of the globules and separation of the
internal phase from the emulsion
- Deterioration by micro-organisms
And maintenance of elegance with respect to general
appearance, odor, color and consistancy
16. Emulsion stability
The types of instability in a pharmaceutical emulsion may
be classified as follows:
1) Flocculation and creaming
2) Coalescence and breaking
3) Deterioration by micro-organisms and
4) Miscellaneous physical and chemical changes
17. Flocculation and creaming
• Flocculation is the joining together of globules to form
large clumps
• The passage of an emulsion at a high pressure through
an orifice sometimes result in flocculation
• Creaming is the rising( upward creaming) or settling
(downward creaming) of globules to form a concentrated
layer at the surface or at the bottom of the emulsion
• Creaming results in a lack of uniformity of the product
and it may lead to lack of dose uniformity if container is
not agitated properly before administration
18. Flocculation and creaming
• Stokes’ equation includes the various factors involved in
the creaming process and density of the internal and
external phase is one of them
• Remedy:
• The equal density of both the phases will diminish the
creaming
• The velocity of creaming is reduced by increasing the
viscosity of the external phase
• The use of suitable thickening agent may reduce the
velocity of creaming
19. Coalescence and breaking
• Unlike creaming, the coalescence of globules and the
subsequent breaking of an emulsion are irreversible
process
• An broken emulsion, in which the phases have
separated as distinct layers, simple mixing fails to re-
establish the stable emulsion
• Today it is generally agreed that the most significant
element in stabilizing an emulsion against breaking is the
emulsifier film surrounding the dispersed particles
20. Coalescence and breaking
• Remedy:
• The tough and coherent film at the interface can with
stand the tendency of globules to coalesce and keep the
emulsion stable for the desired period of time
• The broken emulsion may be reconstituted only by
incorporating more emulsifying agent and passing the
product through the proper emulsifying machinery
21. Deterioration by micro-organisms
Molds, yeasts and bacteria may bring about
- the decomposition of emulsifying agents
- contaminate the aqueous phase
- produce rancidity in the oil and destroy oil soluble
vitamins
Emulsions are more contaminated by fungi ( molds and
yeasts) than by bacteria
22. Deterioration by micro-organisms
Remedy:
• Use of preservative ( particularly effective against molds,
yeasts and bacteria) can prevent the deterioration
• Combinations of parahydroxy benzoates-0.1 to 0.2% of
methyl ester and 0.02 to 0.05% of propyl ester-
frequently are used
• The presence of certain drugs, such as benzoic acid,
salicylic acid or high concentration of alcohol may also
provide adequate protection against micro-organisms
23. Miscellaneous physical and chemical
changes
• Care must be taken to protect emulsions against
deterioration caused by light, extreme temperature,
oxidative and hydrolytic rancidity of the oil
• Freezing causes coarsening and sometimes breaking of
an emulsion
• Light and rancidity affect the color and odor of the oils
and may destroy their vitamin activity
• Extreme temperature may cause breaking or inversion
( phase conversion) of an emulsion
24. Miscellaneous physical and chemical changes
Remedy:
• Emulsions stabilizing by synthetic emulsifier are
unusually resistant to extreme heat and cold
• Anti-oxidant are necessary to prevent rancidity
• Emulsions should be kept in tight containers, stored at
moderate temperature and kept in dark bottles( if light
sensitive)