نمر العصيمى
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(( Emulsions))
Definitions / types
Emulsions are heterogeneous systems consisting of two immiscible liquids,one of which (the disperse phase) is finely divided and distributed through the other (the continous phase),since this type of dispersion is unstable .an emulsifying agent is usually required to maintain the dispersion
و يعرف المستحلب أيضاً بأنه مزيج غير ثابت من سائلين غير ممتزجين و عامل استحلابي (emulsifying agent).
عملية دمج مكونات المستحلب تسمى بالاستحلاب (emulsification ).
عملية دمج مكونات المستحلب تسمى بالاستحلاب (emulsification ).
Emulsion consists of:
Dispersed phase (internal or discontinuous phase)
Dispersion medium (external phase or continuous phase)
Emulsifying agent
قطر كريات السائل المبعثر (dispersed phase ) عموما يتراوح بين 0.1-10 ميكرون.
و مع ذلك يمكن أن نجد مستحلبات فيها قطر الكريات 0.01 أو 100 ميكرون .
و مع ذلك يمكن أن نجد مستحلبات فيها قطر الكريات 0.01 أو 100 ميكرون .
يمكن اللجوء لعمل المستحلب عندما يتوجب علينا جمع سائلين غير ممتزجين في مستحضر واحد.. أحدهما قطبي (polar) و الثاني غير قطبي (nonpolar).
يصنف المستحلب إلى مجموعتين o/w و w/o:
When the continous phase is aqueous the system described as oil-in-water(o/w) emulsion
And when the continous phase is oily the system described as water-in-oil(w/o) emulsion
المستحلب المعد للاستخدام الداخلي( internal use ) يكون من نمط (o/w)
و المستحلب المعد للاستخدام الخارجي(external use) يمكن أن يكون بأحد الشكلين.
و المستحلب المعد للاستخدام الخارجي(external use) يمكن أن يكون بأحد الشكلين.
Creams are opaque, soft solids or thick liquids consist of medications that are dissolved or suspended in water removable (i.e., vanishing cream) or emollient b ases
.
.
و الكريمات معدة للاستعمال الخارجي و يمكن أن تكون من احد النمطين المذكورين.
الكريمات تستخدم عادة في حالات الإصابات الرطبة (weeping lesions) ذلك أن للكريمات أثر مجفف نوعاً ما و يمتزج مع السوائل الخارجة من الإصابة.
الكريمات تستخدم عادة في حالات الإصابات الرطبة (weeping lesions) ذلك أن للكريمات أثر مجفف نوعاً ما و يمتزج مع السوائل الخارجة من الإصابة.
Lotions are fluid emulsions or suspensions designed for external applications.
They have a lubricating effect and thus are applied to intertiginous areas, that is, areas
where the skin rubs together, such as between the fingers, between the thighs, or under the arms.
Applications:
-Topical creams or lotions are popular forms of emulsions for external use,
-Internally, emulsions are used to dispense oil and aqueous drugs together, to mask the taste of unpleasant oily drugs, and sometimes to enhance the absorption of selected drugs.
-Internally, emulsions are used to dispense oil and aqueous drugs together, to mask the taste of unpleasant oily drugs, and sometimes to enhance the absorption of selected drugs.
-intravenously administered lipid emulsion used to administer high calories to severly debilitated patients.
]Composition
Emulsions generally contain three components:
Emulsions generally contain three components:
A lipid phase
An aqueous phase
An emulsifier
The compounding pharmacist has the greatest flexibility in the choice of an emulsifier. Common emulsifiers are listed as the following :
Emulsifiers and stabilizers for use in emulsions:
Carbohydrates:
Acacia , Agar , Chondrus , Pectin , Tragacanth.
Proteins:
Casein , Egg yolk , Gelatin.
High molecular weight alcohols:
Cetyl alcohol , Glyceryl monostearate , Stearyl alcohol.
Surfactants:
Anionic , Cationic , Nonionic.
Solids:
Aluminum hydroxide , Bentonite , Magnesium hydroxide
Emulsion preparation:
emulsification is an energy consuming process,this energy can
be brought either by mechanicalor manual agitation,ultrasonic
vibration or heat
.
.
the commonly used techniques in emulsion preparation are morter and pestle,electric mixer,hand homogenizer and beakers
*two main methods for manual emulsion preparation using morter and pestle are:
1-English method(wet gum method):
the ratio of oil,water and emulsifier is 41 respectively for primary emulsion .
the water and emulsifier is put into a rough surface morter,then the oil is added in small quantities with rapid trituration until the primary emulsion formed, additional water can be added slowly with trituration.
the ratio of oil,water and emulsifier is 41 respectively for primary emulsion .
the water and emulsifier is put into a rough surface morter,then the oil is added in small quantities with rapid trituration until the primary emulsion formed, additional water can be added slowly with trituration.
2-continental method(dry gum method):
the same ratio as before.the emulsifier is mixed with the oil,then the water is added in one time wih very rapid tritiuration until the emulsion is formed,additional water can be added slowly with trituration.
the beaker method :
it is often used for creames and lotions:
1-the ingradients are divided into two parts ,the oil with oil soluble
ingradients,and the water with water soluble ingradients
ingradients,and the water with water soluble ingradients
2-each phase is heated seperately to about 60-70 c,then the internal phase is added to the other phase with stirring
3- the product is allowed to cool gradually while stirring until the emulsion is formed and cooled.
Emulsifying agents:
The emulsifiers is intended to minimize the tendency of globules to coalesce together to form a large globules,the stability of an emulsion is dependant on the properties of rhe emulsifier.
Emulsifying agents may be-
Surface active agents(surfactants),hydrophilic colloids,or finely divided solid particles.
All r working at the oil-water interface resulting finally in formation of amicrofilm surrounding the oil globule resulting in its dispersion
All r working at the oil-water interface resulting finally in formation of amicrofilm surrounding the oil globule resulting in its dispersion
HYDROPHIL-LIPOPHIL BALANCE(HLB):
HLB is a describing scale system of the surfactants-
-each surfactanthas HLB value which is determined
experimentally,this value indicates the relative number of hydrophilic groups to the lipophilic ones in the surfactant molecule.
experimentally,this value indicates the relative number of hydrophilic groups to the lipophilic ones in the surfactant molecule.
-the higher the HLB value,the larger number of hydrophilic groups and hence the more hydrophilic properties of the surfactant.
HLB value:
antifoaming agents 1-3
emulsifying agents(w/o emulsion) 3-6
wetting agents 7-9
emulsifying agents(o/w emulsion) 8-18
detergents 13-16
solubilizing agent 16-18
BLENDING OF SURFACTANTS
:
:
غالبا مايكون استخدام اكثر من عامل استحلابى بينتج عنة مستحلب اكثر ثباتا
because the HLB numbers are additive,the HLB value of ablend can be readily calculated
ومن الممكن جمع اكثر من عامل استحلابى عن طريق النسبة والتناسب
for example:
if 20ml of an agent with an HLB value of 9.65 is required ?
then two surfactants one with HLB value of 8.6
and one with HLB value of 12.8, can be blended in 3:1 ratio& the following quantities of each surfactant will be required
3\4 * 8.6 = 6.45(15ml)
1\4 * 12.8 =3.20(5 ml)
total HLB = 9.65(20ml)
to calculate the HLB required for the emulsifier in the formulation below, the following method is used:
to calculate the HLB required for the emulsifier in the formulation below, the following method is used:
petrolatum ..... 25g .... 56(25g\45g) *.... 8 = 4.5(portion of HLB)
cetyl alc. ..... 20g .... 44(20G\45G) *..... 15 = 6.7(portion of HLB)
N.B ( 56 & 44 r the % of oil phase and 8 & 15 r the required HLB).
emulsifier ..... 2g .
preservative ..... 0.2g .
pure water qs ad .... 100g .
Approximate HLB value for emulsifier = 4.5+ 6.7=11.2
PRESERVING AN EMULSION
-المستحلب من السهل ان يكون وسط لنمو البكتريا, وهذا من السهل حدوثة اما اثناء التحضير او اثناء الاستخدامز وبالتالى فمن الافضل ان يكون مكان التحضير والادوات المستخدمة يجب ان تكون نظيفة وغير ملوثة
وبالرغم من ذلك فاذا كان المستحلب سيتم الاحتفاظ بة لفترة طويلة فعلينا استخدام مادة حافظةزوالتى يجب ان تتمتع ببعض الخواص:
-It must be non-toxic,stable.compatible and inexpensive,,in addition :it must have an acceptable taste .odor and color
it also should be effective against a wide variety of bacteria,fungi and yeasts
-المادة الحافظة يجب ان تكون مركزة فى الوسط المائى للمستحلب(aqueous phase) لان النمو الطبيعى للبكتريا يكون فى هذا الوسط
because of nonionized form of the preservative is more effective against bacteria than the ionized form,so most of the preservative should be in the nonionized state
*to be effective,the preservative must be neither bound nor absorbed to any agent in the emulsion or the container
.
***the parabens(methyl paraben ,propyl paraben,butyl paraben) are considered to be some of the most satisfactory preservatives for emulsions
.
OILS AND FATS can become rancid,which causes the product to have an unpleasant odor,appearance and taste.antioxidants can prevent rancidity
.
***the parabens(methyl paraben ,propyl paraben,butyl paraben) are considered to be some of the most satisfactory preservatives for emulsions
.
OILS AND FATS can become rancid,which causes the product to have an unpleasant odor,appearance and taste.antioxidants can prevent rancidity
examples of antioxidants used in emulsion:
-ascorbic acid
FLAVORING AN EMULSION:
-when selecting an appropriate flavoring agent,the pharmacist should take into consideration the dispersion medium(external phase) of the emulsion
* for example: If a flavoring oil is used and most of the oil partitions into the internal phase as an oil in water emulsion,the flavor will be reduced in strength -oils can be incorporated by using small quantities of surfactants(usually surfactants with HLB value of 15 to 18 are used)…often in conjunction with asurfactant with HLB value in the range 8 to 12
**As a general Rule::
-it is necessary to have from 3 to 5 times as much surfactant as oil(flavoring) to ensure solubilization
-for best results:the oil should be mixed with the surfactants before it is added to the aqueous phase.
***Because this technique can cause the flavor to lose some of its potency,another approach is to use acosolvent system to incorporate the flavor.the use of ethanol,glycerin,or some appropriate solvent often provides acceptable results
. Packaging,Storage,Labeling: -it is important to package emulsions in tight containers to minimize the evaporation of water from the product
-emulsions should be stored at room temperature or refrigerated.
-their label should include the instruction shake well.
-their label should include the instruction shake well.
Stability
:
*the stability of emulsion can be enhanced by
*the stability of emulsion can be enhanced by
1-decreasing the globule size of the internal phase
2-obtaining an optimum ratio of oil in water
3-increasing the viscosity of the systemif the size of the globule is reduced to less than 5 micro M ,the stability and dispersion of the emulsion will increase(this reduction can be accomplished both with the shearing action of amortar and pestle with ahomogenizer
-
as the percentage of the internal phase increases,the viscosity of the product will also increase.
as the percentage of the internal phase increases,the viscosity of the product will also increase.
** alinear relationship exists between the viscosity of the emulsion and the viscosity of continous or external phase,,the viscosity of an emulsion generally increases on aging
**To improve the viscosity,the pharmac
ist can add a substance that is soluble in or miscible with the external phase of the emulsion
ist can add a substance that is soluble in or miscible with the external phase of the emulsion
EX: In case of o/w emulsions:hydrocolloids can be used,,,whereas for w/o emulsions,waxes and viscous oils as well as fatty alcohols and fatty acids are appropriate.
\THE EMULSION IS STABLE WHEN:
It retains its original appearance,odor,color and other physical properties and when no creaming or coalescence occurs
.
**من المشاكل التى تواجة الصيدلى عند تحضير المستحلب والتى تؤثر على ثباتة:
**من المشاكل التى تواجة الصيدلى عند تحضير المستحلب والتى تؤثر على ثباتة:
1-CREAMING:
وهذا يحدث عندما تتجمع الجزيئات وتتركز فى طبقة معينة فى المستحلب
وهذة الظاهرة تؤدى الى التوزيع غير المتكافىء للدواء(المادة الفعالة) فى المستحلب
-In
o/w emulsions,creaming can be identified when one sees the oil globules gather and rise to the top
وهذة الظاهرة تؤدى الى التوزيع غير المتكافىء للدواء(المادة الفعالة) فى المستحلب
-In
o/w emulsions,creaming can be identified when one sees the oil globules gather and rise to the top
-creaming is easily reversible because the dispersed globules are still surrounded by the protective film
.
**فى بعض الاحيان يكون رج المستحلب سبب فى اعادة توزيع جزيئاتة
.
**فى بعض الاحيان يكون رج المستحلب سبب فى اعادة توزيع جزيئاتة
***
three methods that r used to minimize creaming
:
three methods that r used to minimize creaming
:
1-to enhance the viscosity of the external aqueous phase
2-to reduce the size of the globules to avery fine state with ahomogenizer
3-to adjust the denisities of both the internal and the external phases so that their densities are the same,,thus ,neither phase would tend to rise to the top or settle at the bottom
.2-COALESCENSE
:
:
-contrary to creaming,,coalescence is an irreversible process becausethe film that surrounds the individual globules is destroyed
**altering the viscosity may help to stabilize globules and minimize their tendency to coalesce.
3-PHASE INVERSION:
-it occurs when an emulsion inverts from one form to another(from o/w to w/o and vice versa)
**monovalent cations tend to form o/w emulsion,,whereas divalent cations tend to form w/o emulsion.
EX:
EX:
-if sodium stearate is used to form o/w emulsion and then a calcium salt is added to form calcium stearate,,.The emulsion inverts from an o/w to a w/o type
4-flocculation
¯flocculation, an aggregation process. Flocculation occurs
when there is a net attractive force between droplets which is large enough to
overcome thermal agitation and cause persistent aggregation
when there is a net attractive force between droplets which is large enough to
overcome thermal agitation and cause persistent aggregation
- Whilst the droplets are held together they are not in intimate contact and are usually
separated by a layer of polymer or surfactant
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separated by a layer of polymer or surfactant
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