W1 L4 - Liquid Dosage Forms and their Applications (Emulsions and Suspensions) Flashcards
what’s an emulsion
- a dispersion of two immiscible liquids
- stabilised by an emulsifying agent
two types of emulsion
- oil-in-water (O/W) emulsion (i.e. oil droplets dispersed in water)
- water-in-oil (W/O) emulsion (i.e. water droplets dispersed in oil)
role of emulsifying agents
- reduce free energy (surface/interfacial tension) of the oil/water interface this decreases energy required to prepare emulsion (easier to break up oil into small droplets) + increases stability
- stabilise droplets in emulsion
- thermodynamically unstable so will return to separate oil and water phases over time
affinity of emulsifier
has affinity for both oil and water typically a surfactant
Types of emulsifying agents (3)
- natural - promote emulsification by increasing viscosity of aq phase
- finely divided solid emulsifiers - promote emulsification by adsorbing at the interface layer and increasing viscosity of aq phase
- synthetic emulsifiers - promote emulsification by lowering interfacial tension between the oil and water phases by coating droplets
How to make an emulsion
- water + oil
- energy in-put = hand-shaking, high-speed mixing…
- higher energy in-put, smaller droplets
excipients used in formulations (8)
- antioxidants
- viscosity enhancers
- thickening agents
- preservatives
- oral emulsions
- sweetening
- flavouring
- colouring agents
types of emulsion ( in regards to droplet size)
- emulsion
- nanoemulsion
- microemulsion (smallest droplet size)
what’s needed to make nanoemulsions and what’s their stability
- more emulsifier and energy needed to produce - more expensive
- good level of stability but still unstable
microemulsions (smallest) - size, stability,appearance, amount of surfactant needed, how its made
- droplet size < 100 nm
- droplets of uniform size
- clear appearance
- thermodynamically stable
- can be made by simple mixing
- requires a high amount of surfactant
nanoparticles and emulsions - size, stability, appearance, amount of surfactant needed, how its made
- droplets > 100nm
- droplets are polydisperse (different size droplets)
- slightly to very cloudy appearance
- thermodynamically unstable
- energy needed for their formation
- requires a lower amount of surfactant
Parenteral (injectable) emulsions
- used intravenously or intramuscularly (parenterally)
- droplet size no more than 0.5μm as oil isn’t miscible so could block capillaries
Excipients used in emulsion formulations
- auxiliary emulsifying agents
- viscosity enhancers
- flavouring agents
- sweetening
- colouring agents
- antioxidants
- preservatives
Advantages of pharmaceutical emulsions
- incorporate poorly water-soluble drugs and improve the bioavailability
- mask unpleasant tastes or odours of oils and active substances
- due to the reduced size of the dispersed phase, absorption of drugs may be improved
disadvantages of pharmaceutical emulsions
- their poor stability
- emulsions are thermodynamically unstable and will return over time to separate oil and water phase
- need to shake emulsion before use to ensure that it is intact
What’s a suspension
- a dispersion of an insoluble solid material (typically drug) distributed throughout a fluid vehicle.
types of suspension
- colloidal
suspensions/nanosuspensions - transparent or translucent - coarse suspension - cloudy
two phases in suspensions
- dispersed phase (insoluble powder)
- continuous phase (vehicle – mostly aqueous)
How to make a suspension
- energy in-put = trituration (mortar and pestle), high speed mixing….
- higher energy, smaller particle size
properties of suspensions - size, stability, appearance, amount of stabiliser needed, how its made
- particles > 1 um
- particles are polydisperse
- suspension very cloudy appearance
- thermodynamically unstable
- can be made quite simply by trituration (grinding or crushing something into a fine powder)
- requires a small amount of stabilizer
properties of nanosuspensions - size, stability, appearance, amount of stabiliser needed, how its made
- particle size < 1 um
- particle of uniform size
- cloudy appearance
- thermodynamically unstable but more stable than a suspension
- a high amount of energy required
- requires a higher amount of stabilizer
Reasons to formulate a drug as a suspension
- no solvent available to dissolve the drug
- to mask taste of the drug
- to control the release of the drug
- if the drug is unstable in an aqueous medium
For oral suspension
- some drugs unstable in water
- therefore supplied as dry powders for reconstitution (the process of restoring something dried to its original state by adding water to it) at the time of dispensing
- provided with a definite expiry date of the suspension
Oral suspension
- suspensions that do not require reconstitution at the time of dispensing
Properties of suspensions to ensure uniform dose
- particles settle slowly
- particles are readily and uniformly redispersed upon shaking
- particle size remains consistent over time
- viscosity is high enough to ensure a uniform dose, but not so viscous that the suspension cannot be easily poured/measured from the bottle or injected
ingredients of an oral suspension
- drug (API)
- dispersion medium (water)
- excipients including stabilising agents
role of wetting agents
- reduce the interfacial tension between the particle surface and the dispersion medium
- improve dispersibility
role of suspending agent (thickening agent)
- helps overcome tendency of drug particles sedimenting over time
- increases viscosity
role of flocculating agents
- substances that help tiny particles in a liquid clump together (form “flocs”) s
- can be easily resuspended upon shaking
- prevent sedimentation at bottom of bottle
- examples - clays, electrolytes, surfactants
Preservation of antacid suspensions
- Antacid suspension pH (7.7–8.2) destabilizes methyl parahydroxybenzoate.
- Few preservatives are effective at this pH.
- Propyl parahydroxybenzoate can be used but needs extra precautions:
Use low-bioburden (few microorganisms present on material before sue) raw materials.
Prevent contamination during preparation.
Store in fridge.
Use small bottles.
Set a limited expiry date.
properties of solution
- preparation method is much simpler
- accuracy of dosage is better than disperse systems
- rate of absorption and bioavailability is greater
- tend to be much better tolerated
- suitable for parenteral infusion for instance
- more thermodynamically stable
properties of suspension
- can taste mask a drug because only dissolved API is unpalatable
- can increase stability of an API unstable in solution
- can reduce dissolution rate of an API if absorption needs to be slow down
Packaging for oral liquids
- plain amber glass/plastic bottles
- click-locks
- spoon vs syringe
- expiry
- may be available as measured doses in sachets
what are lotions
- are liquid or semi-liquid preparations
- are an aqueous suspension or an emulsion
- contain one or more active ingredients in vehicle
- have a cooling effect & are preferred to ointments/creams for application to hairy areas
- are intended to be applied to the unbroken skin without friction
properties of parenteral liquids
- injected into tissue
- intravenous injection can produce a rapid, clinical effect, and is often used in an emergency
- sterile
- pyrogen-free
- preservatives incorporated
- pH 7.4
- isotonicity :
large volumes – intravenous infusion
small volumes – if not isotonic, product can be tolerated as diluted by body fluids
Nasal liquid dosage forms
- nasal solutions are aqueous-based formulations in the form of droplets or sprays with pH in the ranges 5.5 - 6.5
- isotonic with nasal fluids
- solution viscosity is similar to that of nasal mucus
- nasal sprays can be in the form of emulsions or suspensions
- nasal canal highly vascularised
- drug absorption via microvilli
- drops cover larger SA than sprays
Otic (ear) liquid preparations
- includes solution and suspensions
- drops placed in ear canal
- no need for isotonicity due to wax
Ocular liquid preparations
- topical formulations deliver drugs eye’s surface
- intraocular dosage forms (i.e. drugs administered directly inside the eye via injection into the anterior or posterior cavity)
- ophthalmic dosage forms need to be sterile
Topical ocular liquid formulations
- Rapid action, short eye retention, must be sterile.
- Emulsions/suspensions used for poorly soluble or unstable drugs, or prolonged release.
- Multidose forms have preservatives.
- Eye tolerates pH 3.5–9; ideal ~7.4, small deviations okay.
- Polymers added to boost viscosity and retention time.
Pulmonary liquid preparations
Pulmonary liquids include nebulizers and aerosols.
- Delivered via face mask.
- Nebulizers use energy to form breathable droplets from a solution or suspension.
- Nebulizers must be sterile, isotonic, and have pH 3–8.5 (large volume delivery).
- Aerosols are two-phase systems (solid or liquid particles in gas).
- Pressurized metered dose inhalers (pMDIs) are the most common aerosols.
- In pMDIs, drug is dissolved or suspended in a propellant inside a pressurized, metered valve container.
Rectal liquid preparations
- liquid preparations for rectal use are called enemas and may be formulated as a solution, emulsion or suspensions
- they can be administered for their systemic effect local effect to
- evacuate,
- cleanse
- treat
- diagnostic purposes
- enemas can either be an aqueous or oily solution
- warmed to body temp before administration
