D. Pharmaceutics Flashcards
What are ‘specials’?
Medicines made for
individual patients with special
needs that can not be met by
licensed medicines
What features are present on the ‘main label’ in ‘specials manufacturing’?
- Dose, frequency and other instructions
- Storage instructions
- Discard unused contents after….
(the expiry date) - Date of manufacture
- Batch number
- Patient name
What features are present on a ‘ancillary label’?
- BNF WARNINGS
- KOOSAROC - for ALL meds
- Shake the bottle - for ALL liquid meds
- Use this medicine only on your skin - for ALL Skin meds
- Not to be taken - On non-skin products that are not to be
swallowed e.g. eye drops, ear drops
How do you decide on an expiry date for a special?
- The instabilities of the ingredients
- The stability of the medicine itself
- The protection provided by the packaging
- Any risks of microbial contamination during use e.g. eye drops or creams in a jar
Why store in a cool place?
To protect against instabilities like heat, microbiological
growth, volatile
ALL powder meds must be stored in a cool place
Why store in a dark place?
To protect against instabilities like oxidation and light.
Why store in a dry place?
To protect against instabilities like moisture.
A medicine containing water should not be stored in a
Why store in a tightly sealed container?
To protect against instabilities like moisture and air
What are some routes of administration for bulk powders?
- Dusting powders
- Nasal spray
- Dry powders inhaler
How are oral bulk powders packaged?
In a jar or vial
How are oral bulk powders taken?
- Either spoonfuls of powder dispersed in water, milk, …or
sprinkled onto food sprinkled on food - reconstituted in water before dispensing- useful when the drug is unstable in water
What are the advantages of sachets over bulk containers?
- More accurate dosing
- better protection against moisture,
- more convenient
What are the advantages of oral bulk and wrapped powders over tablets or liquids?
- Patients who have difficulties swallowing tablets or capsules
- more stable that liquid meds
- can give large doses orally
- fast dissolution and action
What are the disadvantages of powders?
- They are hygroscopic so they can cake
- can seperate- due to different size particles and vibration from transport, mixing and pouring
- can have poor flow, which is hard to pack
Features of a hard capsules
- Hard polymer shell soluble in water
(gelatin or HPMC) - Two parts: body and cap
What are hard capsules filled with?
- Powder mixture
- Small tablets
- Granules
- Combinations
(ex: powder + tablet)
What are the advantages of hard capsules?
*easy to swallow
*easier to manufacture than tablets
*different sizes
*Some can be opened
*shell protects the powder
Shell can sometimes mask taste
*shell can be coloured better identifying or delayed release
What are the features of tablets
- Coating (optional)
- drug + excipientsb in the core (matrix)
- print (name or other writting)
- break line
What are the advantages of tablets?
- small, portable, convenient
- very stable (no water, coating so lower risk of hydrolysis)
- shape and colour give a distinct market identity
How do tablets release drugs in the body?
- disintegrants/ disintegrating agents absorbs water and swells tablet
- tablets breaks into small pieces and dissolve so that the drug is in solution
- the drug crosses the gut wall by absorption
- drug in bloodstream
- distributed in the body
- therapeutic effect
How do capsules release drugs in the body?
- The polyer shell of the capsule dissolves in the GI fluid
- powder released and drug dissolves
- drug crosses the gut wall by absorption
- drug in bloodstream
- distributed around the body
- therapeutic effect
What are the different types of tablets?
- Dispersible/ effervescent
- Immediate release
- Extended release
What are the features of dispersible tablets?
- Dissolve in water / or on tongue
- fast acting
- effervecsent mixture or thin porous tablets
Features of Immediate release tablets
- Disintegrates and releases drug in stomach
- fast acting
How do delayed release tablets work?
- remain intact in the stomach
- disintegrates in the small intestine
- enteric coating is insoluble in acid but soluble at neutral pH (in intestine)
- coating is sometimes called enteric coating
What is a delayed release tablet?
A tablet that is resistant to stomach acid
When are delayed release tablets used ?
- If the drug degrades in the stomach
- irritates the stomach
- once a day dose is required
- fast drug release causes side effects
How are extended release drugs designed?
- A insoluble porous coating
OR - a matrix that erodes slowly
What are the different types of liquid medicines?
- Solutions
- Suspensions
- Emulsions
What are solutions?
- Soluble liquid + soluble liquid
OR - soluble solid + soluble liquid
What is a suspension?
Insoluble solid + liquid
What is an emulsion?
Insolule liquid + liqiud
What are the types excipients in liquid medicines?
- Vehicles
- stabilisers-preservs,antiox,buffers
*Appealers-flavours,sweetners,colours - specifc to types-thickners,solubility enhancers, emulsifying agents
What is a vehicle?
The main liquid ingredient
What are common vehicles in liquid meds? And function
- water
- thick sweet liquids-more palatable, pourability
glycerol,syrup,sorbitol solution
- other liquids e.g. alcohol, ether, propylene glycol
Preservatives are to prevent what in liquid meds?
- growth of microbes
- food poisoning
- contamination
- mircrobes degrading the meds
What antioxidants do in liquid meds?
- more easily oxidised so prevents oxidation of drug favouring the unionised form
- terminates oxidation/free rad reactions
What are some examples of water soluble antioxidants?
- Ascorbic acid (vit c)
- Sulphites
- SO2
What are chelating agents used for and give an example
Reduce the ability of heavy metal ions from catalysing oxidation reactions
e.g. EDTA
Why is it important to control the pH of the medicine?
- specific solubility requirements
- to prevent dregradation
- effectivness of excipients
- safety
- taste
What are some sweetners and characteristics of them.
- Sugars-causes tooth decay, preservative if undiluted
- Glycerol - demulcent (prevent irr)
- Sugar alcohols- not calorie free, can causes diarrhoea, cramps, bloating
- Artificial sweetners - possibly carcinogenic
What are flavours use for in liquid meds?
Mask taste
What do solubility emhancers do in liquids meds?
Help the drug and excipients to dissolve
E.g. micelles, cosolvents
What are two physical stability problems with suspensions?
- seperation- particles fall to the bottom due to gravity
- caking- particles bound together
Risks of ununiform suspensions
- low drug content at the top
ineffective/ sub-therapeutic - High drug content at the bottom
Overdose
How to prevent seperation and caking
- Shake medicine
- decrease particle size
- Increase vicosity of the vehicle by adding a thickening agent/suspending agent
- Flocculate, adjusting surface charge
*add a surfactant
What are the 3 types of stability of medicines?
- Chemically
- Physicallly
- Microbiologically
What are some examples of changes in chemical, physical and microbial properties?
- amount of drug
- seperation, caking
- rate of drug release
- microbial contamination
What is the definition of shelf life?
The extent to which a medicine retains, within specified limits, and throughout its shelf life, the same properties and characteristics that it possessed at the time its manufacture.
What does ‘specified limits’ mean for the meds?
Specified limits are the chemical, physical, microbiological properties.
if these are kept the same then the medicine will be safe, efficient, and high quality
What does potency mean?
The amount of drug remaining in the medicine after storage
What is the meaning of ‘label claim’?
the percentage of the original drug content
What is an appropriate loss in medicine over shell life according BP?
10% -general
3% / 5% -when the degradation forms toxic products
What is temperature cycling?
medicine experiences temperature fluctuations due to movement from one storage condition to another
If the BP directs a preparation (special) to be ‘freshly prepared’ what does this mean?
Med must be made not more than 24 hours before it’s issued.
If the BP directs that a preperation (special) should be ‘recently made’ mean?
indicates that the prep is likely to deteriorate if stored longer than around 4 weeks 15-25 degrees C.
Describe how temperature promotes degredation?
- high temp = more likely chem degradation
due to more movement especially the drug - temp rise by 10 degrees C = 2 to 5 times increase in decay
- some antibiotic suspensions- heat catalyses rate of hydrolysis
Outline the major route of chemical degradation (hydrolysis)
hydrolysis- via nucleophilic addition elimination reaction e.g. ester + water = alchol + carboxylic acid
or solvolysis- same mech but different solvent
Describe formlation methods to stabilise drugs and reduce chemical degradation through hydrolysis
- Use a buffer to control pH
- Add a water miscible, less polar solvent (to form a cosolvent), unionised form less soluble in polar solvents
- contain the drug in cyclodextrins or miscelles
how does pH affect hydrolysis?
- hydrolysis catalysed by extremes of pH
- unionised form = most stable
- e.g. weak acid deprotonated is higher pH, low stability and higher solubility therefore more likely to hydrolyse
many drugs are weak acids or bases
how do cosolvent help to control stability?
- reduce pH extreme required for solubility - to favour more unionised in solution
- the cosolvent is less polar than water
- any degradation forms products which will not be as soluble in the cosolvent compared to water so foward reaction unfavourable
How docyclodextrins and micelles work?
- micelles are surfactants : drug is contained in the hydrophobic core where non-polar regions of the drug are attracted to non-polar hydrophobic regions
- cyclodextrins have a hydrophobc core due to the ring structure where the drug is contained
Name the types of oils used in emulsions
- Natural oils-triglycerides-injectables
- Mineral oils- derived from crude oil
- Volatiles oils-complex mixtures-plant oils used as flavours or aromas
What is caking?
when particles form larger aggregates in powder
Due to physical instabilities what are emulsions prone to? with emulsions?
- Creaming- the colalescence of droplets of oil which rise to the surface due to difference in density
- Cracking-complete phase sepeation
How to prevent creaming/cracking of an emulsion?
-shake bottle-liquid emulsion
- droplet size
- extreme changes in temp so don’t freeze
- type: o/w more stable than w/o
- emulsifiers (surfactants) around droplets
As emulsions are prone to oxidations and hydrolysis what is often needed to prevent this
Oil soluble antioxidants
Emulsions are microbiologically unstable so how could we stop this
Add a preservative- but it may disrupt the emulsifier film
adminstration routes of emulsions + uses
- oral- administer oils/oil soluble drugs
- topical-lotions or cream skin infections, inflammation, allergy
What are ointments?
greasy semi-solids with dispered powders which can be spread
Chemical instabilities with ointments
- sensitive to light and fat oxidation
common ingredients in ointments
- glycerides, paraffin-flammable, lanolin-allergic reactions
ads and disads of ointments
ads: occulsive-protective barrier and retains moisture
dry skin conditions, used in a bath, no preservatives, ppl with allergies
disads: very greasy, stains clothes,difficult to apply, patients don’t like
can’t use for wounds-microbial growth
What is autoxidation?
spontaneous reactions of a substance at ambient temp with oxygen- it is a free rad mech
How do you prevent oxidation?
- Antioxidants
- reducing agents
how can light sensitive products be packaged
- amber glass
- cardboards boxes
- aluminium foil
why are chelating agents used?
- to replace the water ligands and stabilise
if you can’t formulate without water and shelf life is inadequate then what do you do?
freeze dry- remove all the water from a frozen product under vaccum
What are the ads/disads of freeze drying
ADS: prevents hydrolysis and oxidation, porous solid is more easily dissolved
DISADS: more sensistive to moisture, expensive, slow, difficult for solutions containing non-aqueous (solvents other than water)
what do trace metals do?
catalyse oxidation
Some formulations are prone to decomp by oxidation in air. The air can be replaced by…
inert gases
How can drugs undergo hydrolyses when left out (tablets/left out )
gas adsorption- water vapour in air adsorb to drugs and excipients forming a thin water layer-hydrolysis can occur capillary condensation
common excipients in tablets
- Compression aids, binders
- lubricants
- Tablet coat
- Disintegrants
common excipients in powders
- Bulking agents
- anticaking agents
- Flow aids
- Flavours/colour
- granulating agents
- effervescent mixtures
- surfactants
Why are surfactants used in powders?
to improve dissolution
polysorbates
What are anticaking agents used for in powders?
to protect from moisture, absorbs water
silica
what are granulating agents ued for in powders?
bind powders into large aggregates of powders, drug + excipients
water soluble polymers: PVP, pregelled starch
What are effeverscent mixtures used for powders?
- produces CO2 for faster dissolution
bi/ carbonates, fruity acids
What are glidants/ flow aids used for in powders
better flowability
silica, magnesium stearate
What are some bulking agents in powders?
glucose, lactose, sorbitol,
starch, cellulose
What are flavours and colours for ?
Patient acceptability
What is geometric mixing
Mixing equal amounts of excipients with the drug, sequencially until it is made up to final weight-to uniform distribution
How do you prevent seperation of powders?
Equalise particle size via grind and sieve
Mix powders in same proportions-geometric
Granules
How are granules made?
Dry granulation:
Drug + excipient mix via geometric mixing
the dry powders are compressed by metal rollers
Wet granulation:
Powder mixture is wetted with a solution of polymer binder
Then sieve and dry them
Advantages of granules over powders
No separation of the powder particles
Better flow due to size
Features of soft capsules
Polymer coating
Filled with oils, liquids, semi-solids
Larger than capsules but easier to swallow
What are excipients in tablets?
- Compression aids, binders
- Lubricants
- Tablet coat
- Desintegrants
What do compression aids/binders do for tablets?
Bind particles under pressure tk make stronger tablets
E.g. cellulose
What do lubricants do in tablets?
Help make the tablet easier to eject from the machine after compression
E.g. Magnesium stearate
What 3 things does the tablet coating do ?
Protects-from water, air and O2
Identifies
Masks taste
E.g. polymers, sugars, colours, TiO2
What do desintegrants do for tablets?
Help to break up the tablet once in stomach or intestine, attracts water and swells up tablet
E.g. starch and cellulose
What are stabilisers used for in liquid meds?
To control pH
What are some common flavourings in liquid meds?
Oils, spirits/tinctures, conc water, waters, syrups
describe evaporation abd gas adsorption
evaporation: is the process of a liquid turning into a gas below its boiling point
gas adsorption: water vapour from the air adsorbs (forms weak bonds at surface- which can break -dissociate)
what is sublimation?
solid to gas at temp below the triple point of the substance
how can gas adsorption cause chemical degradation of a drug?
water v in atmosphere adsorb onto drug forming a thing water mono/multilayer.
some of the drug can dissolve in this layer
capillary condensation can also occur at pores on surface of the drug
what factors affect gas adsorption?
humidity and SA and surface energy (intermolcular forces)
what is a super saturated solution and what affects it?
when more than the max amount of solute is dissolved in solvent at a certain temperature.
temp increase increases solubility and cooling leads to supersaturation- preceptipation of crystals out of the solution
what is a polymorph and why is the most table used over the metastable form?
Polymorph- different patial arrangement of the same molecule
metastable form is very soluble but can convert to more stable form when inside the ody which can decrease bioavailability, ADME profile and plasma conc.
how can permeation occur through plastics and rubber?
Gases: water vapour, co2 and o2 in air cn escapse or enter through microscopic cracks and pinholes in lid, bottle or container
what are leachables and which packaging materials are most succeptible to them?
chemical substances which migrate from packaging into solution
rubber is most succeptible to leachables then plastics
what factors affect adsorption of drug to containers?
- drug conc
- pH (unionised form more likely to adsorb)
- lower Temp= more adsorption
- larger SA = more adsorption
