Surfactants, Their Types And Properties.pdf

SURFACTANTS, THEIR TYPES AND PROPERTIES 1

SANA JAVED PHARM. D M.PHIL PHARMACEUTICS Ph.D. PHARMACEUTICS (scholar)

TERMINOLOGIES English

Greek

Latin

oil

lipo-

oleo

water

hydro

Aqua

solvent

lyo

solvo

both

amphi

flow

Rheo

Affinity

Philic

Lack of affinity

Phobic

Nature

Pathic

science

logy

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TERMINOLOGIES Hydrophilic = with affinity for water  Lipophilic = with affinity for oil  Lyophilic = with affinity for the solvent  Lyophobic = lack of affinity for the solvent  Amphipathic = combining both natures (oil and water)  Amphiphilic = with affinity for both (oil and water). Such molecules are commonly termed “surfactants”, OR surface-active agents. 

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SURFACTANTS Surfactants are termed as • Surface-active agents • Wetting agents • Emulsifying agents or • Suspending agents depending on its properties and use.  Surfactants are monomers, it has a characteristic structure possessing both hydrophobic groups (water-hating) / non-polar regions (their "tails") usually contain a C12– C18 hydrocarbon chain and hydrophilic groups (water-liking) / Polar Regions(their "heads").  Therefore, they are soluble in both organic solvents and water.

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SURFACTANTS 

Example sodium dodecyl sulfate

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SURFACTANTS 

The existence of two such moieties in a moecule is referred to as amphipathy and the molecules are consequently often referred to as amphipatic molecules.

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EXAMPLES OF POLAR AND NON POLAR GROUPS Hydrophilic / Polar group (head) The hydrophilic regions can be anionic, cationic, zwitterionic, or non ionic. Surfactants are generally classified according to the nature of hydrophilic group..     

 

-Hydroxyl group (OH) -Aldehydic group (CHO) -Carboxylic group(COOH) -Sulfate ester -Nitro group (NO2) -Amine group (NH2) -Halogen (CL or Br)

Hydrophobic / Non-polar group / (tail) 

 

-saturated or unsaturated hydrocarbon chains (CH3-CH2-CH2---) Branching alkyl chains -Aromatic ring such as benzene or naphthalene

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TYPES OF SURFACTANT Depending on their charge characteristics, surfaceactive molecules may be  Anionic  Cationic  Non-ionic  Zwitterionic (amphoteric). 

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TYPICAL HYDROPHILIC GROUPS Anionic carboxylates: -COOsulfonates: -SO3sulfates: -OSO3phosphates: -OPO32Amphoteric betaine: N+(CH3)2CH2COO-

Cationic Quarternary ammonium salts N+(CH3)3Cl-

Nonionic polyoxyethylene group 9

Class Anionic

SURFACTANT

Examples •Na stearate •Na dodecyl sulfate CLASSIFICATIONS •Na dodecyl benzene sulfonate

-

CH3(CH2)16COO Na CH3(CH2)11SO4 - Na + CH3(CH2)11C6H4SO3- Na+

Cationic

CH3(CH2)11NH3+ Cl•Laurylamine hydrochloride •Trimethyl C12H25N +(CH3)3Cl_ dodecylammonium chloride •Cetyl trimethylammonium CH3(CH2)15N +(CH3)3Brbromide

Non-ionic

•Polyoxyethylene alcohol •Alkylphenol ethoxylate •Polysorbate 80

CnH2n+1(OCH2CH2)mOH C9H19–C6H4–(OCH2CH2)nOH

Zwitterionic

•Dodecyl betaine •Lauramidopropyl betaine •Cocoamido-2hydroxypropyl sulfobetaine

C12H25N +(CH3)2CH2COOC11H23CONH(CH2)3N+ (CH3)2CH2COOCnH2n+1CONH(CH2)3N+ (CH3)2CH2CH(OH)CH2SO3-

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CLASSIFICATION AND APPLICATIONS OF SURFACTANTS





Anionic surfactants In solution, the head is negatively charged.

The most commonly encountered anionic surfactants have carboxylate, sulfate, sulfonate and phosphate polar groups in combination with counterions such as sodium, potassium calcium and magnesium

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CLASSIFICATION AND APPLICATIONS OF SURFACTANTS

Anionic surfactants Amongst the different classes of surfactants, anionic surfactants are the most widely used type of surfactant for preparing shampoos because of its excellent cleaning properties and high hair conditioning effects.  Anionic surfactants are particularly effective at oil cleaning and oil/clay suspension. 

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ANIONIC SURFACTANTS Sodium Lauryl Sulfate BP  is very soluble in water at room temperature, and is used pharmaceutically as a preoperative skin cleaner, having bacteriostatic action against Gram-positive bacteria, and also in medicated shampoos  is a component of emulsifying wax. (fast track)

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CATIONIC SURFACTANTS In solution, the head of the cationic surfactant is positively charged.  Cationic surfactants are quaternary ammonium compounds and they are mostly used for their disinfectant and preservative properties as they have good bactericidal properties.  They are used on skin for cleansing wounds or burns.  Their aqueous solutions are used for cleaning contaminated utensils. 

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CATIONIC SUFRACTANTS Mostly used cationic surfactants are cetrimide, benzalkonium chloride and cetylpyridinium chloride

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NON-IONIC SURFACTANTS These surfactants do not have any electrical charge.  They are less irritant than other anionic or cationic surfactants.  The hydrophilic part contains the polyoxyethylene ,polyoxypropylene or polyol derivatives.  The hydrophobic part contains saturated or unsaturated fatty acids or fatty alcohols  They are excellent grease/oil removers and emulsifiers. 

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NON-IONIC SURFACTANTS

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NON-IONIC SURFACTANTS The non ionic surfactant can be classified as  The Polyol esters includes glycol and glycerol esters and sorbitan derivatives. 



Polyoxyethylene esters includes polyethylene glycol (PEG 40,PEG -50 PEG- 55). Poloxamers They are supplied commercially as Pluronics

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NON-IONIC SURFACTANTS One advantage over ionics is that the length of both the hydrophilic and hydrophobic groups can be varied to obtain maximum efficiency in use.  They are extensively used to produce both o/w and w/o emulsions for internal as well as external use 

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HYDROPHILIC-LIPOPHILIC BALANCE (HLB) 

surfactants contain both hydrophilic groups and lipophilic groups with one or the other being more predominant, the hydrophilelipophile balance (HLB) number is used as a measure of the ratio of these groups. It is a value between 0-40 defining the affinity of a surfactant for water or oil. HLB value of nonionic surfactants ranges from 0-20. HLB numbers >10 have an affinity for water (hydrophilic) and number <10 have an affinity of oil (lipophilic).

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HYDROPHILIC-LIPOPHILIC BALANCE (HLB)

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ZWITTERIONIC AND AMPHOTERIC SURFACTANTS Zwitterionic and amphoteric surfactants possess polar head groups which on ionisation may impart both positive and negative charges. The positive charge is almost always carried by an ammonium group and the negative charge is often a carboxylate. (it may be sulphate or sulphonate)  These surfactants have excellent dermatological properties. They are frequently used in shampoos and other cosmetic products, and also in hand dishwashing liquids because of their high foaming properties. 

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NATURAL SURFACTANTS

Eggs

Proteins

Lanolin

e.g. milk casein

w/o emulsifier

Plant extracts: leaves, seeds, stems E.g. Entana spiralis (locally known as beluru/sintok)

DEFINITION OF SURFACE TENSION: • The molecules at the surface are attracted by molecules from inside, whereas no force from outside the surface. Hence the resulting force is towards the interior of the liquid. This creates some internal pressure and forces liquid surfaces to contract to the minimal area. 



•Surfactants: are substances that absorb to surfaces or interfaces, causing a marked decrease in the surface tension.

• The surface tension then causes drops of liquid to be round since the surface of the liquid is being minimized that way.

INTERFACE 

Surface-active agents are organic molecules that, when dissolved in a solvent at low concentration, have the ability to adsorb (or locate) at interfaces, thereby altering significantly the physical properties of those interfaces.

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INTERFACE

The term “interface” is commonly employed here to describe the boundary in liquid/liquid, solid/liquid and gas/liquid systems  This adsorption behavior can be attributed to the solvent nature and to a chemical structure for surfactants that combine both a polar and a non-polar (amphiphilic) group into a single molecule. To accommodate for their dual nature, amphiphiles therefore “sit” at interfaces so that their lyophobic moiety keeps away from strong solvent interactions while the lyophilic part remains in solution. 

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REDUCTION OF SURFACE AND INTERFACIAL TENSION When surfactants are dissolved in water they orientate at the surface so that the hydrophobic regions are removed from the aqueous environment, as shown in Figure.  The reason for the reduction in the surface tension when surfactant molecules adsorb at the water surface is that the surfactant molecules replace some of the water molecules in the surface and the forces of attraction between surfactant and water molecules are less than those between two water molecules, which results in a tendency for the surface to contract. 

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REDUCTION OF SURFACE AND INTERFACIAL TENSION Surfactants will also adsorb at the interface between two immiscible liquids such as water and oil and will orientate themselves as shown in Figure , with their hydrophilic group in the water and their hydrophobic group in the oil. The interfacial tension at this interface, which arises because of a similar imbalance of attractive forces as at the water surface, will be reduced by this adsorption.  There is an equilibrium between surfactant molecules at the surface of the solution and those in the bulk of the solution which is expressed by the Gibbs equation 

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REDUCTION OF SURFACE AND INTERFACIAL TENSION The surface activity of a particular surfactant depends on the balance between its hydrophilic and hydrophobic properties. For a homologous series of surfactants:  An increase in the length of the hydrocarbon chain (hydrophobic) increases the surface activity. This relationship between hydrocarbon chain length and surface activity is 

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REDUCTION OF SURFACE AND INTERFACIAL TENSION 

expressed by Traube’s rule, which states that ‘in dilute aqueous solutions of surfactants belonging to any one homologous series, the molar concentrations required to produce equal lowering of the surface tension of water decreases threefold for each additional CH2 group in the hydrocarbon chain of the solute’.

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MICELLIZATION When an amphiphile or surface active agent is present in a liquid (solvent) in low concentrations it forms a true or ionic solution.  As the concentration is increased, aggregation occurs over a narrow concentration range.  These aggregates which may contain 50 or more monomers are called micelles and the process is called micellization. 

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MICELLIZATION

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MICELLIZATION CRITICAL MICELLE CONCENTRAION (CMC)

The concentration of monomers at which the micelles form is known as micellization. Or  The critical micelle concentration is the point at which surfactant molecules aggregate together in the liquid to form groups known as micelles.  The main reason for micelle formation is the attainment of a minimum free energy state. Micelles only form above critical micelle temperature.  For example, the value of CMC for sodium dodecyl sulfate in water (no other additives or salts) at 25 °C, atmospheric pressure, is 8x10−3 mol/L.

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MICELLIZATION Aggregation Number The number of monomers that aggregate to form micelles is known as aggregation number. Kraft temperature: The Krafft temperature (also known as Krafft point, or critical micelle temperature) is the minimum temperature at which surfactants form micelles. It is named after German chemist Friedrich Krafft. Below the Krafft temperature, there is no value for the critical micelle concentration (CMC), i.e., micelles cannot form. 35

MICELLIZATION 







Explanation:The phenomenon of micelle formation can be explained as follows. Below the CMC, the concentration of surfactant (amphiphile) added undergoes adsorption at the air _water interface. As the total concentration of amphiphile is raised, eventually a point is reached at which both the interface and the bulk phase become saturated with Monomers. This is the critical micelle concentration. Any further amphiphile added in excess of this concentration aggregates to form micelles in the bulk phase and in this manner, the free energy of the system is reduced.

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MICELLIZATION

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MICELLIZATION

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water

MICELLIZATION

oil

Orientation Of Amphiphiles. Orientation of amphiphile depends upon the solvent which may be polar i.e, aqueous or non-polar. Orientation In Aqueous Medium. In case of amhiphiles in water, the hydrocarbon chains (non_polar) face inward into the micelle to form their own hydrocarbon environment. Surrounding this hydrocarbon core are the polar portions of the amphiphiles assosiated with the water molecules of the continuous phase. 39

MICELLIZATION 

Orientation In Non_polar Medium. The orientation of the molecules is now reversed, with the polar heads facing inwards while the hydrocarbon cahins are associated with the continuous non_polar phase. (reverse or inverted micelles) Non_polar solvent

water

oil

water

Reverse micelles

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TYPES OF MICELLES WATER WATER

WATER

WATER Spherical

Laminar

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TYPES OF MICELLES 1.Spherical micelles Spherical types of micelles exist at and just above the critical micelle concentration. Most surfactants of pharmaceutical interest fall into this category 2. Cylinderical micelles The micelles elongating to form cylindrical structures

3.Laminar micelles. At high concentrations, laminar micelles have an increasing tendency to form and exist in equilibrium with the spherical micelles.

Ref: cooper and Gunn’s tutorial pharmacy

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GEGENIONS Note: Gegenions :a certain number of the sodium ions are attracted to the surface of the micelle,reducing the overall charge .these bound ions are caled gegenions.

Na+ Na+

Na+

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MICELLISATION  



PROPERTIES OF MICELLES Micelles are formed at the CMC. Most micelles are spherical and contain between 60 and 100 surfactant molecules. There is an dynamic equilibrium between micelles and free surfactant molecules in solution. They are continually formed and broken down in solution – they should not be thought of as solid spheres.

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MICELLISATION PROPERTIES OF MICELLES  The typical micelle diameter is about 2–3 nm and so they are not visible under the light microscope.  When the surfactant concentration is increased above the CMC, the number of micelles increases but the free surfactant concentration stays constant at the CMC value.

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STRUCTURE OF THE MICELLES

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VARIATION IN PHYSICAL PROPERTIES BELOW AND ABOVE THE CMC VALUE.

OF SURFACTANT SOLUTIONS

The effect of micellization on some of the physical properties of solutions containing surface active agents or amphipiles is shown. The surface tension decreases upto the cmc. Above the cmc, the surface tension remains essentially constant showing that the interface is saturated and micelle formation has taken place in the bulk phase.

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FACTORS AFFECTING CMC 1. Th Hydrocarbon Chain a. Chain length : Increase in length of the hydrocarbon chain results in  A logarithmic decrease in CMC  corresponding increase in micellar size.

Increase length  Increased hydrophobicity  Decreased cmc

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FACTORS AFFECTING CMC b. Branched hydrocarbon chain. Branching of a hydrocarbon chain causes an increase in cmc since the decrease in free energy arising from the aggregation of branched chain molecules is less than that obtained with linear molecules with the same number of carbon atoms. linear molecule

branched chain molecule 53

FACTORS AFFECTING CMC c. Unsaturation. The CMC is increased by about 3_4 times by the presence of one double bond when compared with the value for the analogous saturated compound. The Hydrophilic Group a. Number of hydrophilic groups The electrical repulsive force between the adjacent ions in a micelle increases as the number of ionic goups increases. In addition an increase in the number of type of hydrophilic group increases the solubility of the surface active agent (means monomers are more soluble in the solution and have less tendency to agregate).Both these effects will lead to an increase in the CMC. 

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FACTORS AFFECTING CMC b. Position of hydrophilic group The cmc tends to increase as the polar group is moved from the terminal position towards the mid of the hydrocarbn chain. c. Nature of the hydrophilic group  Not involve any electrical work

 Much lower CMC and higher aggregation number  Increase in the ethylene oxide chain length

 Make more hydrophilic and the CMC increases 55

FACTORS AFFECTING CMC Type of counterion  Micellar size increases for a particular cationic surfactant as the counterion is changed according to the series Cl− < Br− < I−, and for a particular anionic surfactant according to Na+ < K+ < Cs+.

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FACTORS AFFECTING CMC Addition of electrolytes  Electrolyte addition to solutions of ionic surfactants decreases the CMC and increases the micellar size. This is because the electrolyte reduces the forces of repulsion between the charged head groups at the micelle surface, so allowing the micelle to grow.

Decrease

Increase 57

FACTORS AFFECTING CMC Effect of temperature Varies with type of surfactant molecule  Aqueous solutions of many non-ionic surfactants become turbid at a characteristic temperature called the cloud point.  At temperatures up to the cloud point there is an increase in micellar size and a corresponding decrease in CMC. (Non-ionic surfactants have cloud points above 100o C. The process is reversible; that is cooling the solution restores clarity. The turbidity at the cloud point is due to separation of the solution into two phases.)  Temperature has a comparatively small effect on the micellar properties of ionic surfactants.

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FACTORS AFFECTING CMC

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SOLUBILISATION Solubilisation Solubilisation is the process whereby water-insoluble or partly soluble substances are brought into solution by incorporation into micelles. Solubilizate Solubilized substance or the substance whose solubility is increased by micellar involvement in a solution is called……. Micellar solubilization (solubilization) is the process of incorporating the solubilizate (the component that undergoes solublization) into or onto micelles. Ref: Bentlys and Alexender T florence and david attwood

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SOLUBILISATION

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SOLUBILISATION Maximum additive concentration (MAC).  The maximum amount of solubilisate that can be incorporated into a given system at a fixed concentration is termed the maximum additive concentration (MAC).  Determination of Maximum additive concentration (MAC). The simpest method of determining the MAC is to prepare a series of vials containing surfactant solution of known concentration. Incresaing concentrations of solubilisate are added and the vials are then seaed and agitated untill eqilibrium conditions are achieved. The maximum concentratin of solubilisate forming a clear soution can be determined by visual inspectio or from extinction or turbidity measurement on the solutions.

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DETERMINATION OF MAXIMUM ADDITIVE CONCENTRATION (MAC).

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SOLUBILISATION The site of solubilisation within the micelle is closely related to the chemical nature of the solubilisate  Non-polar solubilisates (aliphatic hydrocarbons) or completely water insoluble hydrophobic molecules are dissolved in the hydrocarbon core of ionic and non-ionic micelles. 

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SOLUBILISATION 

Hydrophilic solubilisates or polar solubilzates can be adsorbed on the surface of the micelle.

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SOLUBILISATION Amphipathic solubilizates or  Solubilisates with intermediate hydrophobilcities or  Water-insoluble compounds containing polar groups are orientated in the palisade layer with the polar group at the core– surface interface of the micelle, and the hydrophobic group buried inside the hydrocarbon core of the micelle.(mixed micellization) 

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SOLUBILISATION 

In addition to these sites, solubilisation in non-ionic polyoxyethylated surfactants can also occur in the polyoxyethylene shell (palisade layer) which surrounds the core.

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SOLUBILISATION

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SOLUBILISATION Co-micellization  Solubilization can occur only in the presence of micelles.  Sometimes apmphipaths form micelles in the absence of solubilizate and occasionaly due to addition of solubilzate micelle formation occurs.  Addition of an amphiphilic solubilizate to amphipath may reduce the CMC to form mixed micelles and the process is called Comicellization

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SOLUBILISATION 

Hydrotrophy. Sometimes a fourth substance other than amphipath, water and solubilizate is added to increase the solubility of solubilizate. This effect of non-micelle forming amphipaths is known as hydrotrophy.

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SOLUBILISATION 

A hydrotrope is a compound that solubilises hydrophobic compounds in aqueous solutions (by means other than micellar solubilization). Typically, hydrotropes consist of a hydrophilic part and a hydrophobic part (like surfactants) but the hydrophobic part is generally too small to cause spontaneous self-aggregation. Hydrotropes do not have a critical concentration above which self-aggregation 'suddenly' starts to occur (as found for micelle, which have a critical micelle concentration or cmc). Instead, some hydrotropes aggregate in a step-wise self-aggregation process, gradually increasing aggregation size. Hydrotropes are in use industrially. Examples of hydrotropes include urea, sodium benzoate, sodium citrate, niacinamide and xylenesulfonate.

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SOLUBILISATION Factors affecting solubilisation Nature of the surfactant  When the solubilisate is located within the core or deep within the micelle structure the solubilisation capacity increases with increase in alkyl chain length up to about C16; further increase has little effect on solubilisation capacity.  Solubilisation decrease with chain branching  Increase in micellar radius favors the entry of solubilized molecules in micelles 73

FACTORS AFFECTING SOLUBILISATION 

The effect of an increase in the ethylene oxide chain length of a polyoxyethylated non-ionic surfactant on its solubilising capacity is dependent on the location of the solubilisate within the micelle and is complicated by corresponding changes in the micellar size. The aggregation number decreases with increase in the hydrophilic chain length so there are more micelles in a given concentration of surfactant and, although the number of molecules solubilised per micelle decreases, the total amount solubilised per mole of surfactant may actually increase.

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FACTORS AFFECTING SOLUBILISATION Solubilisation capacity of a series of polyoxyethylated non- ionic surfactants with a hydrocarbon chain lenghth of 16 and an increasing number of ethylene oxide units (E) surfactant

Aggregation number

Micelles per mole(10-12 )

C16 E17

99

6.1

C16 E32

56

10.8

C16 E44

39

15.4

C16 E63

25

24.1

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FACTORS AFFECTING SOLUBILISATION Nature of the solubilisate  A decrease in solubilisation occurs when the alkyl chain length of homologous series of solubilisates is increased. 



Unsaturated compounds are generally more soluble than their saturated counterparts.

Branching of the hydrocarbon chain of the solubilisates has little effect, but increased solubilisation is often noted following cyclisation. 76

FACTORS AFFECTING SOLUBILISATION A very lipophilic solubilisate will mainly reside in the micelles rather than in the aqueous phase surrounding them. This compound will therefore have a high micelle/water partition coefficient and also a high octanol/water partition coefficient.  On the other hand a hydrophilic compound will be partitioned mainly in the aqueous phase rather than the micelles and will have a low micelle/water and octanol/water partition coefficient  A relationship between the lipophilicity of the solubilisate, expressed by the partition coefficient between octanol and water, and its extent of solubilisation has been noted for several surfactant systems. 

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FACTORS AFFECTING SOLUBILISATION Temperature  With most systems the amount solubilised increases as temperature increases.  This increase is particularly pronounced with some non-ionic surfactants where it is a consequence of an increase in the micellar size with temperature increase.  In some cases, although the amount of drug that can be taken up by a surfactant solution increases with temperature increase, this may simply reflect an increase in the amount of drug dissolved in the aqueous phase rather than an increased solubilisation by the micelles.

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METHOD OF PREPARATION OF SOLUBILISED SYSTEMS Shake Flask

• Excess solid drug is equilibrated with the micellar solution

Melt Loading

• co-mixing the drug and surfactant at elevated temperature (typically about 60°C) and adding the resultant intimate mixture to water or buffer to form the solubilised micellar solution

Dialysis

• Drug and surfactant are dissolved in a watermiscible organic solvent followed by dialysis against water until the organic phase is replaced with water.

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METHOD OF PREPARATION OF SOLUBILISED SYSTEMS Solvent Evporation

• the drug and surfactant are dissolved in volatile organic solvents which are allowed to evaporate at room temperature

Co-solvent Evaporation

• a micellar solution is formed by adding water slowly to a solution of drug and surfactant in a water-miscible organic solvent (cosolvent) and removing the organic solvent by evaporation

Emulsion

• an oil-in-water emulsion is formed by mixing the organic solvent containing dissolved drug with an aqueous solution of the surfactant; the volatile solvent is then allowed to evaporate,

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METHOD OF PREPARATION OF SOLUBILISED SYSTEMS 

The method of preparation of the solubilised system can have a significant influence on the solubilisation capacity. Shake flask method The simplest and most commonly used method of incorporation of the drug is the so-called ‘shake flask’ method, in which excess solid drug is equilibrated with the micellar solution and unsolubilised drug subsequently removed by filtration or centrifugation.

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METHOD OF PREPARATION OF SOLUBILISED SYSTEMS Melt Loading Larger amounts of drug can often be solubilised by co-mixing the drug and surfactant at elevated temperature (typically about 60°C) and adding the resultant intimate mixture to water or buffer to form the solubilised micellar solution; this method is often referred to as ‘melt loading’. Dialysis Method In the dialysis method, drug and surfactant are dissolved in a water-miscible organic solvent followed by dialysis against water until the organic phase is replaced with water, leaving the solubilised solution.

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METHOD OF PREPARATION OF SOLUBILISED SYSTEMS Solvent Evaporation Method In the solvent evaporation method, the drug and surfactant are dissolved in volatile organic solvents which are allowed to evaporate at room temperature; the resultant dried drug/ surfactant film is then pulverised and dispersed in water. Cosolvent Evaporation Method In the cosolvent evaporation method, a micellar solution is formed by adding water slowly to a solution of drug and surfactant in a water-miscible organic solvent (cosolvent) and removing the organic solvent by evaporation. 83

METHOD OF PREPARATION OF SOLUBILISED SYSTEMS Emulsion method In the emulsion method, an oil-in-water emulsion is formed by mixing the organic solvent containing dissolved drug with an aqueous solution of the surfactant; the volatile solvent is then allowed to evaporate, leaving the solubilised micellar solution.

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PHARMACEUTICAL APPLICATIONS OF SOLUBILISATION Pharmaceutical applications of solubilisation 1. Formulation of insoluble drugs A wide range of insoluble drufgs have been formulated using the phenoenon of solublization. a. Phenolic compounds The phenolic compounds such as cresol, chlorocresol, chloroxylenol and thymol are frequently solubilized with soap to form clear solutions for use in disinfection.

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PHARMACEUTICAL APPLICATIONS OF SOLUBILISATION b. Iodophors (Solubilised solutions of iodine in non-ionic surfactant micelles) Non-ionic surfactants are efficient solubilisers of iodine, and wil incorporate up to 30% iodine by weight, of which three quarters is released as available iodine on dilution. Such iodine-surfactant system (referred to as IODOPHORS) are more stable thn idineiodide systes.they are preferref in instrument sterilization since corrosion problems are reduced. There is also evidence of an ability of iodophor solution to penetrate hair follicles of the skin, so enhancing activity. 86

PHARMACEUTICAL APPLICATIONS OF SOLUBILISATION c. Steroids The low solubility of steroids in water presents a problem in their formuation for ophthalmic use. The requirements of optical clarity preclude the use of oilly solutions or suspesions and there are many examples of the use of non_ionic surfactants as a means of producing clear solutions that are stable to steriliztaion. In most formulations, solubilization has been achieved using ploysorbates or polyethylene sorbitan esters of fatty acids.

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PHARMACEUTICAL APPLICATIONS OF SOLUBILISATION d. Essential oils. Essential oils are extensively solubilised by surfactants, polysorbates 60 and 80 being particularly well suited to this purpose. e. Water insoluble vitamins. Non-ionic surfactants are also employed in the preperation of aqueous injections of the water –insoluble vitamis A, D, E and K. polysorbate 20 and 80 being the best two solubilisers. f. Other drugs. Many other drugs have been formulated in this way, including the analgesics, sedatives, sulfonamides and antibiotics.

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PHARMACEUTICAL APPLICATIONS OF SOLUBILISATION 2. Improvement of taste. drugs of unpleasant taste can be solubilized to mask the taste e.g. multivitamin preperation. For this purpose amphipaths must be non-toxic having agreabe taste and odour. 3. Enhanced absorption solubilization leaads to enhanced absorption. It improves th eintestinal absorption of vitamin A. it also improves drug absorption from ointment bases. 4. Drug satbility Vitamin A is more resistant to auto-oxidation in aqueous non-ionic surfactants than in oils.

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PHARMACEUTICAL APPLICATIONS OF SOLUBILISATION 5. Reduce rate of hydrolysis. Solubilization can also reduce the rate of hydrolysis of many drugs.

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PHARMACEUTICAL

APPLICATIONS AND MEDICAL IMPORTACE OF

SURFAE ACTIVE AGENTS

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Reference: Physicochemical principals of pharmacy By Alexander T Forence and David Attwood



[email protected]

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