DISPERSED SYSTEMS LIQUIDS

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DRUGS

• defined as an agent intended for use in the diagnosis, mitigation, treatment, cure, or prevention of disease in humans or in other animals (Food, Drug, and Cosmetic Act, 1938)

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Drug product

• means a finished dosage form, for example, tablet, capsule, solution, etc., that contains an active drug ingredient generally, but not necessarily, in association with inactive ingredients (CFR21)

• The term also includes a finished dosage form that does not contain an active ingredient but is intended to be used as a placebo.

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Component

• means any ingredient intended for use in the manufacture of a drug product, including those that may not appear in such drug product

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Components of Drug Product:

Active Ingredients

+

Inactive Ingredients

Except PLACEBO w/c do not contain AI

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Active ingredient (AI)

• means any component that is intended to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease, or to affect the structure or any function of the body of man or other animals

• The term includes those components that may undergo chemical change in the manufacture of the drug product and be present in the drug product in a modified form intended to furnish the specified activity or effect.

• AKA: “Drug Substance” or “Active Pharmaceutical Ingredient (API)”

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Inactive ingredient

• means any component other than an active ingredient

• AKA: Excipients/ Additives/Pharmaceutical Adjuncts/Necessities

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Inactive ingredient

• are agents used to : ▫ Solubilize ▫ Suspend ▫ Thicken ▫ Dilute ▫ Emulsify ▫ Stabilize ▫ Preserve ▫ Color ▫ Flavor

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DRUG DELIVERY SYSTEM

• means of administering drugs as formulated preparations

formulations which provide a therapeutic amount of drug to the proper site in the body promptly and maintain the desired drug concentration

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DOSAGE FORM

• Formulation containing a specific quantity of active ingredient(s)in combination with one or more excipients

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ba

sed

on

ph

ysi

cal

sta

te

Solid

Powders and Granules

Capsules

Tablets

Liquid

Solutions

Dispersed Systems

Semisolid

Ointments

Creams

Gels

TDDS

Gas

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LIQUIDS

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SOLUTIONS

Aqueous solutions

Sweet and other Viscid Aqueous

Solutions

Non-Aqueous Solutions

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Aq

ueo

us

So

luti

on

s

Aromatic water

Aqueous Acids

Diluted Acids

Douches

Enemas

Gargles

Washes Mouthwashes

Juices

Solutions

Otic Solutions

Nasal Solutions Sprays

Irrigation Solutions

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Sweet and other Viscid

Aqueous Solutions

Syrups Honeys Mucilage Jellies

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NO

N-A

QU

EO

US

S

OL

UT

ION

S

Collodions

Elixirs

Glycerins

Inhalations and Inhalants

Liniments

Oleovitamins

Spirits

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LIQUIDS

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Dis

per

sed

Sy

stem

s

Coarse Dispersion

Suspensions

Emulsions

Fine Dispersion

Magmas

Gels

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SOLIDS

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CA

PS

UL

ES

Hard Gelatin

Capsules (HGC)

Soft Gelatin Capsules (SGC)

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SOLIDS

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TABLETS Compressed Tablets

Multiply Compressed Tablets

Sugarcoated Tablets

Film-coated Tablets

Gelatin-coated Tablets

Enteric-Coated Tablets

Buccal and Sublingual Tablets

Chewable Tablets

Effervescent Tablets

Molded Tablets

Tablet triturates

Hypodermic Tablets

Dispensing Tablets

Immediate-Release Tablets

Instantly Disintegrating or Dissolving Tablets

Extended Release Tablets

Vaginal Tablets

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Classification of Dosage Form

By Physical State

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Dispersed Systems

• types of liquid preparations containing undissolved or immiscible drug distributed throughout a vehicle

• In these preparations, the substance distributed is referred to as the dispersed phase, and the vehicle is termed the dispersing phase or dispersion medium

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Dispersed Systems

Coarse Dispersion

Suspensions

Emulsions

Fine Dispersion

Magmas

Gels

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Coarse Dispersion

• Dispersions containing coarse particles, usually 10 to 50 μm

• consist of at least two phases

▫ dispersed or internal phases (one or more )

▫ dispersion medium or vehicle (continuous or external phase )

• Preparations:

▫ suspensions

▫ emulsions

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Fine Dispersion

• Dispersions containing particles of smaller size (0.5 to 10 μm)

• Preparations:

▫ Magmas

▫ Gels

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Dispersed Systems: Coarse Dispersion

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SUSPENSIONS

• defined as preparations containing finely divided drug particles (the suspensoid) distributed somewhat uniformly throughout a vehicle in which the drug exhibits a minimum degree of solubility

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SUSPENSIONS

• are two-phase system consisting of an undissloved or immiscible material dispersed in a vehicle (solid, liquid, or gas).

• coarse dispersion containing finely divided drug particles distributed uniformly throughout the vehicle in which the drug exhibits a minimum degree of solubility

• requires suspending and dispersing agents to be diluted and agitated with a specified quantity of vehicle, usually purified water

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SUSPENSIONS

• the particle diameter is 1 to 50 μm

• Availability:

▫ Oral Suspension are available as dry powders intended for suspension in liquid vehicles

▫ for Oral Suspension are most frequently supplied as dry powder mixtures for reconstitution at the time of dispensing

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Reasons for Suspensions

• Stability

• Easy to administer

• Pallatability

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Features Desired in a

Pharmaceutical Suspension 1. A properly prepared pharmaceutical

suspension should settle slowly and should be readily redispersed upon gentle shaking of the container

2. The particle size of the suspensoid should remain fairly constant throughout long periods of undisturbed standing

3. The suspension should pour readily and evenly from its container

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Sedimentation Rate of the

Particles of a Suspension

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Stokes equation

• was derived for an ideal situation in which uniform, perfectly spherical particles in a very dilute suspension settle without producing turbulence, without colliding with other particles of the suspensoid, and without chemical or physical attraction or affinity for the dispersion medium

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Brookfield viscometer

• Measures viscosity by the force required to rotate a spindle in the fluid being tested

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Physical Features of the Dispersed

Phase of a Suspension • the particle diameter is 1 to 50 μm

• particle shape of the suspensoid should not induce caking and product stability

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Micropulverization

• one of the most rapid, convenient, and inexpensive methods of producing fine drug powders of about 10 to 50 μm size

• Micropulverizers are high-speed attrition or impact mills that are efficient in reducing powders to the size acceptable for most oral and topical suspensions

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Micropulverization METHODS:

• fluid energy grinding

• spray drying

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fluid energy grinding

• Aka: jet milling or micronizing • for still finer particles under 10 μm • PROCESS:

▫ the shearing action of high velocity compressed airstreams on the particles in a confined space produces the desired ultrafine or micronized particles

▫ The particles to be micronized are swept into violent turbulence by the sonic and supersonic velocities of the airstreams.

▫ The particles are accelerated to high velocities and collide with one another, resulting in fragmentation.

• employed when the particles are intended for parenteral or ophthalmic suspensions

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spray drying

• produces particles of extremely small dimensions

• Spray Dryer is a cone-shaped apparatus into which a solution of a drug is sprayed and rapidly dried by a current of warm, dry air circulating in the cone

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Physical Features of the Dispersed

Phase of a Suspension • the particle diameter is 1 to 50 μm

• particle shape of the suspensoid should not induce caking and product stability

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Pre-Formulation Consideration factors:

1. Wetting or wettability property

2. Particles interaction and behavior

3. Sedimentation rate

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Wettability Property

• Involves the affinity of the solid and the liquid portion of the suspension

• Aids to increase the wetting characteristics of powder:

1. Use of Surfactant to decrease the solid-liquid interfacial tension

2. Use dispersion aids for hydrophobic solids

Example:

Hydrophobic Polymers (sodium carboxymethylcellulose)

Water insoluble hydrophilic materials (bentonite, veegum)

Colloidal silica

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Particle interaction and behavior

• Sensitivity of electrolytes

• Flocculation occurs at the following ion concentration:

▫ For monovalent ions = 25-150 mmol/L

▫ For divalent ions = 0.5-2.0 mmol/L

▫ For trivalent ions = 0.01-0.1 mmol/L

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Types of Suspension Systems

1. Flocculated System

2. Deflocculated System

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Flocculated System

Aka: Coagulated System or Colloidaly Unstable System

Characteristics:

a) particles appears as floccules or like tufts of wool with loose fibrous structure

b) Forms a clear particle free supernatant liquid and a sediment

c) Exhibit a minimum of serious separation

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Deflocculated System

• Aka: Peptized System or Colloidaly Stable System

• Characteristics:

a) The particles settle as a dense sediment and becomes compact after a given time interval

b) Results in poor suspension

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Relative Properties of Flocculated and

Deflocculated Particles in Suspension FLOCCULATED DEFLOCCULATED

1. Particles form loose aggregates. 2. Rate of sedimentation is high, as particles

settle as a floc, which is a collection of particles.

3. A sediment is formed rapidly. 4. The sediment is packed loosely and

possesses a scaffold-like structure. Particles do not bond tightly to each other, and a hard, dense cake does not form. The sediment is easy to redisperse, so as to reform the original suspension.

5. The suspension is somewhat unsightly, due to rapid sedimentation and the presence of an obvious, clear supernatant region. This can be minimized if the volume of sediment is made large. Ideally, volume of sediment should encompass the volume of the suspension.

1. Particles exist in suspension as separate entities.

2. Rate of sedimentation is slow, as each particle settles separately and particle size is minimal.

3. A sediment is formed slowly. 4. The sediment eventually becomes very

closely packed, due to weight of upper layers of sedimenting material. Repulsive forces between particles are overcome and a hard cake is formed that is difficult, if not impossible, to redisperse.

5. The suspension has a pleasing appearance, as the suspended material remains suspended for a relatively long time. The supernate also remains cloudy, even when settling is apparent.

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Sedimentation Rate

• The velocity of sedimentation is directly proportional to the particle size and inversely proportional with the viscosity of the formulation

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Problems in Suspension:

1. Caking

formation of cement like substance due to small partcles

Irreversible process

Solution: Flocculated System

2. Sedimentation

The rapid settling of particles

Reversible Process

Solution: Suspending Agents

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Rheology

• the study of flow, addresses the viscosity characteristics of powders, fluids, and semisolids

• Two (2) general categories of materials flow: 1. Newtonian flow is characterized by

constant viscosity, regardless of the shear rates applied

2. non-Newtonian is characterized by a change in viscosity characteristics with increasing shear rates

Example materials include colloidal solutions, emulsions, liquid suspensions, and ointments

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three general types of

non-Newtonian materials 1. Plastic

2. Pseudoplastic

3. Dilatant

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Plastic

• Substances that exhibit plastic flow are called Bingham bodies

• Plastic flow does not begin until a shearing stress corresponding to a certain yield value is exceeded

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Pseudoplastic

• Pseudoplastic substances begin flow when a shearing stress is applied; therefore, they exhibit no yield value.

• With increasing shearing stress, the rate of shear increases; consequently, these materials are also called shear-thinning systems

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Dilatant

• Dilatant materials are those that increase in volume when sheared, and the viscosity increases with increasing shear rate.

• These are also called shear-thickening systems.

• Dilatant systems are usually characterized by having a high percentage of solids in the formulation.

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Stability Consideration of Suspension

• The physical stability of a suspension is normally assessed by the:

1. Measurement of its sedimentation rate

2. Measurement of the final volume or height of sediment

3. Ease of redispersion of the product

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Suspending Agents Used in the Formulation of

Pharmaceutical Suspensions

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Formulation of Suspensions

• Factors to be considered in formulating suspensions:

1. Type of suspension desired (flocculated or deflocculated)

2. Formulation adjuvants

3. Preparation techniques

4. Incompatiblities

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Type of suspension

Flocculated System Deflocculated System

• Reduction of interfacial tension Application of Surfactants SLS Sodium dioctyl succinate Nonionic Surfactants (spans,

tweens, carbowax) • Drainage of the preparation

especially for oral, parenteral, ophthalmic or topical useaddition of protective colloid Silica Gel (a form of

precipitated silicic acid upto 10% conc) topical prep’n

• Retardation of settling and agglomeration of the particles by functioning as an energy barrier minimizing interparticulate attraction and ultimate deflocculation

Modified cellulose polymer (CMC, methocel)

Proteins (gels)

Synthetic Polymers (carbopol) used in external lotions and gels prep’n

Clays (bentonite, veegum)

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Formulation adjuvants

• Dispersion medium

• Wetting agents

• Buffer

• Other adjuvants:

▫ Preservatives

▫ Colorants

▫ Flavorants

▫ Perfumes

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Methods of Manufacture/Preparation

of Suspension: 1. By dispersion method

2. By precipitation method

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Incompatibilities

• Formation of dark color

• Oil separation

• Chemical reaction

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Packaging and Storage of Suspension

• All suspensions should be packaged in widemouth containers having adequate airspace above the liquid to permit thorough mixing by shaking and ease of pouring

• Most suspensions should be stored in tight containers protected from freezing, excessive heat and light

• Should have the auxiliary label “SHAKE WELL before used” to ensure a uniform distribution of solid in the vehicle and thereby uniform and proper dosage

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Purposes of Suspension

• Sustaining effect

• Stability

• Taste

• Basic solubility

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Application of Suspension

• Low solubility of active ingredient • Patients difficulty to swallow (suspension vs solids) • Unpleasant taste • Rate of absorption • Rapid degeneration • Unstable in desired vehicle • Degraded drug in aqueous form but not in

nonaqueous • Bulk insoluble powder • Prolong release effect • Topical prep’n

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Formation of suspensions • The following steps may minimize stability problems 1. The particle size of all powders used in the formulation should be

reduced. 2. A thickening (suspending) agent may be used to increase viscosity.

Common thickening agents include alginic acid, bentonite, VEEGUM, methylcellulose, and tragacanth.

3. A levigating agent may aid in the initial dispersion of insoluble particles. Common levigating agents include glycerin, propylene glycol, alcohol, syrups, and water.

4. Flavoring agents and preservatives should be selected and added if the preparation is intended for oral use. Common preservatives include methylparaben, propylparaben, benzoic acid, and sodium benzoate. Flavoring agents may be any fl avored syrup or flavored concentrate

5. The source of the active ingredients (e.g., bulk powders vs. tablets or capsules) must be considered; if commercial dosage forms are used, the inactive ingredients must be considered and only immediate-release tablets or capsules should be used and not modified release, unless necessary and they can be used appropriately.

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Preparation of suspensions

1. The insoluble powders are triturated to a fi ne powder. 2. A small portion of liquid is used as a levigating agent, and the

powders are triturated until a smooth paste is formed. 3. The vehicle containing the suspending agent is added in divided

portions. A high-speed mixer greatly increases the dispersion. 4. The preparation is brought to the required volume using the

vehicle. 5. The final mixture is transferred to a “tight” bottle for dispensing

to the patient. 6. All suspensions are dispensed with a “shake well” label. 7. Suspensions are not filtered. 8. The water-soluble ingredients, including flavoring agents, are

mixed in the vehicle before mixing with the insoluble ingredients.

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Example of Suspension Formulation

Amount Function

Aluminum hydroxide gel, USP 6g Antacid

Sodium benzoate 0.5g Preservative

Sodium saccharin 0.005g Sweetener

Sorbitol 1.4 mL Viscosity builder

Peppermint oil 0.005 mL flavorant

Purified water, to make 60 mL Solvent

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Dispersed Systems: Coarse Dispersion

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EMULSION

• is a dispersion in which the dispersed phase is composed of small globules of a liquid distributed throughout a vehicle in which it is immiscible

• have dispersed particles ranging in diameter from 0.1 to 100 μm

• is a dispersed system containing at least two immiscible liquid phases

• Two (2) phases: 1. Internal or Discontinuous Phase the

dispersed phase 2. External or Continuous Phase the dispersion

medium

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Types of Emulsion

1) oil-in-water (O/W) emulsion

2) water-in-oil (W/O) emulsion

3) multiple emulsions

4) Microemulsions

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oil-in-water (O/W) emulsion

• emulsions with an oleaginous internal phase and an aqueous external phase

• oral products and external, washable products

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water-in-oil (W/O) emulsion

• emulsions having an aqueous internal phase and an oleaginous external phase

• used for external preparations when emollient, lubricating, or protective properties are desired

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multiple emulsions

three phases are present Forms:

W/O/W

O/W/O

In these “emulsions within emulsions,” any drug present in the innermost phase must now cross two phase boundaries to reach the external, continuous phase

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Microemulsions

• appear translucent or transparent

• have droplet diameter in the nanometer size range

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Detection of Emulsion type

1. Dilution Test The dilution method depends on the fact that an O/W

emulsion can be diluted with water and a W/O emulsion with oil

2. Conductivity Test An emulsion in which the continuous phase is aqueous

can be expected to possess a much higher conductivity than an emulsion in which the continuous phase is an oil

3. Dye-solubility Test The knowledge that a watersoluble dye will dissolve in the

aqueous phase of an emulsion while an oil-soluble dye will be taken up by the oil phase provides a third means of determining emulsion type

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FACTORS THAT DETERMINE

EMULSION TYPE 1. Emulsifier

▫ some emulsifiers form either w/o or o/w emulsions, others form only one type

2. Phase ratio (relative amounts of oil and water)

▫ phase present in greater concentration tends to be the external phase

3. Order of mixing

▫ the phase that is being added by portions tends to be the internal phase

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Purposes of Emulsion:

• Increased drug solubility

• Increased drug stability

• Prolonged drug action

• Improved taste

• Improved appearance

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Emulsifying Agent

Any compound that lowers the interfacial tension and forms a film at the interface can potentially function as an emulsifying agent. The effectiveness of the emulsifying agent depends

on its chemical structure, concentration, solubility, pH, physical properties, and electrostatic effect True emulsifying agents (primary agents) can

form and stabilize emulsions by themselves Stabilizers (auxiliary agents) do not form acceptable

emulsions when used alone, but assist primary agents in stabilizing the product (e.g., increase viscosity).

are either natural or synthetic

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Classification of Emulsifying Agents

1. Natural Emulsifying Agent

2. Finely Divided Solids

3. Synthetic Emulsifying Agent

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Natural Emulsifying Agent

• derived from animal or plant sources

▫ Animal:

Gelatin

egg yolk

casein

▫ Plant:

Acacia

Tragacanth

Pectin

cellulose derivatives

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Acacia

• forms a good, stable emulsion of low viscosity

• It tends to cream easily, is acidic, and is stable at a pH range of 2 to 10.

• Like other gums, it is negatively charged, dehydrates easily, and usually requires a preservative.

• It is incompatible with Peruvian balsam, bismuth salts, and carbonates

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Tragacanth

• forms a stable emulsion that is coarser than acacia emulsion

• It is anionic, is difficult to hydrate, and is used mainly for its effects on viscosity.

• Less than 1/10 of the amount used for acacia is needed.

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Agar

• is an anionic gum that is primarily used to increase viscosity.

• Its stability is affected by heating, dehydration, and destruction of charge.

• It is also susceptible to microbial degradation.

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Pectin

• is a quasi-emulsifier that is used in the same proportion as tragacanth

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Gelatin

• provides good emulsion stabilization in a concentration of 0.5% to 1.0%

• It may be anionic or cationic, depending on its isoelectric point.

▫ Type A gelatin (+), prepared from an acid-treated precursor, is used in acidic media.

▫ Type B gelatin (-), prepared from an alkali-treated precursor, is used in basic media.

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Methyl cellulose

• is nonionic and induces viscosity.

• It is used as a primary emulsifier with mineral oil and cod liver oil, and yields an o/w emulsion.

• It is usually used in 2% concentration.

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Carboxymethylcellulose

• is anionic and is usually used to increase viscosity

• It tolerates alcohol up to 40%, forms a basic solution, and precipitates in the presence of free acids.

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Finely Divided Solids

• Aka: CLAY

▫ Veegum -Magnesium aluminumsilicate

▫ Bentonite -Native Colloidal Hydrated Aluminum Silicate

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Synthetic emulsifying agents

• are anionic, cationic, or nonionic • Although these surfactants are amphiphilic

molecules, their lipophilic and hydrophilic regions are seldom inverse equals of each other

• Some surfactant molecules tend to be predominantly lipophilic, whereas others are predominantly hydrophilic.

• This imbalance is reflected in the hydrophilic–lipophilic balance (HLB) scale: ▫ The larger the HLB value, the more hydrophilic the

molecule.

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Anionic synthetic agents

• include sulfuric acid esters (e.g., sodium lauryl sulfate), sulfonic acid derivatives (e.g., dioctyl sodium sulfosuccinate), and soaps. Soaps are for external use.

• They have a high pH and are, therefore, sensitive to the addition of acids and electrolytes. ▫ Alkali soaps are hydrophilic and form an o/w

emulsion. ▫ Metallic soaps are water insoluble and form a w/o

emulsion. ▫ Monovalent soaps form an o/w emulsion. ▫ Polyvalent soaps form a w/o emulsion.

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Cationic synthetic agents

• are used as surface-active agents in 1% concentration

• They are incompatible with soaps

• e.g., benzalkonium chloride

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Nonionic synthetic agents

• are resistant to the addition of acids and electrolytes

a. The sorbitan esters known as Spans are hydrophobic in nature and form w/o emulsions.

b. The polysorbates known as Tweens are hydrophilic and tend to form o/w emulsions. They may form complexes with phenolic compounds.

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HYDROPHILIC–LIPOPHILIC BALANCE

(HLB) HLB Value Range Surfactant Application

0 – 3 Antifoaming agents

4–6 Water-in-oil emulsifying agents

7 – 9 Wetting agents

8 – 18 Oil-in-water emulsifying agents

13 - 15 Detergents

10 - 18 Solubilizing agents

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COMMONLY USED SURFACTANTS AND THEIR HYDROPHILIC–

LIPOPHILIC BALANCE (HLB) VALUES

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Preparation

A. Classical, acacia-stabilized emulsions are prepared by one of the following four methods:

1. Wet gum (English) method

2. Dry gum (continental) method

3. Bottle method

4. Nascent soap method

B. Emulsions stabilized by synthetic emulsifying agents are readily prepared by a two-phase procedure.

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Wet gum (English) method

• A primary emulsion of fixed oil, water, and acacia (in a 4:2:1 ratio) is prepared as follows: a. Two parts of water are added all at once to one part

of acacia. The mixture is triturated until a smooth mucilage is formed.

b. Oil is added in small increments (1 to 5 mL), with continuous trituration, until the primary emulsion is formed.

c. The mixture (an o/w emulsion) is triturated for another 5 mins.

d. The o/w mixture can then be brought to volume with water and mixed to achieve homogeneity.

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Dry gum (continental) method

• A primary emulsion of the fixed oil, water, and acacia (in a 4:2:1 ratio) is prepared as follows: a. Oil is added to the acacia, and the mixture is triturated

until the powder is distributed uniformly throughout the oil. Water is added all at once, followed by rapid trituration to form the primary emulsion.

b. Any remaining water and other ingredients are added to finish the product.

i. Electrolytes in high concentration tend to crack an emulsion. They should be added last and in as dilute a form as possible.

ii. Alcoholic solutions tend to dehydrate and precipitate hydrocolloids. They should be added in as dilute a concentration as possible.

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Bottle method

• a variation of the dry gum method used for volatile oils

• Oil is added to the acacia in a bottle.

• The ratio of oil, water, and acacia should be 3:2:1 or 2:1:1.

• The low viscosity of the volatile oil requires a higher proportion of acacia.

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Nascent soap method

• A soap is formed by mixing relatively equal volumes of an oil and an aqueous solution that contains a sufficient amount of alkali.

• The soap acts as an emulsifying agent. a. This method is used to form an o/w or a w/o emulsion,

depending on the soap formed. For example, olive oil, which contains oleic acid, is mixed with lime water during the preparation of calamine lotion to calcium oleate, an emulsifying agent.

b. A 50:50 ratio of oil to water ensures sufficient emulsion, provided that the oil contains an adequate amount of free fatty acid. Olive oil usually does. Cottonseed oil, peanut oil, and some other vegetable oils do not.

c. The addition of an acid destroys the emulsifying soap and causes the emulsion to separate.

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Emulsions stabilized by synthetic emulsifying agents are

readily prepared by a two-phase procedure.

1. Oil-miscible ingredients and water-miscible ingredients are separately admixed, using heat if necessary to ensure liquefaction and ease of mixing of each phase.

a. High melting point oil-miscible ingredients (e.g., waxes) are melted before lower melting point ingredients (e.g., oils) are added.

2. The two phases are heated to 70° to 80°C and then combined with stirring until the resultant emulsion has cooled.

a. In general, heat-labile or volatile ingredients should not be incorporated in the separate phases but in the resultant emulsion aft er it has cooled to about 40°C or less.

3. Further mechanical processing of the emulsion by a hand homogenizer, immersion blender, or other equipment may be warranted to improve the homogeneity and stability of the product.

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Incorporation of medicinal agents

A. Addition of a drug during emulsion formation

B. Addition of a drug to a preformed emulsion can present some difficulty, depending on the type of emulsion and the nature of the emulsifier

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Addition of a drug to a preformed emulsion can present

some difficulty, depending on the type of emulsion and

the nature of the emulsifier 1. Addition of oleaginous materials to a w/o emulsion presents no problem because of the

miscibility of the additive with the external phase. However, addition of oleaginous materials to an o/w emulsion can be difficult after emulsion formation.

a. Occasionally, a small amount of oily material is added if excess emulsifier was used in the original formation.

b. A small amount of an oil-soluble drug can be added if it is dissolved in a very small quantity of oil with geometric dilution techniques.

2. Addition of water or an aqueous material to a w/o emulsion is extremely difficult, unless enough emulsifier has been incorporated into the emulsion. However, addition of aqueous materials to an o/w emulsion usually presents no problems if the added material does not interact with the emulsifying agent. Potential interactions should be expected with cationic compounds and salts of weak bases.

3. Addition of small quantities of alcoholic solutions to an o/w emulsion is possible if the solute is compatible or dispersible in the aqueous phase of the emulsion. If acacia or another gum is used as the emulsifying agent, the alcoholic solution should be diluted with water before it is added.

4. Addition of crystalline drugs to a w/o emulsion occurs more easily if the drugs are dissolved or dispersed in a small quantity of oil before they are added.

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Formation and preparation of

emulsions 1. A mortar and pestle are frequently all the equipment

that is needed. 2. Electric mixers and hand homogenizers are useful for

producing emulsions after the coarse emulsion is formed in the mortar.

3. The order of mixing of ingredients in an emulsion depends on the type of emulsion being prepared (i.e., o/w or w/o) as well as the emulsifying agent chosen.

4. Preservatives. If the emulsion is kept for an extended period, refrigeration is usually sufficient. The preparation should not be frozen. If a preservative is used, it must be soluble in the water phase to be effective.

5. Flavoring agents. If the addition of a flavor is needed to mask the taste of the oil phase, the flavor should be added to the external phase before emulsification

MDALegaspi 2016

FLAVOR SELECTION GUIDE

Taste Masking Flavor

Salt Butterscotch, maple

Bitter Wild cherry, walnut, chocolate mint, licorice

Sweet Fruit, berry, vanilla

Acid Citrus

MDALegaspi 2016

PROBLEMS IN EMULSION

1. creamingupward

2. sedimentationdownward

3. aggregationglobules come together but do not fuse

4. coalescenceglobules come together and fuse

5. crackingcomplete separation

6. inversion o/ww/o vice versa

MDALegaspi 2016

GELS

• are semisolid systems consisting of dispersions of small or large molecules in an aqueous liquid vehicle rendered jelly-like by the addition of a gelling-agent

MDALegaspi 2016

PHENOMENA IN GELS

• Thixotropy is the ability of the gel to become fluid on agitation, only to resume their solid or semisolid state after remaining undisturbed for a period of time.

• Imbibition is the taking up of a certain amount of liquid without a measurable increase in volume

• Swelling is also the taking up of liquid by a gel but with an increase in volume.

• Syneres is phenomenon where liquid comes out of the gel and the gel shrinks

• Xerogel is formed when the liquid is removed from a gel and only the frameworkremains

MDALegaspi 2016

GLYCEROGELATINS

• are plastic masses containing

▫ glycerin (40%)

▫ water (35%)

▫ gelatin (15%),

▫ and an added medicinal substance (10%) such as zinc oxide

MDALegaspi 2016

MAGMAS / MILK

• A two-phase system gel consisting of floccules of small distinct particles

• ex. Milk of Magnesia / Magnesia Magma

MDALegaspi 2016