W1 L4 - Liquid Dosage Forms and their Applications (Emulsions and Suspensions) Flashcards
1
Q
what’s an emulsion
A
- a dispersion of two immiscible liquids
- stabilised by an emulsifying agent
2
Q
two types of emulsion
A
- 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)
3
Q
role of emulsifying agents
A
- reduce free energy of the oil/water interface this decreases energy required to prepare emulsion + increases stability
- stabilise droplets in emulsion
- thermodynamically unstable so will return to separate oil and water phases over time
4
Q
nature of emulsifier
A
has affinity for both oil and water typically a surfactant
5
Q
Types of emulsifying agents (3)
A
- 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
6
Q
How to make an emulsion
A
- water + oil
- energy in-put = hand-shaking, high-speed mixing…
- higher energy in-put, smaller droplets
7
Q
excipients used in formulations (8)
A
- antioxidants
- viscosity enhancers
- thickening agents
- preservatives
- oral emulsions
- sweetening
- flavouring
- colouring agents
8
Q
types of emulsion ( in regards to droplet size)
A
- emulsion
- nanoemulsion
- microemulsion (smallest droplet size)
9
Q
naoemulsions
A
- more emulsifier and energy needed to produce - more expensive
- good level of stability but still unstable
10
Q
microemulsions
A
- droplet size < 100 nm
- droplets of uniform size
- clear appearance
- thermodynamically stable
- can be made by simple mixing
- requires a high amount of surfactant
11
Q
nanoparticles and emulsions
A
- droplets > 100nm
- droplets are polydisperse
- slightly to very cloudy appearance
- thermodynamically unstable
- energy needed for their formation
- requires a lower amount of surfactant
12
Q
Parenteral (injectable) emulsions
A
- used intravenously or intramuscularly (parenterally)
- droplet size no more than 0.5μm as oil isn’t miscible so could block capillaries
13
Q
Excipients used in emulsion formulations
A
- auxiliary emulsifying agents
- viscosity enhancers
- flavouring agents
- sweetening
- colouring agents
- antioxidants
- preservatives
14
Q
Advantages of pharmaceutical emulsions
A
- 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
15
Q
disadvantages of pharmaceutical emulsions
A
- 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
16
Q
What’s a suspension
A
- a dispersion of an insoluble solid material (typically drug) distributed throughout a fluid vehicle.
17
Q
types of suspension
A
- colloid/colloidal suspensions/nanosuspensions - transparent/translucent
- coarse suspension - cloudy/turbid
18
Q
two phases in suspensions
A
- dispersed phase (insoluble powder)
- continuous phase (vehicle – mostly aqueous)
19
Q
How to make a suspension
A
- energy in-put = trituration (mortar and pestle), high speed mixing….
- higher energy, smaller particle size
20
Q
suspensions
A
- particles > 1 um
- particles are polydisperse
- suspension very cloudy appearance
- thermodynamically unstable
- can be made quite simply by trituration
- requires a small amount of stabilizer
21
Q
nanosupensions
A
- 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
22
Q
Reasons to formulate a drug as a suspension
A
- no solvent available to dissolve the drug
- to task mask the drug
- to control the release of the drug
- if the drug is unstable in an aqueous medium
For oral suspension - certain drugs are unstable in the presence of water for prolonged periods of time
- 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
23
Q
Properties of suspensions to ensure uniform dose
A
- 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
24
Q
ingredients of an oral suspension
A
- drug (API)
- dispersion medium (water)
- excipients including stabilising agents
25
Q
role of wetting agents
A
- reduce the interfacial tension between the particle surface and the dispersion medium
- improve the flow and increase the dispersibility and homogeneity of the drug particles within the suspension
26
Q
role of suspending agent (thickening agent)
A
- helps overcome tendency of drug particles sedimenting over time
- increases viscosity
27
Q
role of flocculating agents
A
- create an open, large volume sediment (or floc) that can be easily resuspended upon shaking
- prevent sedimentation at bottom of bottle
- examples - clays, electrolytes, surfactants
28
Q
Preservation of antacid suspensions
A
- pH of an antacid suspension is 7.7 - 8.2
- unfavourable for stability & effectiveness of methyl parahydroxybenzoate
- no other preservatives are useful in this pH range
- propyl parahydroxybenzoate can be used but additional measures are needed to achieve a reasonable shelf life
to overcome…
use raw materials with a low bioburden
prevent contamination during preparation
store in the fridge
small bottles
limited expiry date
29
Q
solution
A
- preparation method is much simpler
- accuracy of dosage is better than disperse systems
- rate of absorption and bioavailability is be greater
tend to be much better tolerated - suitable for parenteral infusion for instance
- more thermodynamically stable
30
Q
suspension
A
- 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
31
Q
Packaging for oral liquids
A
- plain amber glass/plastic bottles
- click-locks
- spoon vs syringe
- expiry
- may be available as measured doses in sachets
32
Q
what are lotions
A
- 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
33
Q
Parenteral liquids
A
- 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
- iconicity :
large volumes – intravenous infusion
small volumes – if not isotonic, product can be tolerated as diluted by body fluids
34
Q
Nasal liquid dosage forms
A
- 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
35
Q
Otic (ear) liquid preparations
A
- includes solution and suspensions
- drops placed in ear canal
- no need for isotonicity due to wax
36
Q
Ocular liquid preparations
A
- 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
37
Q
Topical ocular liquid formulations
A
- rapid onset of action
- short retention time and rapid drainage from the eye
- sterile
- less common are ocular emulsions and suspensions, needed when drugs have
- low solubility in aqueous vehicle,
- exhibit chemical stability issues,
- when the hydrophobic drug is more potent than
its water-soluble salt or - when a prolonged drug release is required
- multidose preparations formulated with antimicrobial preservatives
- the eye can tolerate a pH ranging from 3.5 to 9
- isotonic with tears (pH 7.4) – although some deviation can be tolerated when small volumes of solutions are administered as the solution is rapidly diluted by the patient’s tears
- polymers are added as a viscosity modifier to increase the ocular solution’s residence time in the eye
38
Q
Pulmonary liquid preparations
A
- nebulizers and aerosols
- delivered via a face mask
- application of energy (from the nebulizer) into the nebulizer solution or suspension, results in the formation of droplets that the patient breaths in
- nebulizers must be sterile, isotonic, with a pH in the range 3 - 8.5 as they are often delivered as a large volume
- aerosols are two-phase systems compromising solid particles or liquid droplets dispersed in a gas
- pressurized metered dose inhalers (pMDI) are the most commonly used aerosol
- in a pMDI drug is dissolved or suspended in a propellant (i.e. a liquefied gas) and is filled into a pressurized container fitted with a metered valve
39
Q
Rectal liquid preparations
A
- 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 or
- treat
- diagnostic purposes
- enemas can either be an aqueous or oily solution
- warmed to body temp before administration
