Chapter 7.

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Dr. Bassam Elmadhoun Assistant Professor of Pharmaceutics

Surface active agents

Surface active agents

Are called amphiphiles or surfactants Are compounds have a tendency to accumulate at the boundary between two phases Their adsorption at interfaces results in changes in the nature of the interface which are of considerable importance in pharmacy

Uses of surfactants
Facilitate emulsion formation Enable insoluble particles to be dispersed in the form of suspension

Incorporation of Make solid surfaces insoluble compounds more readily wetted within micelles of the when adsorbed on their surfactant can lead to surfaces the production of clear solutions
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Many drugs are reported to be surface active due to their amphipathic nature of the drugs However, the hydrophobic portions of the drug molecules are more complex as composed of aromatic or heterocyclic ring system
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Examples of drugs have surface active property

Tranquillizers such as chlorpomazine has large tricyclic phenothiazine ring system
Antidepressant like imipramine having tricyclic ring

Antihistamines such as diphenhydramine which have diphenylmethane group

Surface activity
Head + Tail (hydrophilic head and hydrophobic tail Molecules at the surface of a liquid are not completely surrounded by other like molecules as they are in the bulk of the liquid

What is the status of molecules at the surface of the liquid?

Surface tension is a measure of the contracting power of the surface. So when we reduce the surface tension we reduce the contracting power of the surface.

How surfactant reduce the contracting power of the surface?

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Imbalance of attractive forces exists at the interface between two immiscible liquids. The value of the interfacial tension is generally between those of the surface tensions of the 2 liquids

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Micelle formation
The surface tension of surfactant solution decreases progressively with increase of concentration of surfactant molecules At certain concentration, the hydrophobic groups form aggregates (usually spherical) of colloidal dimensions called micelles
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What is the critical micelle concentration or CMC?

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How can we detect the onset of micelle formation?

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CMC increases
Increase in hydrophilic oxyethylene chain length e.g. non-ionic surfactant

CMC decreases
When hydrophobic chain length is increased Addition of electrolytes to ionic surfactant

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At CMC
The conc. of surfactant monomers in equilibrium with micelles stays constant

Above CMC
Addition any surfactant goes to form micelles

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Solubilization
The interior core of a micelle have the properties of a liquid hydrocarbon and thus capable of dissolving materials that are soluble in such liquids

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What is maximum additive concentration (MAC)?

Solubility

Concentration

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Pharmaceutical applications of Solubilization

A wide range of insoluble drugs has been formulated using the principle of Solubilization. Phenolic compounds such as cresol, chlorocresol, chloroxylenol and thymol are frequently solubilized with soap to form clear solutions which used widely for disinfection.
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Example # 1
Solubilization of iodine using nonionic surfactants (iodophors) which is more stable than iodine-iodide system. This solution used to disinfect instrument.

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Example # 2
Preparation of water-insoluble vitamins like A, D, E and K using non-ionic surfactant like polysorbate

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Example # 3
Solubility of steroidal opthalmic products using non-ionic surfactant as a means of producing clear solutions.

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Does the Solubilization affect drugs activity?

Low conc. of surfactant agents increase absorption due to enhanced contact with absorbing membrane Conc. Above CMC decrease absorption of drugs due to holding the drug into micelle.
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Solubilization and drug stability

Non polar drugs
Are protected more from hydrolysis. Why? Example: Benzocaine

Polar drug
Are less protected against hydrolysis. Why? Example: Homatropine

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Is there a difference in the protection characteristics between anionic surfactant and cationic surfactant?
In case of base-catalysed hydrolysis, OH- group is repulsed from anionic micelles than from cationic micelles and therefore, sent back away from affecting the drug.

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Detergency
Is a complex process where by surfactants are used to remove foreign matter from solid surface and removal of dirt from cloths or cleansing of body surface How? Wetting and Solubilization.

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Detergency
1- detergent have good wetting property so it will be in intimate contact with the surface. 2- detergent will lower the interfacial tension of dirt/water and dirt/solid. This result in reducing the work of adhesion between dirt and solid so that it will be easily removed. 3- the detergent can be adsorbed on dirt surface so the dirt will be solubilized or emulsified into water

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