Pharmaceutics 356C
Chapter 14
Disperse Systems (Suspensions, Emulsions, Surfactants, and Aerosols)
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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 Solutions—less than 0.001 micron – Colloids—0.001 to 0.5 microns – Coarse Dispersions—greater than 0.5 microns (Much overlapping in such a classification)
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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
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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
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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 5
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
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Basis of Classification – Lyophilic (or Hydrophilic Colloid) • Solvent loving—attraction 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) (-) 7
Basis of Classification – Lyophobic (or Hydrophobic Colloid) • Low attraction to dispersion medium—must 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)
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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
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Colloid Mill
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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
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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
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Light through mist from ultrasonic nebulizer
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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 – Fick’s 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 – Stoke’s Law v = 2r2 g (ρ – ρo) / 9η – Where: v is rate of sedimentation r is radius of particle η is viscosity of dispersion medium g gravitation constant ρ is particle density ρ 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 = η 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/η (F/A) φ =1/η
(fluidity)
– Unit of viscosity – centipoise (cPs) 17
Shearing force required to produce velocity gradient between parallel plates of a block material F
A dv dx
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.
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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 = η (dv/dx) dv/dx = 1/η (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 = η (dv/dx) dv/dx = 1/η (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
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F/A = η (dv/dx) dv/dx = 1/η (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
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F/A = η (dv/dx) dv/dx = 1/η (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
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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%
100 20 2,000 4,000 100,000 4,000 13 1,400 29
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
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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
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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
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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
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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
•3. To increase chemical stability – –
Ex. Penicillin G rapid hydrolysis in solution Procaine Penicillin G no hydrolysis if decrease solubility below 1.5 mcg/ml. (G = glutamate)
•4. To Control Therapeutic Response – –
Insulin—Different Release Rate Depot Systems—Suspension Injections for time release 37
Stoke’s 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 – η = 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
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Stoke’s Law Applications • Pharmaceutically we can control suspensions by: 1.) Radius of the particles (r) V α 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
Stoke’s Law Applications • Pharmaceutically we can control suspensions by: 2.) Viscosity (η) of the medium—Suspending 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 powders—no suspending agent required, will remain suspended long enough for uniform dose • Ex: Kaolin, Mg Carbonate, Mg Oxide, Quinine sulfate and Bismuth subcarbonate—Completely insoluble
2. Indiffusable powders—suspending agent required, does not •
remain suspended long enough for patient Ex: Aspirin, sulfa drugs, sulfur in topical preps. Salicylic acid, Phenobarbital
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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
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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.
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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
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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 = γ SL ∆A
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Interfacial Properties of Suspended Particles • To approach a thermodynamically stable system: ΔF = O by:
reduce interfacial tension–Use surfactant reduce interfacial area—Control flocculation (Using Zeta Potential) --Flocculated particles: weakly bonded
--Deflocculated particles:
settle rapidly no cake re-suspend settle slowly sediment difficult to re-suspend
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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
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Caking Diagram •
Demonstrating the flocculation of a bismuth subnitrate (+ charged) suspension by means of the flocculating agent, monobasic potassium phosphate
Apparent Zeta Potential
Bismuth Subnitrate (+) Monobasic Potassium Phosphate (-)
1.0 0.5
F = Sedimentation Volume F = Vu = Final Volume of susp. Sediment Vo
Original Volume of susp
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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
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Suspending Agents • Categorize by: – Rheologic Behavior – Ionic Charge – Amount used – Internal or External – Stable pH range – Any incompatibilities
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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
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Emulsions
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Emulsions • Definition -system of 2 immiscible materials, one of which is dispersed in globular form throughout the other
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Emulsions • Terms: – Dispersed Phase—Various droplets, discontinuous phase – Continuous Phase—Carries the dispersed droplets – O/W Emulsion—Oil is the dispersed phase; water the continuous phase – W/O Emulsion—Water 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/O—Spreads more evenly on unbroken but damaged skin to protect (i.e. Water-proof sunscreen) O/W—Easily 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
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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)
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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
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Stability of Emulsions • Stability is characterized by: 1. Absence of coalescence—No 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 creaming—O/W b.) downward creaming—W/O
•
2. Coalescence and Breaking --irreversible—poor formulation; possibly increase emulsifier --physical Key is to prevent breaking—dictated 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
w
o
o
Flocculation
o
o w
Coalescence
o
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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 + Oil—Then add water [General Rule: 4:2:1 (Oil:Water:Gum)] -- Acacia + Oil, triturate, then add all water & mix -- Use ceramic M&P—More friction generated -- Requires about 3 minutes -- Can use electric mixer or blender • English (Wet Gum) Method Emulsifying Agent + Water—Then add oil (A thicker preparation—Add oil slowly) 67
Hand homogenizer High shear homogenizer 68
Examples of Official Emulsions • Castor Oil Emulsion—Laxative • Hexachlorophene Cleansing Emulsion • Mineral Oil Emulsion—Laxative • Simethicone Emulsion—Gas, 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)
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Surface Tension and Surfactants
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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 Agents—Concentrate 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)
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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
A
B
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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
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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 paraffin—IT = 57 dynes/cm (completely immiscible) – Water/ether—IT = 10.7 dynes/cm (partially miscible) – Water/alcohol—IT = 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
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Schematic of a Surface Active Agent
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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
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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 9—Lipophilic --Above 11—Hydrophilic
• 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.
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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.
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Surface Tension and CMC
• •
At CMC, surface tension does not decrease anymore ST is experimentally determined by a Du Nuoy Tensiometer
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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.
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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 children’s formulas
• To reduce irritation – Preparation of Iodophors • A solution of iodine in a surfactant (decreased irritation, odor)
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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)
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Natural Surfactants • In the GI Tract: – Bile salts • • • •
Deoxycholic Acid Chenodeoxycholic Acid Hyodeoxycholic Acid Cholic Acid
– Purpose:
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Natural Surfactants • In the lung – Mixture of phospholipids, proteins and lipids – Purpose:
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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
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Natural Surfactants • In the Eye – Cornea – Tear Interface – Aqueous Tear Film – Surface of Tear Film – Tear Film 94
