Pharmaceutics 356C

Chapter 14

Disperse Systems
(Suspensions, Emulsions, Surfactants, and Aerosols)

Disperse or Polyphase Systems

Definition: A dispersion is a system containing one or more constituents distributed throughout a homogeneous medium Can classify dispersions into three categories based on particle size
True Solutionsless than 0.001 micron Colloids0.001 to 0.5 microns Coarse Dispersionsgreater than 0.5 microns (Much overlapping in such a classification)

Disperse or Polyphase Systems

True Solutions
Molecular dispersions Particles are invisible even with the electron microscope and pass through filter paper and semi- permeable membranes

Colloidal Dispersions (Sols)

An intermediate state between true solutions and suspensions Particles cannot be seen with an ordinary microscope but can be seen with the electron microscope In addition, while the particles of a colloidal dispersion will still pass through filter paper they will not pass through semi-permeable membranes Very high surface area Particles diffuse more slowly than those of a true solution

Disperse or Polyphase Systems

Coarse Dispersions
The systems we know as emulsions or suspensions Particles (dispersed phase) are often visible with the naked eye (unaided) Will not pass through filter paper or semipermeable membranes Particles seldom diffuse Are used extensively in pharmaceutical products

Types of Colloidal Systems

There can be many types of colloidal dispersions Each phase may be a solid, liquid or gas The most important colloidal pharmaceutical preparations include:
1. Foams 2. Aerosols 3. Emulsions 4. Suspensions 5. Ointments 6. Gels 7. Magmas and Mucilages

Basis of Classification
In general colloids may be divided into three main groups This division is made on the basis of how the colloidal particles react with the dispersion medium

Basis of Classification
Lyophilic (or Hydrophilic Colloid)
Solvent lovingattraction to dispersion medium (water or alcohol) hydrophilic / alcophilic
Natural Polymers (and charge): Acacia (-), Tragacanth (-), Xanthan Gum (-), Protamines (+) Cellulose Derivatives (and charge): Methylcellulose (none), Sodium Carboxymethylcellulose (-) Synthetic Polymers (and charge): PVP (none), Carbomer (-) Particulate Colloids (and charge): Bentonite (colloidal hydrated aluminum silicate) (-), Veegum (colloidal aluminum magnesium silicate) (-)

Basis of Classification
Lyophobic (or Hydrophobic Colloid)
Low attraction to dispersion mediummust put a lot of energy into system Requires special method to manufacture
Particle size reduction or particle condensation by aggregation

Association Colloids
Amphiphilic colloids (polar and nonpolar parts of molecule) Decrease surface tension (surfactants)

Preparation of Colloids
Hydrophilic colloidal dispersions
Spontaneously disperse, no special methods

Hydrophobic colloidal dispersions

Ultrasonic generators
>20,000 Hz

Colloid mills
Less efficient; broad particle size distribution

Colloid Mill

10

Properties of Colloids
Kinetic Properties
Brownian movement
Random movement of particles in dispersion Observed by SEM Due to bombardment of small particles by molecules of dispersion medium

11

Properties of Colloids
Optical properties
Tyndall effect light scattering True solution no visible cone Colloid visible cone due to light scattering Hydrophilic colloids have less pronounced Tyndall effect than hydrophobic colloids

12

Light through mist from ultrasonic nebulizer

13

Light through colloidal dispersion of silver.

14

Properties of Colloids
Diffusion
Movement of particles from areas of high concentration to areas of low concentration to establish equilibrium Ficks First Law dQ = -DA (dc/dx) dt Amount (dQ) of substance diffusing in time (dt) across plane of area (A) is directly proportional to change in concentration (dc) with distance traveled (dx) D influenced by diffusant properties, solvent properties, temperature is not constant but depends on conditions 15

Properties of Colloids
Sedimentation
Stokes Law v = 2r2 g ( o) / 9 Where:
v is rate of sedimentation r is radius of particle is viscosity of dispersion medium g gravitation constant is particle density o is density of dispersion medium

16

Properties of Colloids
Viscosity
Measure of resistance of a liquid to flow, the more viscous the liquid the greater force required to make it flow at a particular rate Liquid composed of parallel layers or plates F/A = dv/dx
F/A is shear stress (F applied to area A) dv/dx is shear rate (velocity of shear; distance between plates Often plotted: dv/dx = 1/ (F/A)
=1/ (fluidity)

Unit of viscosity centipoise (cPs) 17

Shearing force required to produce velocity gradient between parallel plates of a block material
F dv dx A

Top plane moves at constant velocity (dv) each lower layer moves at Velocity proportional to its distance from the fixed bottom layer (dx) Result is shear of liquid. 18

Properties of Colloids - Flow

Newtonian Flow
Rate of shear linearly related shearing stress Influence of temperature Examples: Castor oil Ethyl alcohol Glycerin Olive oil Water Milk Sugar Solution Mineral Oil

19

F/A = (dv/dx) dv/dx = 1/ (F/A)

(slope = fluidity or 1 / viscosity)

20

Properties of Colloids - Flow

Non-Newtonian Flow
Plastic Flow
Apparent viscosity decreases with increasing rates of shear Van der Waals attractive forces must be overcome for flow to start Yield value material begins to flow when forces between attractive particles is overcome; is elastic before then behaves like Newtonian liquid after yield value is reached. Yield value indicates force of flocculation between particles (> degree of flocculation = higher yield value) Flocculated particles in suspension are characteristic of plastic flow

21

F/A = (dv/dx) dv/dx = 1/ (F/A)

(slope = fluidity or 1 / viscosity)

22

Properties of Colloids
Non-Newtonian Flow
Pseudoplastic Flow
Shear thinning materials No yield value Increasing rates of shear will decrease viscosity Examples are polymer dispersions (e.g. Tragacanth, Sodium Alginate, Methylcellulose, Sodium CMC) Polymers in solution, with shear stress, long chain molecules begin to align themselves in direction of flow to reduce internal resistance

23

F/A = (dv/dx) dv/dx = 1/ (F/A)

(slope = fluidity or 1 / viscosity)

24

Properties of Colloids
Non-Newtonian Flow
Dilatant
Shear thickening materials Increased resistance to flow as the shear rate is increased with agitation Examples include dispersions with >50% solids of small deflocculated particles, pastes

25

F/A = (dv/dx) dv/dx = 1/ (F/A)

(slope = fluidity or 1 / viscosity)

26

Properties of Colloids
Thixotropy
Isothermal and slow recovery, on standing, of a consistency lost through shearing Asymetric particles form loose 3-dimensional structure that when lost takes time to reform Hysteresis loop measure of thixotropic breakdown, the larger the hysteresis loop the more thixotropic the liquid is. Useful property to formulate liquids to control settling Examples include Bentonite Magma

27

28

Approximate Viscosities of Gels at RT (mPa s or cPs)

Acacia Alginic acid Guar gum HPMC E4 HPMC K100 MC A4 Starch Xanthan gum 30% 0.5% 1% 2% 2% 2% 2% 1%
29

100 20 2,000 4,000 100,000 4,000 13 1,400

Properties of Colloids
Electrical Properties of Colloids
Zeta potential governs degree of repulsion or attraction between adjacent like charged dispersed particles Difference in potential between the surface of a tightly bound layer and the electroneutral region of the solution Hydrophobic colloids have critical zeta potential
above critical zeta potential repulsive forces > attractive forces below critical zeta potential attractive forces > repulsive forces (controlled flocculation)

Manipulate zeta potential

Oppositely charged electrolytes to lower zeta potential Add another colloid with opposite charge to lower zeta potential

Zeta potential gives indication of stability of a colloidal system WE WANT: controlled flocculation or reduction of repulsion in order to stabilize dispersion

30

31

32

Properties of Colloids
Protective Colloids
Hydrophobic colloids are difficult to stabilize due to large surface area and large free surface energy, particles will flocculate to reduce energy Coat hydrophobic colloid with hydrophillic colloid to stabilize Examples include gelatin, acacia, albumin, tragacanth, methylcellulose, Na oleate

33

Suspensions

34

Suspension
Definition -A heterogeneous system in which the continuous phase is a liquid or semisolid, and the dispersed phase consists of a dispersed solid Acceptable properties of a suspension:
1. Particles should not settle rapidly 2. When particles settle, should not form hard cake (i.e. be readily dispersible) 3. Product should be viscous enough so patient gets uniform dose, but not so viscous to prevent pouring or injecting

35

Pharmaceutical Suspensions
Heterodisperse systems Particles often > 1 um (usually > 10 um) Complex continuous phase
Viscosity Inducing agents, flavors, etc.

Particle shapes non-spherical High solids content

36

Why Use Suspensions?

1. No suitable solvent available to dissolve drug (i.e. ZnO) 2. Mask unpleasant taste of drugs
(i.e. chloramphenicol palmitate, Chloromycetin, Parke-Davis ) garlic-like taste for chloramphenicol palmitate salt masks taste , also more stable in gastric juices so increased blood levels at pH 3-6, palmitate hydrolyzes Ex. Penicillin G rapid hydrolysis in solution Procaine Penicillin G no hydrolysis if decrease solubility below 1.5 mcg/ml. (G = glutamate) InsulinDifferent Release Rate Depot SystemsSuspension Injections for time release

3. To increase chemical stability

4. To Control Therapeutic Response

37

Stokes Law
Most important law controlling formulation of suspensions In equation:
V = rate of settling of the particles r = radius of the particles p = density of the particles po= density of the medium g = gravity constant = viscosity of the dispersion Stokes Law assumes:
Particles are spherical Suspensions are dilute (<2% w/v) Particles do not flocculate No Brownian movement No electrical effects

38

Stokes Law Applications

Pharmaceutically we can control suspensions by:
1.) Radius of the particles (r)
V r2 (Decrease radius, then increase SA and increase surface energy) -a high surface energy leads to aggregate formation, so use a peptizing agent (Na+ citrate in calamine lotion) to place surface charge on the particles so they do not aggregate, and the surface charge repels the particles - aggregates form to reduce (minimize) surface energy.

39

Stokes Law Applications

Pharmaceutically we can control suspensions by:
2.) Viscosity () of the mediumSuspending Agents
--Rate of settling is inversely proportional to viscosity Examples of suspending agents: -acacia, tragacanth In, too sticky for Ex -Carboxymethylcellulose (CMC) In or Ex -Veegum (montmorrilonite clays) -use hydrated, In or Ex -Carbopol -a gum, use in pH range 5-10, In or Ex --Viscosity inducing agents -swell in water to increase viscosity

40

Methods of Preparation of Suspensions

A. Dispersion Method -add dispersion medium to finely
divided particles 1. Diffusible powdersno suspending agent required, will
remain suspended long enough for uniform dose Ex: Kaolin, Mg Carbonate, Mg Oxide, Quinine sulfate and Bismuth subcarbonateCompletely insoluble

2. Indiffusable powderssuspending agent required, does not

remain suspended long enough for patient Ex: Aspirin, sulfa drugs, sulfur in topical preps. Salicylic acid, Phenobarbital

41

General Method of Preparation

1. Material must be finely divided 2. Add small amount of vehicle to make smooth, lump free paste. 3. Slowly dilute with remainder of vehicle with constant stirring (3/4 volume of prep.) in mortar 4. Add, through gauze, to pre-calibrated bottle, rinse mortar with remainder of vehicle into cylinder 5. qs to volume with rinse in cylinder NOTE: If suspension is thick, use calibrated bottle to qs with NOTE: With soluble solids, add as solution AFTER forming initial dispersion (same with tinctures). If add before, aggregates will form

42

Fritsch Planetary Micro Mill For reducing particle size down To colloidal size range, dry or in suspension. For mixing and homogenizing of emulsions, suspensions, pastes. Uses grinding balls for high impact energy.

43

Methods of Preparation of Suspensions

1. Chemical interaction (Lotio Alba, White Lotion) sulfurated potash + zinc sulfate ("stink") + ("zinc") K2S + ZnSO4 K2SO4 + ZnS

prepare as separate solutions, filter, add "stink" to the "zinc" slowly with stirring, obtain fine, white ppt (zinc polysulfides) used as astringent (acne) 2. Alteration

of solvent

44

Interfacial Properties of Suspended Particles

Thermodynamically unstable: --Flocculate--light, fluffy conglomerates held by weak Van der Waals forces --Aggregates--caking stronger forces to form solid aggregate (Trying to overcome free surface energy in suspension) F = SL A

45

Interfacial Properties of Suspended Particles

To approach a thermodynamically stable system:
F = O by: reduce interfacial tensionUse surfactant reduce interfacial areaControl flocculation (Using Zeta Potential) --Flocculated particles: weakly bonded
settle rapidly no cake re-suspend settle slowly sediment difficult to re-suspend

--Deflocculated particles:

46

Sedimentation Volumes
Sedimentation volumes produced by adding varying amounts of flocculating agent Examples b and c are pharmaceutically acceptable Bismuth Subnitrate (+) Monobasic Potassium Phosphate (-)

F = Sedimentation Volume F = Vu = Final Volume of Susp. Sediment Vo Original Volume of Susp

47

Caking Diagram
Bismuth Subnitrate (+) Monobasic Potassium Phosphate (-)

Demonstrating the flocculation of a bismuth subnitrate (+ charged) suspension by means of the flocculating agent, monobasic potassium phosphate
F = Sedimentation Volume F = Vu = Final Volume of susp. Sediment Vo Original Volume of susp

Apparent Zeta Potential

1.0 0.5

48

Examples of Official Suspensions

1. Chloramphenicol Palmitate Oral Suspension USP
(Chloromycetin Palmitate Suspension, ParkeDavis) -Derivative increases stability and masks taste -palmitate deriv. is hydrolyzed off in GI tract and chloramphenicol is absorbed. -for eye and ear drops, derivative not necessary because acid stability or taste are not problems USE: against gm (-) and gm (+) bacteria Caution -blood dyscrasias (bone marrow depression) 49

Examples of Official Suspensions

B. EXTERNAL SUSPENSIONS:
1. Calamine Lotion USP
8% ZnO + 8% Calamine (calamine consists of 98% ZnO + 2% Fe203) -powders are levigated with glycerin, then paste is diluted with Bentonite Magma + calcium hydroxide USE: protectant, relieves itching, sunburn pain, poison ivy

2. Phenolated Calamine Lotion USP

Calamine Lotion USP + 1% Phenol 3. White Lotion NF -see previous notes -must add stink" to the "zinc" in order to obtain fine particles as the precipitate

50

Suspending Agents
Categorize by:
Rheologic Behavior Ionic Charge Amount used Internal or External Stable pH range Any incompatibilities

51

Examples of Suspending Agents

Gums and Derivatives
Acacia Tragacanth Pectin Carbopol

Clays
Bentonite Veegum
52

Examples of Suspending Agents

Cellulose Derivatives
Methylcellulose Carboxymethyl Cellulose Sodium HPMC HPC

53

Emulsions

54

Emulsions
Definition -system of 2 immiscible materials, one of which is dispersed in globular form throughout the other

55

Emulsions
Terms:
Dispersed PhaseVarious droplets, discontinuous phase Continuous PhaseCarries the dispersed droplets O/W EmulsionOil is the dispersed phase; water the continuous phase W/O EmulsionWater is the dispersed phase; oil is the continuous phase
56

Why Use Emulsions?

1. Permits administration of liquid drug in form of tiny globules rather than in bulk 2. 0/W emulsion if oil tastes offensive 3. Irritating medicinal agents to be applied externally onto the skin (i.e. lotion or cream)keep in friendly environment 4. 0/W vs. W/0 for topical preparations W/OSpreads more evenly on unbroken but damaged skin to protect (i.e. Water-proof sunscreen) O/WEasily removed from skin 57

To Maintain a Stable Emulsion

1. Reduce interfacial tension between the 2 immiscible liquids by using SAA (wetting agent) 2. Emulsifying agent must be amphiphilic (SAA) 3. There must be a high interaction energy between the non-polar portions. These London attractive forces increase the tensile strength of the film, making it more difficult to break (tough and pliable) --SAA forms a film at interface a. prevents coalescence of the droplets of oil b. stabilizes the emulsion 58

London dispersion forces

Nonpolar tail

Interface

Polar head

59

Emulsions for Internal Use

Use O/W type Acacia is best emulsifying agent for internal use Desirable properties of an emulsifying agent (Amphiphilic)
Non-toxic (GRAS listed) NO therapeutic activity Amphiphilic structure High HLB value (i.e. 8 to 18)

60

Emulsions for External Use

O/W or W/O types Use soaps as the emulsifying agents
Monovalent soaps
Na+ and K+ Water soluble; Forms O/W

Divalent soaps Ca++ soaps or long chain fatty acids

Water insoluble; Forms W/O

61

Stability of Emulsions
Stability is characterized by:
1. Absence of coalescenceNo forming of one droplet from two droplets 2. Absence of creaming (Phase separation) 3. Nice color 4. Pleasant odor 5. Esthetic appearance
62

Stability of Emulsions
1. Flocculation and Creaming (Measure of Stability)
- flocculation and concentration of globules - reversible shake or agitate - related by Stoke's Law Density difference, viscosity important a.) upward creamingO/W b.) downward creamingW/O

2. Coalescence and Breaking --irreversiblepoor formulation; possibly increase emulsifier

--physical Key is to prevent breakingdictated by proper choice and level of emulsifying agent(s)

3. Phase Inversion
--must be controlled often results in finer dispersed phase --O/W to W/O (Internal Phase becomes External Phase)

63

Stability of Emulsions
Na Stearate (o/w) + CaCl2

Ca Stearate (w/o)

What is the emulsifying agent?

64

Flocculation

o w Coalescence

65

Preservation of Emulsions
Growth of microorganisms cause: --Physical phase separation Partitioning --Discoloration Turns white or brown --Gas emission (possibly) --Odor formation --Changes in rheological properties Microorganisms degrade the emulsifying agent Use Preservatives -- Essential --i.e. Methylparaben and Propylparaben 66

Emulsion Technology
Industrial Homogenizers
--In pharmacy practice, use mortar & pestle

Continental (Dry Gum) Method Emulsifying agent + OilThen add water [General Rule: 4:2:1 (Oil:Water:Gum)] -- Acacia + Oil, triturate, then add all water & mix -- Use ceramic M&PMore friction generated -- Requires about 3 minutes -- Can use electric mixer or blender English (Wet Gum) Method Emulsifying Agent + WaterThen add oil (A thicker preparationAdd oil slowly) 67

Hand homogenizer High shear homogenizer

68

Examples of Official Emulsions

Castor Oil EmulsionLaxative Hexachlorophene Cleansing Emulsion Mineral Oil EmulsionLaxative Simethicone EmulsionGas, Flatulence
69

Other Emulsifying Agents

Anionic
Alkali Soaps (RCOO- + monovalent) Metallic Soaps ((RCOO)2 + di or tri valent) Soaps of Organic Amines Sulfated Compounds (R-OSO3Na) Sulfonates (R-SO3Na)

Cationic
Quaternary ammonium compounds
70

Other Emulsifying Agents

Non-Ionic (generally esters

R-COOR1)

Polyethylene glycol 400 monostearate Sorbitan monopalmitate (Span 40) Sorbitan monooleate (Span 80) Polyoxyethylene sorbitan monooleate (Tween 80) Polyoxyethylene sorbitan monolaurate (Tween 20) Silicones:
Low MW; have surfactant properties High MW; have antifoaming action

Natural and Modified Natural

Alginates Cellulose derivatives Gums (Acacia, Tragacanth, Pectin) Lipids (Lecithin)

71

Surface Tension and Surfactants

72

Surface Tension
Surface Tension is the
inward force or stress or tension that tends to pull molecules into the liquid. force per unit area at the surface of the liquid which opposes expansion of the surface (dyne/cm or erg).

Surface Tension is the term used when we have an interface of a liquid or solid with air Surface Active AgentsConcentrate at the surface and reduce the ST of the liquid
(Note: Electrolytes (NaCl, KCl) tend to concentrate in the bulk of the medium and cause an increase in ST)

73

Surface Tension Example

Surface tension and interfacial tension are important considerations in pharmaceutical technology. Consider a beaker of liquid as being a beaker-full of molecules. Molecules at the surface behave differently than those in the interior of the liquid. Molecule A in the interior is completely surrounded by identical molecules. These molecules are oriented in such a way that there are no residual forces. Molecules surrounding A exert equal forces in all direction and there is no tendency for molecules to be pulled one way or the other With molecule B at the surface, the situation is different. The molecules in the interior of the liquid tend to pull B into the interior

74

Surface Active Agents - Basic Characteristics

Amphiphilic Molecules
Contain polar and non-polar portions Are oriented at the surface and significantly effect ST Are not completely hydrophobic or hydrophilic Soluble in water and in oil Must be a balance between the polar and nonpolar moieties for the molecule to be an effective SAA 75

Sodium Lauryl Sulfate

76

Interfacial Tension
Definition: The force per unit length at the interface between 2 immiscible liquids (Usually an emulsion in pharmacy) Force measured with the Du Nuoy Tensiometer (dynes/cm) An INTERFACE is a boundary between two phases I.T.Determines miscibility of liquids Examples:
Water/liquid paraffinIT = 57 dynes/cm (completely immiscible) Water/etherIT = 10.7 dynes/cm (partially miscible) Water/alcoholIT = 0 dynes/cm (completely miscible) THUS: To improve miscibility of systems, we must lower the I.T. HOW? Use Surface Active Agents (Surfactants)

77

Surfactants at the interface

78

Schematic of a Surface Active Agent

79

Properties of Surfactants
Surfactants may be described variously by a number of different titles depending upon how they are used 1. Detergents 2. Wetting Agents 3. Solubilizers 4. Emulgents See Examples of Surfactants Given Earlier 80

The HLB System

Developed for and is important in surfactant selection for emulsions, etc.
The Hydrophilic-Lipophilic Balance System (HLB) System is based on the knowledge that all surfactants combine both lipophilic and hydrophilic groups in the molecule The proportion of the weight percentages of these two portions will determine the physical behavior of the surfactant. Particularly applies to non-ionic surfactants The ratio determines their relative oil-soluble and water-soluble tendencies The balance between these two tendencies is the HydrophilicLipophilic Balance. Indicates the relative size and strength of the two portions of the molecule In the HLB system each surfactant is assigned a numerical value which is known as its HLB

81

HLB System
In general:
--Empirical Scale(1-20 or 1-30) to describe the properties of non-ionic surfactants --Below 9Lipophilic --Above 11Hydrophilic

Function:
HLB 1 -3 4 -6 7 -9 8 -18 13 -15 10- 18 Antifoaming W/O emulgent Wetting agent O/W emulgent Detergent Solubilizer

82

Solubilization
The ability of surfactants to increase the solubility of substances which normally only have limited solubility in the dispersion medium Surfactants are usually non-ionic and dispersion medium is water Known as micellar solubilization Used to bring into aqueous dispersion a wide range of substances which are normally considered to be water insoluble Mechanism of Solubilization Non-ionic surfactants act as solubilizing agents because of their ability to form micelles Micelles are also formed by ionic surfactants as well but these are less extensively used in solubilization (pharmaceutically) We showed earlier that when we add a surfactant to water it forms a monomolecular layer on the surface of the water That is, it concentrates at the interface because it is surface-active

83

Mechanism of Solubilization, cont.

Once the surface of the water has been covered by this monomolecular film the bulk of the solution then becomes saturated with the surfactant. When saturation has been achieved the surfactant which up to this time has been in the monolayer form begins to form molecular aggregates. That is, as the concentration of the surfactant is increased the surface becomes covered, then, the solution becomes saturated and finally molecular aggregates begin to form. These colloidal aggregates are known as micelles. The molecules making up the micelles may be arranged in either a spherical or in a laminar or palisade form. All micelles have a hydrophobic core and hydrophilic exterior. Micelles are separate and distinct entities from the dispersion medium.

84

Schematic of Micelle
Surfactant placed in water, hydrophilic heads orient to outer water phase and long chain hydrophobic tails orient together.

85

Critical Micelle Concentration

Definition: The concentration of the surfactant at which the micelles begin to form The CMC is usually characterized by a distinct change in the physical properties of the solution. For example 1. Surface tension 2. Conductivity 3. Osmotic pressure Have a change in these parameters as a function of concentration. A surfactant or surface active agent will concentrate at the surface of liquid and reduce the surface tension of the liquid. As the concentration of SAA is increased there is a steady reduction in S. T. until the CMC is reached (See illustration). At this point with further increases in concentration there is no further reduction in surface tension. THUS, the point of lowest surface tension is the CMC. When no more molecules of surfactant can align themselves on the surface there is no further reduction in surface tension. Further addition of surfactant will result in the formation of micelles.

86

Surface Tension and CMC

At CMC, surface tension does not decrease anymore ST is experimentally determined by a Du Nuoy Tensiometer

87

Solubilization
SOLUBILIZATION
Since the micelle core is essentially a paraffin-like region it is capable of dissolving oil-soluble substances. The process of dissolving water-insoluble substances into solution by incorporating them into micelles is known as solubilization.

88

Applications of Solubilization
To improve chemical stability
Vitamin A less readily oxidized in the solubilized form The polar or hydrophilic head of the micelle provides protection by preventing the OH- ion which catalyzes oxidation or hydrolysis from reaching the chemical to be protected

To improve drug absorption

Improvement orally and through the skin

To improve solubility
Vitamin A and D can be solubilized to give a waterdispersible mixture that can be added to childrens formulas

To reduce irritation
Preparation of Iodophors
A solution of iodine in a surfactant (decreased irritation, odor) 89

Wetting Agent
A surfactant that when dissolved in water, lowers the advancing contact angle and aids in displacing air from surface with liquid phase. (complete wetting vs. insufficient wetting)

90

Natural Surfactants
In the GI Tract:
Bile salts
Deoxycholic Acid Chenodeoxycholic Acid Hyodeoxycholic Acid Cholic Acid

Purpose:

91

Natural Surfactants
In the lung
Mixture of phospholipids, proteins and lipids Purpose:

92

Exosurf Neonatal is a protein-free synthetic lung surfactant that dramatically reduces mortality and morbidity in premature infants suffering from, or at risk of, Respiratory Distress Syndrome (RDS) due to surfactant deficiency. Exosurf Neonatal is effective in the treatment of premature infants suffering from or at the risk of, Respiratory Distress Syndrome (RDS) due to surfactant deficiency. (GSK)

Each 10mL vial contains: DPPC 108mg Cetyl Alcohol 12mg Tyloxopol 8mg NaCl 47mg HCl/NaOH to adjust pH Reconstitute with 8mL SWFI pH = 5-7 Osm = 185 mOsm/L

93

Natural Surfactants
In the Eye
Cornea Tear Interface Aqueous Tear Film Surface of Tear Film Tear Film
94