solutions and suspensions

What are disperse systems composed of?

disperse phase and a continuous phase

What size are dispersions considered colloidal?

• Dispersions w/ size of 1nm-1micrometre are considered colloidal

What causes movement of particles and droplets in colloidal instability?

Gravity

What causes aggregation of particles and droplets?

Attractive interparticle forces

What is coalescence?

Droplets merging

What is Ostwald ripening?

Crystal growth

. What dispersed phase and product example are paired: solid drug particles in liquid?

Oral suspension e.g. amoxicillin suspension or calamine lotion

What dispersed phase and product example are paired: oil droplets in water?

Creams, lotions or parenteral lipid emulsions

What dispersed phase and product example are paired: water droplets in oil?

Water in oil creams/ointments

What dispersed phase and product example are paired: liquid droplets of solid particles in gas?

Inhalers/aerosol sprays

What dispersed phase and product example are paired: gas bubbles in liquid/semi-solid?

Medicated foams e.g. topical foam formulations

What is a solution?

Homogeneous mixture of 2 or more components

What states can solute and solvent exist in?

Solid, liquid or gaseous states

What commonly acts as the solvent in solutions?

Water

Name some solvents used to dissolve APIs.

Glycerol, ethanol, PEG

. Why must solvents be used to dissolve APIs?

To avoid precipitation

Name four pharmaceutical solution types.

Aromatic waters, elixirs, spirits, syrups

What are tinctures?

Traditional pharmaceutical solutions

What routes can solutions be administered by?

Oral, otic, ocular, nasal, pulmonary, rectal, vaginal, parenteral

What additional requirements depend on route of administration?

Sterility, palatability, isotonicity etc

Give two advantages of pharmaceutical solutions.

API is dissolved and dose uniformity

Why may solutions act faster than solid dosage forms?

Solvent fuelled

What manufacturing advantage do solutions have?

Generally easy to manufacture

Why are APIs in solutions often unsuitable?

APIs are inherently unstable

What solubility issue affects many APIs in solutions?

Poor solubility in water

Why are liquid formulations less portable?

Liquids are bulky

has impact on environmental sustainability as well as convenience to pt

What water type is used when medicines do not need to be sterile/apyrogenic?

Purified water

How is purified water prepared?

Distillation, ion exchange or reverse osmosis

What is highly purified water used for?

Medicines where biology quality needed

What does water for injections need to be free from?

Pyrogen

What is sterilised water for injections used for?

Medicines administered parenterally

What characteristics does sterilised water for injections have?

Sterilised and packaged appropriately

Why is potable water not typically used in medicine manufacture?

Contains dissolved substances affecting formulation stability

What may potable water be used for?

Reconstitution of oral solutions

Name common excipients in pharmaceutical solutions.

Cosolvents, flavourings, colouring agents, sweeteners (sucrose, mannitol, saccharin, xylitol etc) , preservatives

Name functional excipients used in solutions.

Antioxidants, viscosity enhancers, chelating agents, pH adjusters, isotonicity adjusters

Give examples of antioxidants.

Sodium metabisulphite, sodium sulphite, ascorbic acid

Give examples of viscosity enhancers.

Hypromellose, PVA, povidone, dextran, carbomer 940

What can enhance drug solubility?

pH adjustments, cosolvents, cyclodextrins, surfactants/micelles

What is a suspension?

Liquid system containing Dispersion of solid material (the dispersed phase) in a liquid (continuous phase)

What particle size do pharmaceutical products contain?

• Pharmaceutical products: particles typically 0.1-10micrometres

What particle size do colloidal dispersions contain?

<1 micrometre

Are pharmaceutical products usually colloidal suspensions?

No

What particle shape is ideal in suspensions?

Monodisperse spheres

Why are monodisperse spheres preferred?

Reproducibility

What characterises a stable system?

Particles rebound and remain freely dispersed

What keeps particles dispersed in stable systems?

Repulsive forces

Why do particles in disperse systems interact frequently?

Large total surface area

What happens when particles aggregate?

Temporary or permanent attachment

What determines particle interactions?

Balance of attractive and repulsive forces

What contributes to VR in DLVO theory?

Adsorption of charged polymers, inorganic ions, polarity difference, ionisation

What contributes to VA in DLVO theory?

Van der Waals forces

What is the DLVO equation?

Voverall = VA + VR

What happens when particles approach each other in DLVO theory?

Attractive and repulsive forces act

What is aggregation?

Collection of particles into groups

What drives aggregation?

Forces of attraction

What is coagulation?

Particles closely aggregated

What happens to vehicle in coagulation?

Vehicle trapped

Why is coagulated sediment difficult to pour?

Vehicle trapped makes it difficult

What effect does shaking have on coagulated aggregates?

May deform aggregate

Why is coagulated sediment difficult to redisperse?

Dense aggregates formed

What is deflocculation?

Particles remain separated

Where does deflocculation occur on interaction energy curve?

Primary minimum

How do particles appear in a deflocculated system?

Very small

What sediment is formed in deflocculation?

Compact sediment

Why is deflocculated sediment difficult to redisperse?

High van der Waals attraction

What is flocculation?

Secondary minimum aggregation

What size aggregates are formed in flocculation?

Large loose aggregates

Why is flocculated sediment easy to redisperse?

Loosely packed structure

What does shaking do in a flocculated system?

Redisperses sediment into homogeneous system

Fill this in

What factors can be controlled to maintain flocculated state?

Particle size, particle density, vehicle density, vehicle viscosity

What law describes terminal settling velocity?

Stoke’s law

What factors can alter suspension stability?

Zeta potential change, pH, electrolytes

What causes bridging flocculation?

Surface active agents, polyvalent electrolytes, hydrophilic polymers

What is steric stabilisation?

Stabilisation by surface adsorbed polymers

What should be considered first when assessing solubility?

Appropriate volume for dosage form

What effect does increasing solvent amount have on solubility issues?

Very little effect

Is aqueous solubility or non-aqueous solubility generally preferred?

Aqueous solubility

Why is aqueous solubility generally preferred?

Better suppresses solubility

Name excipients used in suspensions.

Flavours, sweeteners, colours

What are antifoams used for?

Prevent foaming

What are buffers used for?

pH control

What are chemical stabilisers used for?

Antioxidants

What are density and viscosity modifiers used as?

Suspending agents

What is flocculation modifier commonly used?

NaCl

What do colloidal stabilisers do?

Stabilise dispersions

How do surface wetting surfactants reduce surface tension?

Increase contact between solvent and solid

What is the result of improved contact between solvent and solid?

Improved dispersion

How do solutions and suspensions differ?

Physical characteristics, pharmaceutical properties and stability

Why may solutions be preferred over suspensions?

Better bioavailability and dose uniformity

Why may suspensions be preferred over solutions?

Increased stability and tastability

What pharmaceutical principle explains suspension settling?

Stoke’s law

Why is understanding dispersion systems important?

To predict formulation behaviour and maintain stability throughout shelf life and administration timeframes