Lecture 20 - Dispersed Systems: Suspensions

Dr. Agrahari

What is a Dispersed System?

Mixture of two substances, where the Dispersed Phase (DP) is distributed throughout the Dispersion Medium (DM)

What is another term for the Dispersed Phase (DP)?

Dispersion Medium (DM)?

DP — DIScontinuous Phase, INternal Phase

DM — CONtinuous Phase, EXternal Phase

What form does the Dispersed Phase take in Suspensions?

Dispersion Medium?

DP — Solid

DM — Liquid

What type of Dispersion is a Suspension?

Is it Heterogeneous or Homogeneous?

What is the size of the DP particles?

How fast is sedimentation?

Coarse Dispersion

Heterogeneous Dispersed System

>1000 nm Particles

Relatively Fast Sedimentation

What are the 5 main routes of administration for Suspensions in Pharmacy?

Give an example of each.

1. Oral — Antacid

2. Ocular — Tobradex; Tobramycin and Dexamethasone Ophthalmic Suspension

3. Topical — Calamine Lotion

4. Rectal — Mesalamine Rectal Suspension

5. Parenteral — Aristospan; Triamcinolone Hexacetonide Injectable Suspension

What is a Suspension?

What is the DP?

DM?

Heterogeneous system consisting of two phases, in which insoluble drug is dispersed throughout the dispersion medium

DP — Insoluble solid drug particles

DM — generally aqueous; may be an oily liquid

What are some advantages to having a Suspension as the Drug Form?

Include any specific examples that demonstrate each advantage.

1. Difficulty swallowing other drug dosage forms (oral Paracetamol susp. for pediatrics)

2. Allows us to dispense unstable drugs in solution form; improves chemical stability (AMOXIL)

3. Given for BOTH systemic and local therapeutic effects (MAALOX)

4. Used for both Topical / Dermatological application (MAXIDEX; Calamine)

5. Drugs exhibit HIGHER BIOAVAILABILITY than other forms, except for solutions

What is the order of Bioavailability for the dosage forms? (Highest to Lowest)

1. Solution

2. Suspension

3. Capsule

4. Compressed Tablets

5. Coated Tablets

What are some of the disadvantages of having a Suspension as a dosage form?

1. Uniform and accurate dose is hard to achieve

2. Difficult to formulate

3. Sedimentation and Compaction can cause problems

Explain the Theory of Suspension.

SETTLING AND AGGREGATION may result in formation of cakes that are difficult to RESUSPEND / PHASE SEPARATION

therefore,

suspensions are PHYSICALLY UNSTABLE due to particle-particle interactions and caking, which determines the stability of the suspension

What are three significant components of the interaction between the DP and the DM (in a suspension)?

1. Sedimentation (suspending agent)

2. Wetting of the Solid Phase (wetting agent)

3. Electrokinetic Potential (flocculating agent)

What is Sedimentation?

How is Sedimentation Velocity expressed?

Sedimentation — settling of particles that occurs under gravitational force in liquid dosage form

Expressed by Stoke’s Law

v = [ d² (ps - po) g / 18 no ]

What factors affect sedimentation?

1. Particle Size Diameter — INCreased Size = INCreased Sedimentation Rate

2. Density Difference between DP and DM

3. Viscosity of the DM — INCreased Viscosity = DECreased Sedimentation Rate

How does particle size affect sedimentation rate?

INCreased particle size = INCreased sedimentation rate

Larger Particles — settle faster and create a GRITTY TEXTURE + IRRITATION

Smaller Particles — easily form HARD CAKES

How does difference in density between the DP and DM affect Sedimentation?

If density of DM is GREATER than DP (ps < po), then there will be NON-UNIFORM DISTRIBUTION; PARTICLES FLOAT

If density of DM is the SAME as DP (ps = po), rate of settling becomes ZERO

How does the Viscosity of the DM affect Sedimentation?

HIGH Viscosity = LOW Sedimentation Rate

If we have too LOW of Viscosity, it will pour too fast

If we have too HIGH of Viscosity, we will be unable to get it out of the bottle

What is Comminution?

What is it used to facilitate?

Comminution — grinding of a solid, in which particle size of a solid substance is reduced to a finer state

Used to facilitate an INcrease in dissolution rates of a drug and ENhance absorption

What is Levigation?

When is it usually used?

Levigation — formation of a PASTE by combining the powder and a small amount of liquid LEVIGATING AGENT, in which the powder is insoluble

Commonly used in small scale preparations to reduce particle size and grittiness of added powders

What is another technique used for reduction of particle size in Suspensions?

Jet Milling — results in fine drug particles

What is a Structured Vehicle?

What does it form?

What happens when it is shaken?

Suspending medium that contains thixotropic compounds / polymers, which are pseudo-plastic or plastic in nature

Form a 3D gel network structure that entraps particles so NO SETTLING OCCURS

When shaken, the gel network is destroyed to facilitate administration

What is a Suspending Agent?

Give examples of common Suspending Agents.

Suspending Agent — viscosity modifier or thickening agent

Examples:

• Natural Hydrocolloids (Acacia, Tragacanth, Carrageenan)

• Semisynthetic Hydrocolloids (Methylcellulos)

• Synthetic Hydrocolloids (Carbopol)

• Clays (Bentonite, Veegum)

How do Hydrocolloids acts as Suspending Agents?

Hydrophilic Colloids coat Hydrophobic drug particles in one or more laters

What are some common examples of Vehicles / Suspending Mediums?

Deionized Water, Alcohol, Glycerol, Non-Aqueous Vehicles (Sesame, Almond, or Peanut Oil)

What two kinds of Solids can Insoluble Medicaments be?

1. Diffusible Solids

2. Indiffusible Solids

What are Diffusible Solids?

1. Light and easily wetter by water

2. Stay dispersed long enough for an adequate dose to be measured

3. After settling, they redisperse easily

What are Indiffusible Solids?

1. Not easily wetted

2. Some particles may form large, porous clumps in the liquid

3. Other particles may remain on the surface

How do we ascertain the Wettability of a powder?

How do we modify it?

Observe the contact angle and spreading coefficient

Modified by adding wetting agent

How does a Reduction in Surface Tension affect Wettability?

1. Reduction in Surface Tension

2. Movement of Solvent is promoted throughout the Medium

3. Good dispersal of Particles throughout the medium takes place

4. Increased Wettability

What do Contact Angles depend on?

What is the Contact Angle for complete wetting?

Depend on the surface tensions of the liquid, the solid, and the interfacial tension between them

For complete wetting, the contact angle = 0

What are Wetting Agents?

Surfactants that assist in wetting by lowering the contact angle

What is the main problem with Wetting Agents?

What two things can be used to fix this problem?

It is difficult to disperse solid particles in a liquid vehicle due to the layer of adsorbed air on the surface

So, particles float on the surface of the liquid until the later of air is displaced completely

Fixed via:

1. Surfactants

2. Glycerin / other similar Hygroscopic Substances

How do Surfactants fix the problem we have with Wetting Agents?

What are some examples of Surfactants we use?

Reduces the interfacial tension between solid particles and the vehicle

LOWERS Contact Angle, displacing air from surface of particles and promoting wetting

Examples:

• Polysorbate 80 (parenteral and oral)

How does Glycerin / other similar hygroscopic substances fix the problem we have with Wetting Agents?

What are some examples of these that we use?

Flow into the voids between particles, displacing the air and reduce the liquid-air interfacial tension

Water can then penetrate and wet the individual particles

Examples:

• Polyethylene Glycol (PEG)

• Polypropylene Glycol

What is Zeta Potential?

What is it useful in determining?

Zeta Potential — measure of the magnitude of electrical charge at the Electrical Double Layer; expressed the magnitude of repulsive forces between particles

Useful in determining stability of Liquid formulations

What are we concerned with controlling when developing a suitable suspension product?

1. Rate of Settling

2. Ease of Redispersion

3. Prevention of Caking (particles as a dense mass)

What is a Flocculated Suspension?

How do they compare sedimentation rate-wise to normal suspensions?

Flocs (loose aggregates) are formed, increasing Sedimentation Rate due to increased size of sedimenting particles

INCreased sedimentation rate (Sediment more rapidly) and settle as an aggregate

What is a Deflocculated Suspension?

Individual particles settle, slowing rate of sedimentation

This prevents entrapping of the liquid DM, making it difficult to redisperse by Agitation (‘Cracking’ phenomenon)

What are Flocculating Agents used for?

How do we control Flocculation?

Give some examples of Flocculating Agents we use.

Used to enhance particle ‘redispersability’

Control flocculation by adding Flocculating Agents

Examples:

• Electrolytes

• Surfactants

• Polymers

What types of Surfactants are used as Flocculating Agents?

Give examples of each.

1. Anionic — Alkali Soaps (Na or K Oleate), Amine Soaps (triethanolamine stearate), or Detergents / Alkyl Sulfates (Sodium Lauryl Sulfate)

2. Cationic — Benzalkonium Chloride or Benzethonium Chloride

3. Nonionic — Spans or Tweens

How do Polymers act as Flocculating Agents?

Part of the polymer chain is adsorbed onto the particle surface, with the remaining parts projecting into the DM

How are Suspensions evaluated?

What two parameters are useful for Suspension evaluation?

Evaluated by determining their Physical Stability

1. Sedimentation Volume (F)

2. Degree of Flocculation (B)

What is Sedimentation Volume?

How is it expressed?

Of a suspension, it is expressed as the Ratio of the eq. Volume of Sediment (Vu) to the Total Volume of the Suspension (Vo)

F = Vu / Vo

What do each of the F values indicate?

• F = 1

• F = 0.5

• F > 1

F = 1 —> no sedimentation, no clear supernatant

F = 0.5 —> 50% of the total volume is occupied by sediment

F > 1 —> sediment volume is greater than the original volume due to formation of floccules, which are fluffy and loose