Podcast
Questions and Answers
Which of the following are examples of multi-phase systems?
Which of the following are examples of multi-phase systems?
What is the main characteristic of dispersed systems?
What is the main characteristic of dispersed systems?
They consist of solid particulate matter distributed throughout a continuous phase.
Dispersed systems generally have a clear appearance.
Dispersed systems generally have a clear appearance.
False
What does the contact angle (θ) indicate?
What does the contact angle (θ) indicate?
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What properties are associated with non-Newtonian fluids?
What properties are associated with non-Newtonian fluids?
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Name a type of agent that facilitates the dispersion of two immiscible liquids.
Name a type of agent that facilitates the dispersion of two immiscible liquids.
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Emulsions are thermodynamically stable.
Emulsions are thermodynamically stable.
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The layer of air existing on the surface of dry powders can be displaced by a ______.
The layer of air existing on the surface of dry powders can be displaced by a ______.
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Match the following agents with their functions:
Match the following agents with their functions:
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Which type of emulsion involves oil dispersed in water?
Which type of emulsion involves oil dispersed in water?
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What type of emulsifier is used to form O/W emulsions?
What type of emulsifier is used to form O/W emulsions?
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Which of the following is an example of a cationic surfactant?
Which of the following is an example of a cationic surfactant?
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What is the purpose of surfactants in emulsions?
What is the purpose of surfactants in emulsions?
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Natural surfactants are widely used in products needing a long shelf-life.
Natural surfactants are widely used in products needing a long shelf-life.
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Bile salts are synthesized in the ______ and secreted into the gut.
Bile salts are synthesized in the ______ and secreted into the gut.
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What is the HLB value range that indicates a surfactant suitable for O/W emulsifying agents?
What is the HLB value range that indicates a surfactant suitable for O/W emulsifying agents?
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Name a semi-synthetic hydrophilic colloid.
Name a semi-synthetic hydrophilic colloid.
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Match the emulsifiers to their examples:
Match the emulsifiers to their examples:
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Surfactants are useful for increasing the ______ of poorly soluble drugs.
Surfactants are useful for increasing the ______ of poorly soluble drugs.
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What are Tweens and Spans?
What are Tweens and Spans?
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What is the required HLB in the provided calculation?
What is the required HLB in the provided calculation?
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What is the HLB of Tween 80?
What is the HLB of Tween 80?
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What is the HLB of Span 80?
What is the HLB of Span 80?
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What is the required HLB for O/W emulsion preparation?
What is the required HLB for O/W emulsion preparation?
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What is the HLB of Tween 40?
What is the HLB of Tween 40?
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What is the HLB of Span 60?
What is the HLB of Span 60?
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The primary emulsion is prepared using a ratio of ___ parts fixed oil, ___ parts water, and ___ part emulsifier.
The primary emulsion is prepared using a ratio of ___ parts fixed oil, ___ parts water, and ___ part emulsifier.
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Which emulsification method involves dispersing acacia in the oil before adding water?
Which emulsification method involves dispersing acacia in the oil before adding water?
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What are the suitable methods for emulsification using surfactants?
What are the suitable methods for emulsification using surfactants?
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What is the risk of adding acid to in situ soap emulsions?
What is the risk of adding acid to in situ soap emulsions?
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What is the degree of flocculation defined as?
What is the degree of flocculation defined as?
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O/W emulsions can be diluted with water.
O/W emulsions can be diluted with water.
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What is Stokes' Law used to express?
What is Stokes' Law used to express?
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W/O emulsions are able to conduct electricity.
W/O emulsions are able to conduct electricity.
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What happens during coalescence in emulsion instability?
What happens during coalescence in emulsion instability?
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Which factors affect the velocity of sedimentation according to Stokes' Law?
Which factors affect the velocity of sedimentation according to Stokes' Law?
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Larger particles fall more slowly in a fluid.
Larger particles fall more slowly in a fluid.
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What is that ratio of sedimentation volume (F) for an ideal suspension?
What is that ratio of sedimentation volume (F) for an ideal suspension?
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What is one way to achieve controlled settling in suspensions?
What is one way to achieve controlled settling in suspensions?
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Which of the following emulsions are suitable for intravenous use?
Which of the following emulsions are suitable for intravenous use?
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What is the function of the emulsifier in emulsions?
What is the function of the emulsifier in emulsions?
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Which of the following typically increases the difficulty of redistributing a suspension after sedimentation?
Which of the following typically increases the difficulty of redistributing a suspension after sedimentation?
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The term used to describe the slow release of a drug over an extended period of time is called ____ Release.
The term used to describe the slow release of a drug over an extended period of time is called ____ Release.
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Give an example of a commonly used preservative for O/W emulsions.
Give an example of a commonly used preservative for O/W emulsions.
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What are the components of oral suspension dosage forms?
What are the components of oral suspension dosage forms?
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Density is the measure of how much mass occupies a certain volume.
Density is the measure of how much mass occupies a certain volume.
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What kind of labels are required for suspensions?
What kind of labels are required for suspensions?
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What effect does syneresis have on gels?
What effect does syneresis have on gels?
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Which type of gel consists of small, discrete particles?
Which type of gel consists of small, discrete particles?
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Study Notes
Multi-Phase (Dispersed) Systems
- Consists of particulate matter dispersed throughout a continuous phase.
- Common examples: suspensions, emulsions, gels, magmas.
- Their properties are influenced by the interface between two phases.
Dispersed Systems
- Preparations with solid particulate matter distributed in a dispersion medium.
- Heterogeneous systems.
- Requires shaking well for proper distribution.
- Typically opaque in appearance.
- Increased viscosity compared to solutions.
- Exhibits non-Newtonian flow, where viscosity changes with applied force.
Advantages of Dispersed Systems
- Easy to swallow, flexible dosing, easy administration.
- Rapid onset of action, often faster than solid dosage forms.
- Allows for modified onset of action, like extended or delayed release.
Disadvantages of Dispersed Systems
- Non-homogeneous nature.
- Tendency to separate, requiring a "Shake Well" label.
- Bulkier compared to solid dosage forms.
- Potential taste issues.
- Certain drugs are not stable in liquid forms.
- Concerns about dose accuracy, spills, and improper measuring devices.
Additional Excipients in Multi-Phase Liquids
-
Emulsifying agents: Facilitate and stabilize dispersion of two immiscible liquids.
- Examples: Polysorbate (Tween) 80, Span 80, Acacia.
-
Encapsulating or solubilizing agents: Promote and maintain dispersion of finely subdivided droplets of liquid in an immiscible vehicle.
- Examples: Acacia, Cetomacrogol, Cetyl alcohol, Glyceryl monostearate, Sorbitan monooleate.
Surfactant
- Substances that adsorb onto interfaces between phases to reduce interfacial tension.
- Examples: Benzalkonium chloride, Polysorbate 80, Sodium lauryl sulfate.
Levigating Agent
- Intervening liquid to reduce the particle size of a powder by grinding, typically in a mortar.
- Used for complete wetting and even dispersion of solid ingredients in a liquid or semisolid product.
- Displaces the air film on dry powder surfaces.
- Examples: Mineral oil, Glycerin, Propylene glycol.
Suspending Agent
- Viscosity-increasing agent to reduce sedimentation rate of particles in a vehicle where they are insoluble.
- Examples: Bentonite, Carbomers (Carbopol®), Cellulose derivatives (MC, HEC, HPMC, HPC), Tragacanth, Polyvinyl alcohol.
Wetting of Solid Particles
- Crucial for suspensions.
- Some solids float on water or other liquids, like talc or charcoal.
- Wetting refers to the ability of a liquid to displace air and spread over a solid's surface.
- Particles need to be wetted for immersion in the liquid, requiring the liquid to displace air and spread over the surface.
Wetting of Solid Particles: Contact Angle (θ)
- Describes how well solids are wetted.
- Depends on the nature of the liquid and the solid surface (hydrophilic vs hydrophobic).
Wetting of Solid Particles: Contact Angle and Wettability
- Complete wetting: Contact angle is 0º.
- Readily wetted solids: 0º < contact angle < 90º.
- Poorly wetted solids: 90º < contact angle < 180º.
- Non-wetted: Contact angle is 180º.
Problems with Insufficient Wetting
- Inability to mix powders with liquids to form suspensions.
- Incomplete absorption of tablet/capsule ingredients by GI fluids due to lack of wetting, causing dissolution problems.
- Wetting agents can increase interfacial contact to address this issue.
Particle Aggregation/Caking
- Particle aggregation: Small particles attract each other, forming larger, heavier particles that fall out of suspension but can be resuspended.
- Caking: Formation of a solid mass at the bottom of the bottle, where agglomerated particles are difficult to resuspend.
- Prevention: Development of surface charge through:
- Ionization of surface groups: Carboxylic acid groups, amines.
- Adsorption of electrolytes from the solution onto particle surface.
- Adsorption of charged surfactant molecules from the solution.
Zeta (ζ) Potential
- Also known as electrokinetic potential.
- Controls the degree of repulsion between similarly charged, dispersed particles.
- Higher zeta potential = More stable suspension.
- Below a threshold value, attractive forces exceed repulsive forces, leading to particle aggregation and instability.
Interfacial Phenomena
- Surface: Boundary between two phases, where one is strictly gas, like air.
- Interface: Boundary between two immiscible phases. Every surface is also an interface.
-
Surface Tension:
- Describes the interface between liquids and gas.
- Due to unbalanced molecular cohesive forces near the surface, creating a net attractive force towards the bulk of the liquid.
- The surface tends to contract and resemble a stretched elastic membrane.
Surface Tension
- Demonstrates the forces present at a liquid/gas interface.
Interfacial Tension
- Force of attraction between molecules at the interface of two fluids.
- For air/liquid interfaces, it's called surface tension.
- Higher interfacial tension indicates a tendency for the two liquids to separate into distinct phases.
Factors Affecting Interfacial Tension
- Temperature: Reduced interfacial tension as temperature increases.
- The addition of certain solutes, like surfactants, reduces surface tension.
Interfacial Tension (γs) and Energy
- Correlates with the energy required to increase the contact area between two immiscible liquids.
- ΔE = γs ΔA, meaning more energy is needed to increase the contact area, which can be achieved through:
- Adding heat.
- Vigorous stirring.
- Decreasing interfacial tension by adding surfactants.
Emulsions
- A dispersion where the dispersed phase comprises small globules of liquid distributed in an immiscible vehicle.
- Dispersed phase = Internal phase, discontinuous phase.
- Dispersion medium = External phase, continuous phase.
- Thermodynamically unstable, requiring an emulsifying agent for stability.
- Suitable for topical, oral, and parenteral delivery.
Emulsion Types
- Oil-in-Water (O/W): Oil dispersed in water. Oil is the internal phase.
- Water-in-Oil (W/O): Water dispersed in oil. Water is the internal phase.
Emulsion Stability
- Contact area between water and oil is very large, demanding significant energy for increasing surface area, making the system unstable.
- Cohesive forces among similar molecules (water with water, oil with oil) drive them to separate.
Emulsifier Role
- Emulsifiers stabilize emulsions by forming a film around dispersed droplets, preventing coalescence.
Factors Affecting Emulsion Type
- Emulsifier: Some emulsifiers can form either type of emulsion, while others are specific to O/W or W/O.
- Phase-Volume Ratio: Generally, the larger volume liquid forms the external phase.
- Order of Mixing: Can have some influence on emulsion type.
Purpose of Emulsions and Emulsification
- To achieve stable, homogeneous mixtures of immiscible liquids.
- Palatable delivery of distasteful oils (O/W).
- Topical applications (O/W or W/O).
- Administering irritating medications topically as the internal phase.
- Uniform mixing of oil-soluble agents (W/O).
- Oral and IV emulsions are typically O/W, while topical emulsions are W/O or O/W.
Features of a "Good" Emulsion
- Stable: Maintains homogeneity and integrity over time.
- Even Consistency: Uniform texture throughout the emulsion.
- Proper Viscosity: Easy to remove and use, like pourable lotions or easily dispensed creams.
- Small Droplet Size: Smaller droplet size enhances stability and aesthetic appearance.
- Slow Droplet Aggregation: Droplets should aggregate slowly and be readily re-dispersed after shaking.
Rheology of Emulsions
- Rheology: Study of deformation and flow of matter.
- Factors affecting rheology:
- Continuous phase viscosity.
- Phase-volume ratio.
- Emulsifier.
- Droplet size and distribution.
- Emulsions generally exhibit non-Newtonian rheology, where viscosity changes with applied force.
Preparation of Emulsions
- Depends on the desired emulsion type and the emulsifier used.
- Three types of emulsifiers:
- Hydrophilic colloids
- Finely divided solid particles
- Surfactants
Expected Qualities of an Emulsifier
- Compatible: Non-interfering with product stability and efficacy.
- Stable: Does not deteriorate within the preparation.
- Non-toxic: Safe for intended use.
- Minimal Color, Odor, Taste: Does not significantly affect the product's sensory properties.
- Effective Emulsification: Forms and maintains the desired emulsion type for the product's shelf life.
1) Hydrophilic Colloids
- Water-soluble polymers that typically form O/W emulsions.
- Form multi-molecular films around dispersed oil droplets.
- Do not significantly lower surface tension.
- Increase the viscosity of the dispersion medium.
- Less common in pharmaceuticals, but still frequently used in the food industry.
Examples of Hydrophilic Colloids
- Natural (carbohydrate-based): Acacia, tragacanth, alginates, pectin, agar, carageenan.
- Natural (protein-based): Casein, gelatin.
- Semi-synthetic: Methylcellulose, sodium carboxymethylcellulose.
- Synthetic: Carbopol (derivative of acrylic acid).
2) Finely Divided Solids
- Adsorb at the interface between immiscible liquids.
- Form a film of solid particles around dispersed globules.
- O/W emulsions are typically formed by powders preferentially wetted by water.
- W/O emulsions are formed by powders preferentially wetted by oil.
- Examples:
- Bentonite (O/W and W/O for external use).
- Magnesium hydroxide (O/W for internal use).
- Bentonite consists mostly of crystalline clay minerals, which are hydrated aluminum silicates containing iron, magnesium, sodium, or calcium.
3) Surfactants
- Surface active agents, detailed discussion in upcoming slides.
Surfactants
- Surfactants are adsorbed at oil-water interfaces, forming monomolecular films that reduce interfacial tension.
- This prevents coalescence of dispersed droplets, promoting emulsion stability.
- Ideal films are flexible and may exhibit surface charge effects.
- Combinations of emulsifiers are commonly used, with a hydrophilic agent in the aqueous phase and a hydrophobic agent in the oil phase.
- The type of emulsion (O/W or W/O) depends on the properties of the emulsifier, specifically its Hydrophilic-Lipophilic Balance (HLB).
- Surfactants with HLB 4-6 produce W/O emulsions, while those with HLB 8-18 create O/W emulsions.
- Examples include Tweens and Spans, both fatty acid esters of sorbitan derivatives.
Surfactants: Properties
- Molecules with both hydrophobic and hydrophilic components, allowing them to adsorb at interfaces.
- Decrease interfacial tension by orienting at the interface, separating immiscible phases.
- Hydrophilic portion remains in the aqueous phase, while the hydrophobic portion stays in the non-aqueous phase.
- At high enough concentrations, surfactants can form micelles.
Four Main Classes of Surfactants
- Anionic Surfactants: Possess a negative charge in their hydrophilic portion, electrolytes, commonly used in detergents, shampoos, body cleansers. Inexpensive, but oral toxicity limits them to topical use. Examples include soaps (sodium salts of fatty acids) and sodium lauryl sulfate.
- Cationic Surfactants: The cation provides emulsifying properties, electrolytes, exhibit disinfectant and preservative properties. Oral toxicity limits them mainly to topical and ophthalmic use. Incompatible with anionic surfactants, often used in combination with non-ionic surfactants. Example: Benzalkonium chlorides.
- Amphoteric Surfactants: Possess both positive and negative charges in their hydrophilic portion, adaptable to different pH values. Rarely used as the only surfactant. Example: Sodium lauroylsarcosinate.
- Non-ionic Surfactants: Their hydrophilic portion lacks a charge and they are non-electrolytes. Examples include Tweens, Spans, and Cremophores.
Naturally Occurring Surfactants
- Derived from plant and animal sources, however, they exhibit considerable batch-to-batch variability and susceptibility to microbial growth, limiting their use in long shelf-life products.
- Still commonly used in compounding. Examples include beeswax, wool fat (lanolin), wool alcohols, acacia and other plant gums.
Naturally Occurring Surfactants: Key Roles
- Bile salts: Synthesized in the liver and secreted into the gut for digestion of fats. Highly surface active, play a crucial role in the digestion and absorption of fats. Increase dissolution rate of poorly water-soluble drugs, improving their absorption and bioavailability.
- Phospholipids: Building blocks for biological membranes. Found in the alveolar lining of lungs, contributing to surface tension regulation and preventing collapse of air sacs. Deficiency in newborns leads to respiratory distress syndrome. Artificial or animal-derived surfactants can be administered to infants via endotracheal tube.
- Phospholipids in the tear film: Contribute to tear film spreading over the cornea, reducing contact angle and increasing wetting of the eye surface. Deficiencies can cause dry eye syndrome. Artificial tear fluids containing phospholipid surfactants are used for treatment.
HLB System
- Hydrophilic-Lipophilic Balance: A numerical scale (0-50) that measures the balance between the hydrophilic and lipophilic properties of a surfactant.
- Useful for predicting surfactant behavior in emulsions:
- Lower values (0-3): Anti-foaming agents
- 4-6: W/O emulsifying agents
- 7-9: Wetting agents
- 8-18: O/W emulsifying agents
- 13-15: Detergents
- 10-18: Solubilizing agents
- Bancroft's Rule: The emulsifier is more soluble in the continuous phase. This suggests that W/O emulsions require surfactants with a higher lipophilic character (lower HLB).
Calculating HLB Values
- Two main methods:
- Griffin's Method: Based on the lipophilic portion's molecular mass relative to the total molecule.
- Davies' Method: Considers the hydrophilicity of various hydrophilic groups.
HLB System: Applications
- Anti-Foaming Agents: (HLB 1-3) Reduce surface tension of gas bubbles in foams, causing them to collapse and coalesce.
- W/O Emulsifying Agents: (HLB 4-6) Reduce surface tension between oil and water, forming stable globules, preventing separation. Example: Span 60.
- Wetting Agents: (HLB 7-9) Lower the contact angle between a surface and a liquid, displacing air and facilitating wetting of the surface. Example: Bile salts.
- O/W Emulsifying Agents: (HLB 8-18) Reduce surface tension between oil and water, forming stable globules, preventing separation. Example: Tween 80.
- Detergents: (HLB 13-15) Facilitate mixing of hydrophobic compounds (oil/grease) with water, reducing interfacial tension and aiding in cleaning. Example: Sodium lauryl sulfate.
- Solubilizing Agents: (HLB 10-18) Increase solubility of poorly soluble materials by forming micelles. The lipophilic core of the micelle traps the poorly soluble substance, allowing it to dissolve in the aqueous solution.
HLB System: Common Surfactants
- Spans: Sorbitan esters
- Tweens: Polyoxyethylene sorbitan fatty acid esters
- Often used in combination.
HLB System: Oil and Oil-like Substances
- Oils and oil-like substances also have assigned HLB values. These values depend on whether the oil is used in an O/W or W/O emulsion.
- To create a stable emulsion, the emulsifier (surfactant) should have an HLB value similar to the oil phase, depending on the desired emulsion type.
- HLB values for blends of surfactants are calculated additively, considering the proportion of each surfactant.
HLB System: Practice Problem
- Example formulation: Cetyl alcohol, white wax, anhydrous lanolin, emulsifier, glycerin, distilled water.
- To determine the appropriate emulsifier HLB:
- Calculate the HLB of the oil phase using a weighted average based on the HLB values of each oil-phase ingredient.
- Choose or calculate the blend of surfactants required to achieve the desired HLB.
- The appropriate HLB will depend on the desired type of emulsion (O/W or W/O):
- O/W emulsion: The HLB value of the emulsifier should be higher (closer to 12)
- W/O emulsion: The HLB value of the emulsifier should be lower (closer to 5).
Preparation of Emulsions: Equipment
-
Small Scale:
- Mortar and pestle
- Beakers
- Blenders
- Mixer
- Hand homogenizer
- Prescription bottles
-
Large Scale:
- Mixing tanks with high-speed impellers
- Colloid mill or large homogenizers
Emulsification Using Acacia
- Popular natural emulsifier obtained from Acacia trees.
- Two major methods for emulsification:
- Continental or Dry Gum Method
- English or Wet Gum Method
Emulsification
- Emulsifier ratio: 4 parts fixed oil : 2 parts water : 1 part emulsifier
- Volatile oil ratio: 2 parts volatile oil : 2 parts water : 1 part emulsifier
Continental or Dry Gum Method
- Forms a thick primary emulsion with a snapping sound
- Acacia is first dispersed in oil
- Part of water is added at once with rapid trituration
- Remaining aqueous phase is then added slowly with trituration
English or Wet Gum Method
- Same proportions as dry gum method, but different order of mixing
- Acacia is first dispersed in water to form a mucilage
- Oil is then added slowly with rapid trituration
- The remaining water is then added slowly with trituration
- Slower and less reliable than the dry gum method
- Useful if the emulsifier is only available as a solution or must be dissolved before use
Selecting Emulsifiers
- HLB values are additive for blends of emulsifiers
- Tweens and Spans are commonly used
Emulsification using Surfactants
- Bottle or Forbes method: Ingredients are shaken together in a closed prescription bottle, suitable for volatile oils and oils with low viscosities
- Beaker method: Ingredients are heated separately then combined, suitable for oils with high viscosities
- In situ soap emulsions: Prepared by beaker or bottle methods, based on calcium or soft soaps
In situ soap emulsions: Calcium soaps
- W/O emulsions
- Equal amounts of olive oil and lime water are mixed to form calcium oleate
- May require excess olive oil for a homogeneous emulsion
- Acid addition can destroy the emulsion by shifting the equilibrium towards the undissociated acid form
In situ soap emulsions: Soft soaps
- O/W emulsions
- Water soluble and water dispersible
- Salts of fatty acids with K+, Na+, or NH4+
- Give emulsions with a basic pH
- Unsuitable for internal use due to taste and laxative effects
Addition of Drugs to Emulsions
- Best to incorporate during emulsion formation
- Oleaginous materials are added to the oil phase
- Aqueous materials are added to the water phase
Emulsion Type: O/W
- Can be diluted with water
- Water-soluble dye diffuses uniformly
- Conducts electricity
Emulsion Type: W/O
- Cannot be easily diluted with water
- Water-soluble dye does not diffuse uniformly
- Does not conduct electricity
Emulsion Instability
- Creaming: Separation into two regions with different internal phase concentrations, reversible by shaking
- Coalescence/Cracking/Breaking: Irreversible breakdown of the emulsifying film surrounding droplets
- Phase inversion: Conversion to the opposite emulsion type, triggered by temperature extremes
Preservation of Emulsions
- Preservatives are partitioned between oil and water phases
- Bacteria grow in the water phase
- Fungistatic preservatives are recommended for o/w emulsions
- Common preservatives: methyl and propyl paraben, alcohol 12-15%
Commercially Available Products
- Oral: Fish oil emulsions, Microlipid®, Liquigen®
- Ophthalmic: Restasis® (cyclosporine)
- Injectable: Intravenous fat emulsions (IVFE), Dipravan® (propofol), Cleviprex® (clevidipine)
Microemulsions
- Large micelles containing the internal phase
- Optically transparent
- Droplets in internal phase: 10-200 nm diameter
- Uses: more efficient drug absorption, topical drug delivery, cosmetics
Commercially Available Microemulsions
- PropoClear® (propofol)
- Neoral® (cyclosporine)
Suspensions
- Multi-phase systems with finely divided solid particles dispersed in a vehicle
- Routes: oral, topical, otic, ophthalmic, rectal, IM/SC
- Never given IV
- Reasons for preparation: chemical stability, taste masking, insolubility
Features of a Good Suspension
- Pours readily and evenly
- Small, uniform particle size (typically 1-5 microns)
- Particles settle slowly and redisperse easily
- Settled particles do not form a cake
Flocculation & Deflocculation
- Flocculation: Formation of light fluffy aggregates held together by weak forces, easily reversible by shaking
- Deflocculation: Particles remain dispersed, sediment slowly
Sedimentation Volume
- Ratio of sediment volume to initial suspension volume
- F generally ranges from 0 to 1
- Ideally, F=1 with no sedimentation or caking
Degree of Flocculation
- Ratio of sedimentation volume to the ultimate volume of a completely deflocculated suspension
Velocity of Sedimentation
- Defined by Stokes’ Law
- Factors: particle size, density, viscosity
- Controlled settling achieved by reducing particle size, increasing viscosity, preventing aggregation
Suspensions
- Deflocculated suspensions are ideal but may lead to issues with viscosity, density, and accurate dosing
- Flocculated suspensions are a compromise and offer benefits such as easier redispersion and can be achieved through controlled slow sedimentation.
- Sedimentation rate of particles is affected by factors such as particle size and density, as well as viscosity and density of the suspending medium.
- The formulation of suspensions involves two key steps: ensuring particle dispersion and wetting, and then selecting an appropriate suspension vehicle.
- Wetting agents like glycerin, propylene glycol, and surfactants assist in creating uniform dispersion and promote wetting.
- Structured vehicles increase viscosity and slow down sedimentation.
- Controlled flocculation uses flocculating agents which promote loose aggregation of suspended particles, maximizing sedimentation volume and preventing cake formation.
- Flocculating agents can include electrolytes, polymers, clays, and surfactants.
- Flocculation within structured vehicles combines the benefits of both methods, but requires considering potential incompatibilities between agents.
- Oral suspension dosage forms consist of different components, including active ingredients, wetting agents, dispersion medium, suspending agents, sweeteners, flavors, flocculating agents, and preservatives.
Suspension Preparation
- Particle size reduction is achieved by crushing tablets or emptying capsule contents into a mortar.
- Wetting the particles involves adding a wetting agent slowly and triturating to form a paste
- Final volume adjustment is achieved by adding the selected vehicles slowly and ensuring the total volume is accurate.
Suspension Approaches
- Deflocculated suspensions involve dispersing particles, which results in an uniform dispersion of deflocculated particles.
- Flocculated suspensions can be the final product, or they can be made using structured vehicles for improved stability.
- Flocculated suspensions in structured vehicles provide a balanced solution with controlled flocculation and the advantages of a structured vehicle.
Polymorphism
- Polymorphism refers to the ability of a substance to exist in different crystalline forms.
- Meta-stable polymorphs can convert to stable forms over time, potentially affecting solubility, dissolution rate, and bioavailability.
Packaging and Storing Suspensions
- Light-resistant, airtight containers are recommended for compounded products.
- Refrigeration is often necessary unless stability data dictates otherwise.
- Adequate airspace above the liquid is needed to allow for proper shaking.
- Containers should have large enough openings to allow for easy pouring.
- Shaking before use is essential, and appropriate labeling should indicate the need to "shake well before using" or "shake well and keep in the refrigerator."
Marketed Suspension Products
- Many marketed oral and topical products are suspensions.
- Dry powders for oral suspension, primarily antibiotic-based, are reconstituted with purified water.
- Delayed release suspensions contain granules that release the drug after administration.
- Extended release suspensions release the drug over an extended period of time, providing sustained therapeutic effects.
Gels
- Gels are semi-solid systems consisting of dispersions of small inorganic particles or large organic molecules enclosed within a liquid.
- Two types of gels exist: single-phase and two-phase, both classified as colloidal dispersions.
- Single-phase gels, also known as mucilages, contain soluble organic macromolecules with a continuous phase of aqueous, hydroalcoholic, or non-aqueous liquids.
- Two-phase gels consist of a network of small, discrete particles, forming a gel-like consistency.
- Magmas are suspensions of inorganic substances, such as clays, with a gel-like consistency and thixotropic rheological behavior.
- Milks are suspensions in aqueous vehicles used for oral and topical administration.
- Single-phase gels are molecular dispersions with no apparent boundaries between macromolecules and the liquid.
- Two-phase gels consist of floccules of small, distinct particles.
- Syneresis refers to the expulsion of liquid from a gel, leading to shrinkage.
- Imbibition is the displacement of one fluid by another immiscible fluid.
- Swelling is the increase in volume as elastic forces in macromolecules expand.
- Examples of single-phase gels include tragacanth (natural gum), methylcellulose (semi-synthetic cellulose), and carbomer gels (synthetic macromolecules).
- Two-phase gels exhibit thixotropic behaviour and include aluminum hydroxide gel (AlternaGEL®).
- Magmas are often used as thickeners, for example, Bentonite magma NF found in Calamine lotion.
- Milks are suspensions in aqueous vehicles used for oral and topical administration.
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Test your knowledge on multi-phase systems, particularly emulsions and surfactants. This quiz covers properties, functions, and characteristics associated with these systems. Perfect for anyone studying chemistry or related fields.
