W1 L2 - Liquid dosage forms and their applications (solutions) Flashcards
1
Q
What’s a suspension
A
Solid in liquid
2
Q
What’s an emulsion
A
Liquid in liquid
3
Q
What are the 2 types of liquid dosage forms
A
- Monophasic: solution
- biphasic: suspension and emulsion
4
Q
What’s a solution
A
- A homogenous mixture typically prepared by dissolving a solute in a solvent
- drug immediately available for action/absorption
- can be optically clear and transparent but can be coloured
- majority aren’t saturated
5
Q
Factors affecting solubility
A
- ionic strength
- pH - affects precipitation
- temperature - low temp low solubility
- solvent/co-solvent
- molecular structure - salts of drug more soluble than free acid/base
- particle size - smaller have larger SA
6
Q
Route of administration of solutions
A
- oral, otic, ophthalmic, or topical
7
Q
What’s potable water
A
- drinkable
- not for pharmaceutical use due to solutes
8
Q
What’s purified water
A
- water that has been mechanically filtered or processed to remove impurities and make it suitable for use
- used in preparation of water containing medicines except injections
9
Q
What’s water for for injection
A
- pyrogens removed (substances from microorganisms that cause fever)
- sterile and distilled
- used for injectables
10
Q
3 aqueous water solvents
A
- potable water
- purified water
- water for injection
11
Q
What are co-solvents
A
- water-miscible liquid
- less water than water and can dissolve hydrophobic drug
- less safe than water
- in low amount/conc due to toxicity
12
Q
examples of co-solvents
A
- glycerol
- propylene
- glycol
- ethanol
13
Q
ethanol (non-aqueous solvent)
A
- used when a drug is not soluble or stable in water
- dissolves many water-insoluble excipients (e.g., flavours and antimicrobial preservatives)
- forms a hydroalcoholic mixture with water (dissolve alcohol-soluble and water-soluble substances)
- can act as a co-solvent at a concentration up to 20% in oral solutions
- can act as a preservative at a concentration of 15% or greater
14
Q
FDA guidance on use of alcohol for OTCs
A
- restricted and appropriate warnings in the labelling
- babies and children may convulse as they can’t metabolise alcohol
- children under 6 - 0.5% alcohol content
- 6 to 12 years and adults - 10%
- limited to 2 weeks in children above 6 if NO positive risk-benefit balance is demonstrated
- no limits in amount/conc in Europe
15
Q
Glycerol
A
- contains three hydroxyl groups
- is used as a solvent or cosolvent with water in oral and injectable formulations
- Oral use: used as a solvent, cosolvent, sweetening agent, antimicrobial preservative, and viscosity-increasing agent
16
Q
Polyethylene glycols (PEGs)
A
- low molecular weight, water-soluble, low-immunogenicity, biocompatible
- immunogenicity - the ability of a substance that contains antigens to cause the body to make an immune response against that substance.
- biocompatibility - Ability to be in contact with a living system without producing an adverse effect
- are used as solvents or cosolvents with water or ethanol in injectable solutions
17
Q
what are excipients
A
pharmacologically inert ingredients added intentionally to a drug product (DP) for various functional roles
18
Q
what are preservatives and properties
A
- the ingredients that are utilized in order to improve the shelf life of products
- inhibit microorganism growth
- safe
- stable, biocompatible
- stable
- non-toxic
- non-sensitising
- Sensitisation is an allergic reaction to a particular or specific substance, which causes an interaction with the body’s immune system
- inexpensive
19
Q
examples of non-aqueous solvents
A
- glycerol
- polyethylene glycols (PEGs)
- ethanol
20
Q
Preservative choice
A
- site of use
- unionised possesses preservative capacity
- ionised unable to penetrate microorganisms
- acidic preservatives are less dissociated and more effective in acidic formulations
- alkaline less effective in acidic or neutral conditions and more effective in alkaline formulations
21
Q
mechanism of action of preservatives
A
- alter cell membrane permeability - lysis (complete or partial) and/or coagulation of cytoplasmic constituents
- inhibit cellular metabolism - interference with enzyme systems or cell wall synthesis, oxidation of cell parts or hydrolysis
22
Q
what are pH buffers used for
A
- used to modify and stabilise pH
- the pH of an oral liquid is important for flavour solubility and stability of the active substance and for preservation
- buffer selected to have a pKa value approximately equal to target pH
- citrate buffer used, and it is recommended if pH needs to be controlled over a relatively wide pH range of 2.5–6.5
- Injectables often formulated at a pH close to physiological pH (pH 7.4), if the pH is not near physiological pH can lead to irritation, pain, and phlebitis (inflammation of the vein)
23
Q
which chemical reactions affect stability
A
- oxidation
- hydrolysis
24
Q
how to prevent oxidation
A
- replace O2 in the bottle headspace with inert gas ( nitrogen)
- use amber glass/plastic bottle to block light
- glass bottles less permeable to O2
- adding chelating agents and antioxidants
25
Q
what are chelating agents
A
- form stable complexes with metal ions, reducing risk of the ions being involved in oxidative degradation reactions
- calcium disodium e.g.
26
Q
what are antioxidants
A
- ingredients that are preferentially oxidised instead
- ascorbic acid
27
Q
what are viscosity enhancers (gel formers/thickening agents)
A
- improve pourability
- should be appropriate for palatability
- shields taste buds from unpleasant taste
28
Q
what are organoleptic properties
A
refers to any sensory properties of a product:
- colour
- odour
- taste
- mouth feel
29
Q
role of colouring agents
A
- improve acceptability by patient
- may help with flavour identification
- must be soluble and compatible with API
- conc less than 0.1%
30
Q
role of flavouring and sweetening agents
A
- mask unpleasant taste improving acceptability
- soluble and compatible with API
31
Q
what are aromatic waters
A
- clear, saturated aq solutions of volatile oils or other aromatic/volatile substances
- gives flavour or odour
- may cause precipitation of v soluble salts
- short shelf-lives
- stored in airtight, ligh-resistant containers
32
Q
what are syrups
A
- viscous concentrates of aq solutions
- sucrose used as main sugar 65% to 85%: below 65 - microbial growth, above 85 - recrystallisation of sucrose
- improves taste and protects from bac growth
- sucrose can cause dental cavities so other sugars preferred
- taste-masking
- syrups used as vehicles in paediatrics due to no alcohol content
33
Q
what’s linctus
A
- for of syrup
- high proportion of sucrose
- coats throat alleviating irritation
- sipped without addition of water
34
Q
what are elixirs
A
- clear, hydroalcoholic liquids that have pleasant taste and sweet flavour
- ethanol and water composition
- less viscous than syrups as they have little sugar and viscosity enhancers
- small quantities of excipients compared to syrups
- due to alcohol: age restriction + drug and excipient incompatibilities
35
Q
advantages of oral solutions
A
- API homogeneously dispersed throughout product
- API is in solution and does not need to undergo dissolution (except suspension)
- dose of the active agent is easily and conveniently adjusted by using the appropriate volume
- solutions may be swallowed by patients who have difficulty taking tablets or capsules, as might be the case with paediatric or geriatric patients
36
Q
Disadvantages of oral solutions
A
- API more susceptible to chemical degradation so shorter shelf-life
- challenges for taste making
- heavier and take up more shelf space
- causes difficulty for patient - volume measurement for visually impaired, arthritis
- susceptible to microorganisms so preservatives used but may cause allergic reaction
