Dispersed Systems

Leigh Don T. Villanueva, RPh

De La Salle Medical and Health Sciences Institute
PH-PHR 214 A.Y. 2020-2021
Dispersed Systems
• Liquid preparation containing undissolved or immiscible drug
distributed throughout a vehicle.

PH-PHR 214: Dosage Forms, Drug Delivery Systems, and Medical Devices
Dispersed Systems
• Particles vary in size
• Coarse Dispersion (~10– 50 µm)
• Fine Dispersion (0.5 – 10 µm)
• Colloidal Dispersion (colloidal range)

PH-PHR 214: Dosage Forms, Drug Delivery Systems, and Medical Devices
Dosage Forms under Dispersed
Systems
Suspension
• A _____-phase system consisting of a finely divided solid
dispersed in a solid, liquid or gas
• Preparations containing finely divided drug particles distributed
somewhat uniformly throughout a vehicle in which the drug
exhibits a minimum degree of solubility
• Density of the particles is generally greater than that of the
vehicle

PH-PHR 214: Dosage Forms, Drug Delivery Systems, and Medical Devices
Features desired in a pharmaceutical suspension
• Particles should settle slowly and should be readily ________
upon gentle shaking of the container
• Particle size should remain __________ throughout long periods
of undisturbed standing
• Suspension should ______ readily and evenly from its container

PH-PHR 214: Dosage Forms, Drug Delivery Systems, and Medical Devices
Rheology
• The study of flow, addresses the viscosity characteristics of
powders, fluids, and semisolids
• Newtonian v. Non-Newtonian Flow

PH-PHR 214: Dosage Forms, Drug Delivery Systems, and Medical Devices
Stokes Equation
%
𝑑" 𝑑 𝜌' − 𝜌) 𝑔
=
𝑑𝑡 18𝜂

PH-PHR 214: Dosage Forms, Drug Delivery Systems, and Medical Devices
Features desired in a pharmaceutical suspension
• 10 to 50 μm size –micropulverization
• 10 μm -fluid energy grinding

PH-PHR 214: Dosage Forms, Drug Delivery Systems, and Medical Devices
Types of Suspension
• Aggregates
• Open
• Closed
• Dispersed

PH-PHR 214: Dosage Forms, Drug Delivery Systems, and Medical Devices
Suspension are available in
• Ready-to-use form
• Dry powder

PH-PHR 214: Dosage Forms, Drug Delivery Systems, and Medical Devices
Classification of Pharmaceutical Suspensions
• Orally administered mixtures
• Externally applied lotions
• Injectable Preparations

PH-PHR 214: Dosage Forms, Drug Delivery Systems, and Medical Devices
Applications/Advantages
• To supply solid drugs in liquid form
• To adjust the dose of the drug
• For insoluble or poorly soluble drugs
• For drugs that are unstable in an aqueous medium
• To improve stability
• To improve taste

PH-PHR 214: Dosage Forms, Drug Delivery Systems, and Medical Devices
Ingredients
• Active ingredient/s
• dispersion medium
• aqueous
• non-aqueous
• wetting agents
• suspending agents
• viscosity/density modifiers

PH-PHR 214: Dosage Forms, Drug Delivery Systems, and Medical Devices
Ingredients
• buffers
• flavors and sweeteners
• fragrances
• colors
• humectants
• preservatives

PH-PHR 214: Dosage Forms, Drug Delivery Systems, and Medical Devices
Wetting Agent
• suitable surfactant with HLB value between 7 and 9
• used at a concentration of 0.05 to 0.5%
• allow displacement of air from hydrophobic materials and
permit the liquid to surround the particles and disperse

PH-PHR 214: Dosage Forms, Drug Delivery Systems, and Medical Devices
Suspending Agents
• carboxymethylcellulose, methylcellulose, microcrystalline
cellulose, poly(vinylpyrrolidone), xanthan gum, bentonite

PH-PHR 214: Dosage Forms, Drug Delivery Systems, and Medical Devices
Preparation
• Method 1
• triturate the drug
• add wetting agent
• add suspending agent in the aqueous medium containing other
soluble ingredients
• Method 2
• triturate the drug and the dry suspending agent with the wetting agent
• bring to volume with the diluent water
• triturate to a smooth uniform product

PH-PHR 214: Dosage Forms, Drug Delivery Systems, and Medical Devices
Preparation
• Colloid Mills or homogenizers may be used after the
suspension is formed to reduce particle agglomerates

PH-PHR 214: Dosage Forms, Drug Delivery Systems, and Medical Devices
Preparation
• Preparations from Tablets

PH-PHR 214: Dosage Forms, Drug Delivery Systems, and Medical Devices
Emulsions
Emulsion
• two-phase systems in which one liquid is dispersed throughout
another liquid in the form of droplets
• Internal phase -the dispersed phase
• External phase or dispersion medium -continuous phase

PH-PHR 214: Dosage Forms, Drug Delivery Systems, and Medical Devices
Theories of Emulsification
• Surface Tension Theory
• Oriented Wedge Theory
• Plastic/Interfacial Film Theory

PH-PHR 214: Dosage Forms, Drug Delivery Systems, and Medical Devices
Application
• Enhance the stability of drugs
• Enhance palatability of oil and oil-soluble substances that are
to be administered orally
• Enhance the absorption of drugs
• Permits administration of drugs in minute globules rather than
in bulk
• Suitability for topical application of drugs
• W/O emulsions are occlusive and emollient
• O/W emulsions are water-removable

PH-PHR 214: Dosage Forms, Drug Delivery Systems, and Medical Devices
Advantages
• Increased therapeutic properties and spreading ability of the
constituents
• Masking of unpleasant taste or odor
• More control of absorption and penetration of medicaments

PH-PHR 214: Dosage Forms, Drug Delivery Systems, and Medical Devices
Types of Emulsion
• Oil-in-Water Emulsion (O/W)
• Water-in-Oil Emulsion (W/O)
• Multiple Emulsion
• Microemulsions

PH-PHR 214: Dosage Forms, Drug Delivery Systems, and Medical Devices
Types of Emulsion
• Multiple Emulsion
• dispersed phase contains even smaller droplets that are miscible with
the continuous phase
• O/W/O –aqueous phase is between two oil phases
• W/O/W –internal and external phases are separated by an oil phase

PH-PHR 214: Dosage Forms, Drug Delivery Systems, and Medical Devices
Types of Emulsion
• Microemulsions
• Thermodynamically stable, optically transparent isotropic mixtures of
a biphasic o/w system stabilized with surfactants
• translucent or transparent emulsions with droplet sizes in the
nanometer size range
• Dispersions of oil stabilized with surfactants

PH-PHR 214: Dosage Forms, Drug Delivery Systems, and Medical Devices
Emulsion Appearance
Droplet Size Appearance
>1μm Milky
0.1 - 1μm Blue-white
0.05 – 0.1μm Gray, semi-transparent
<0.05μm Transparent

PH-PHR 214: Dosage Forms, Drug Delivery Systems, and Medical Devices
Ingredients
• Water
• Oil
• Emulsifying Agents
• Viscosity Agents
• Preservative
• Flavoring and Sweetening Agents
• Fragrances
• Colorants

PH-PHR 214: Dosage Forms, Drug Delivery Systems, and Medical Devices
Emulsifying Agents
• Primary agents
• Natural Emulsifying Agents
• Finely Divided Solids
• Synthetic Emulsifying Agents

PH-PHR 214: Dosage Forms, Drug Delivery Systems, and Medical Devices
Natural Emulsifying Agents
• Low surface activity, increases the viscosity of the aqueous phase
• Vegetable sources
• Acacia, tragacanth, alginates, chondrus, pectin
• Animal sources
• Gelatin, egg yolk, casein, wool fat, cholesterol, lecithin

PH-PHR 214: Dosage Forms, Drug Delivery Systems, and Medical Devices
Finely Divided Solids
• Absorbed at the interface, increases the viscosity usually of the aqueous
phase
• Used frequently for external preparations
• Colloidal clays
• Bentonite (aluminum silicate)
• Veegum (magnesium aluminum silicate)

PH-PHR 214: Dosage Forms, Drug Delivery Systems, and Medical Devices
Synthetic Emulsifying Agents
• Most effective at lowering interfacial tension between the oil and the
water phases because their molecules possess both hydrophilic and
hydrophobic properties
• Anionic –sodium dodecyl sulfate
• Cationic –benzalkonium chloride
• Nonionic –polyethylene 400 monostearate
• Ampholytic –long-chain amino acid derivatives

PH-PHR 214: Dosage Forms, Drug Delivery Systems, and Medical Devices
HLB System
• A method whereby emulsifying or surface-active agents may
be categorized on the basis of their chemical make-up as to
their hydrophile-lipophile balance
• Each agent is assigned an HLB value or number which is
indicative of the substance’s polarity. Materials that are highly
polar or hydrophilic are assigned higher numbers than
materials that are less polar and more lipophilic.

PH-PHR 214: Dosage Forms, Drug Delivery Systems, and Medical Devices
HLB System
HLB Range Use Examples

1-3 Antifoaming Agents Span 65

4-6 W/O emulsifier Oleic acid, Span 60

7-9 Wetting Agent Span 20, Acacia

8-18 O/W emulsifier Polysorbate 80, Gelatin, Methocel

13-15 Detergents Tween 40, Tween 60

10-18 Solubilizing Agents SLS, Sodium oleate

PH-PHR 214: Dosage Forms, Drug Delivery Systems, and Medical Devices
HLB System
• Generally, agents having an HLB value of 3-6 are greatly
lipophilic and produce water-in-oil emulsions. Those with HLB
values of 8-18 produce oil-in-water emulsions

PH-PHR 214: Dosage Forms, Drug Delivery Systems, and Medical Devices
• Wetting agent –aid in attaining intimate contact between solid
particles and liquid (HLB 7-9)
• Emulsifying agent –reduce interfacial tension between oil and
water (HLB 3-6 or 8-18)
• Detergents –reduce surface tension and aid in wetting the
surface and the dirt. The soil is emulsified and foaming
generally occurs (HLB 18-20)

PH-PHR 214: Dosage Forms, Drug Delivery Systems, and Medical Devices
Viscosity Agent
• Auxiliary agents
• Emulsion stabilizers
• Hydrophilic in nature and dissolve or disperse in water to
give a viscous solution
• Gums, cellulose derivatives, carbomer polymers

PH-PHR 214: Dosage Forms, Drug Delivery Systems, and Medical Devices
Other Ingredients
• Flavoring and Sweetening Agents
• Fragrances
• Colorants
• Humectants

PH-PHR 214: Dosage Forms, Drug Delivery Systems, and Medical Devices
Preparation of Emulsions
Equipment
• Mortar and pestle
• Hand-operated homogenizer
• Ultrasonic device

PH-PHR 214: Dosage Forms, Drug Delivery Systems, and Medical Devices
Methods of Preparation
• Continental or Dry Gum Method
• English or Wet Gum Method
• Bottle Method
• Auxiliary Method
• In Situ Soap Method
• Microemulsions

PH-PHR 214: Dosage Forms, Drug Delivery Systems, and Medical Devices
Continental or Dry Gum Method
• 4:2:1 method for preparing the initial or primary emulsion
• By volume: 4 parts oil, 2 parts water, 1 part gum
• Wedgewood or porcelain mortar and pestle

PH-PHR 214: Dosage Forms, Drug Delivery Systems, and Medical Devices
Continental or Dry Gum Method
Triturate emulsifier and oil

Add water and triturate

Primary emulsion: Creamy white; crackling sound

PH-PHR 214: Dosage Forms, Drug Delivery Systems, and Medical Devices
Continental or Dry Gum Method
Add liquid ingredients that are miscible with the external phase

Dissolve solid ingredients first before adding to the mixture

Add water to volume

PH-PHR 214: Dosage Forms, Drug Delivery Systems, and Medical Devices
English or Wet Gum Method
• 4:2:1 method for preparing the initial or primary emulsion
• By volume: 4 parts oil, 2 parts water, 1 part gum
• Wedgewood or porcelain mortar and pestle

PH-PHR 214: Dosage Forms, Drug Delivery Systems, and Medical Devices
English or Wet Gum Method
Triturate emulsifier and water

Add oil and triturate

Primary emulsion: Creamy white; crackling sound

PH-PHR 214: Dosage Forms, Drug Delivery Systems, and Medical Devices
English or Wet Gum Method
Add liquid ingredients that are miscible with the external phase

Dissolve solid ingredients first before adding to the mixture

Add water to volume

PH-PHR 214: Dosage Forms, Drug Delivery Systems, and Medical Devices
Bottle Method
• Forbes Bottle Method
• For emulsions with volatile oils or oleaginous substances with
low viscosity
• Not for viscous oils: inadequate mixing

PH-PHR 214: Dosage Forms, Drug Delivery Systems, and Medical Devices
Bottle Method
Place emulsifier and oil in a bottle; cap and shake thoroughly

Add a portion of water and shake thoroughly, repeat until all water has been added

Add water to volume. Aqueous solution of other ingredients may be added

PH-PHR 214: Dosage Forms, Drug Delivery Systems, and Medical Devices
Auxiliary Method
• Use of hand homogenizer after preparing the emulsion
• Reduction of globule size to 5 microns
• Not for very thick emulsions
• Damage to the homogenizer valve

PH-PHR 214: Dosage Forms, Drug Delivery Systems, and Medical Devices
In Situ Soap Method
• For calcium soaps and soft soaps
• Calcium soap
• w/o emulsion that contain certain vegetable oils in combination with
limewater (Calcium Hydroxide Soln)
• Soft soap
• Liquid soap or soap that easily dissolves
• Oil phase is the external phase
• Occlusion and skin softening

PH-PHR 214: Dosage Forms, Drug Delivery Systems, and Medical Devices
Instability of Emulsions
• Creaming and Sedimentation
• Flocculation and Coalescence
• Phase Inversion

PH-PHR 214: Dosage Forms, Drug Delivery Systems, and Medical Devices
Gels
Gels
• Sometimes called jellies
• Semisolid systems consisting of either suspensions made up
of small inorganic particles or large organic molecules
interpenetrated by a liquid

PH-PHR 214: Dosage Forms, Drug Delivery Systems, and Medical Devices
Gels
• Two-Phase Gels
• Base for topical preparations
• Thixotropic –forms semisolids on standing and becoming liquid on
agitation
• Single-Phase Gels
• Semisolid state, high degree of clarity, ease of application, ease of
removal and use, faster release of drug
• Made from synthetic macromolecules or natural gums

PH-PHR 214: Dosage Forms, Drug Delivery Systems, and Medical Devices
Gels
• BP classification:
• Hydrophobic gels (oleogels)
• Hydrophilic gels (hydrogels)
• Syneresis
• Thixotropy
• Thermal gelation
• Xerogel

PH-PHR 214: Dosage Forms, Drug Delivery Systems, and Medical Devices
Lotion
• Either liquid or semisolid preparations that contain one or more
active ingredients in an appropriate vehicle
• Prepared by triturating the ingredients to a smooth paste and
then adding the remaining liquid phase with trituration

PH-PHR 214: Dosage Forms, Drug Delivery Systems, and Medical Devices
Magmas and Milk
• Aqueous suspensions of insoluble, inorganic drugs
• Thick and viscous and does not need a suspending agent
• Passing through a colloid mill is recommended to minimize
sedimentation on standing
• Require a “Shake Well” label and must not be stored in the
freezer

PH-PHR 214: Dosage Forms, Drug Delivery Systems, and Medical Devices
Magmas and Milk
• Magmas may also be described as suspensions of inorganic
acids such as clays in water where there is a tendency for
strong hydration and aggregation of the solid, giving rise to
gel-like consistency and thixotropic behavior
• Milk is also described as suspensions in aqueous vehicles
intended for oral administration

PH-PHR 214: Dosage Forms, Drug Delivery Systems, and Medical Devices
Aerosols
Aerosols
• Products that are packaged under pressure and contain
therapeutically active ingredients that are released upon
activation of an appropriate valve system.
• Intended for topical application to the skin as well as local
application into the nose (nasal aerosols), mouth (lingual
aerosols), or lungs (inhalation aerosols)

PH-PHR 214: Dosage Forms, Drug Delivery Systems, and Medical Devices
Types of Aerosols
• Two-phase (Gas and Liquid)
• Consists of a solution of active ingredients in liquefied propellant and
the vaporized propellant
• Three-phase (Gas, Liquid, and Solid or Liquid)
• Consists of a suspension or emulsion (foam aerosol) of the active
ingredient(s) in addition to the vaporized propellants

PH-PHR 214: Dosage Forms, Drug Delivery Systems, and Medical Devices
Components of and Aerosol System
• Container
• Propellant
• Concentrate containing the active ingredient(s)
• Valve
• Actuator

PH-PHR 214: Dosage Forms, Drug Delivery Systems, and Medical Devices
Components of and Aerosol System

PH-PHR 214: Dosage Forms, Drug Delivery Systems, and Medical Devices
Advantages
• A portion of the medication may be easily withdrawn from the
package without contamination or exposure to the remaining
material
• The aerosol container protects medicinal agents adversely
affected by atmospheric oxygen and moisture.
• The usual opaque container protects drugs adversely affected
by light. This protection persists during the use and the shelf
life of the product. If the container is packaged under aseptic
conditions, sterility may also be maintained.

PH-PHR 214: Dosage Forms, Drug Delivery Systems, and Medical Devices
Advantages
By proper formulation and valve control, the physical form and
the particle size of the product may be controlled, which may
contribute to the efficacy of the drug. (ex. Fine mist for
inhalants). Dosage may also be controlled through the use of
metered valves.

PH-PHR 214: Dosage Forms, Drug Delivery Systems, and Medical Devices
Advantages
• Aerosol application is a clean process, requiring little or no
wash up by the user.

PH-PHR 214: Dosage Forms, Drug Delivery Systems, and Medical Devices
Reference
Ansel, Howard, et al. Pharmaceutical Dosage Forms and Drug
Delivery Systems. 10th ed. USA: Lippincott Williams & Wilkins,
2014.

PH-PHR 214: Dosage Forms, Drug Delivery Systems, and Medical Devices
 Thank you for listening

Leigh Don T. Villanueva, RPh

De La Salle Medical and Health Sciences Institute
PH-PHR 214 A.Y. 2020-2021