excipients Flashcards
what is mixing?
the randomisation of dissimilar particles within a system
what are the 3 most common difficulties in powder mixing?
homogenity is difficult to achieve
demixing can cause segregation
overmixing can degrade particles
give 3 parameters effecting effective mixing?
particle size, particle shape and density
name and describe 3 types of powder mixing?
convective: moving large groups of molecules from one part to another
diffusive: mixing individual particles
shear mixing: moving one layer over another
give 3 ideal excipient properties?
chemically stable, inert and cost effective
what is the role of binder and give and example?
adhesion of power particles, e.g pre gelatinised starch
what is the role of dilutent and give an example?
bulk out the drug to fill a capsule or make a tablet bigger, e.g cellulose
what is the role of disintegrant?
promotes the rapid break up of particles upon contact with water to give a larger surface area and improve the rate of dissolution
what is the role of glidant and give an example?
improves powder flow during processing, e.g talc
what are the 3 types of lactose and how are each of them produced?
lactose monohydrate, anhydrous lactose, spray dried lactose.
LM = crystallised from supersaturated lactose
AL = produced by drying, milling and sieving lactose solution
SDL = produced by spray drying lactose solution
what is pre gelatinised starch used for and how is it made?
can be used as a binder, Is made by rupturing granules at 62-72 degrees
what can powdered cellulose be used for?
filler, binder, disintegrant and binder
what is another form of cellulose, how is it made and what is it used for?
micro crystallised cellulose, made by acid hydrolysis, used as dilutent and binder in wet granulation
what can talc be used for?
glidant
name 2 excipients that are not suitable for children?
ethanol and propylene glycol
give two types of immediate release tablets?
disintegrating
chewable
give 3 excipients that aid processing of tablets?
lubricant, anti adherent, glidant
give 3 excipients that aid drug release and absorption?
disintegrant, dissolution enhancer, absorption enhancer
what is the role of anti adherent and an example?
prevent powder adhesion to the tablet punches e.g stearic acid
what are the 6 mechanisms of tablet disintegration?
1) swelling (water uptake)
2) wicking (creation of hydrophilic parts to draw in more water)
3) strain recovery (particles relax and then reform their shape, forcing others out of the way)
4) heat of interaction (heat energy is released forcing particles to expand)
5) interruption of bonding forces
6) repulsion (water uptake causes electrostatic repulsion)
give an example of a superdisintegrant?
sodium starch glycolate
what compounds are needed for effervescent disintegrant?
carbonate or bicarbonate
what are granules?
solid, dry aggregates of powder particles
give 3 pros and 2 cons of granules?
pros
- better handling
- less likely to segregate
- better compaction
cons
- additional processing steps
- instability during granulation
how are granules made?
aggregating powders with a binder
name 2 attractive forces that can hold granules together?
van der Waals
electrostatic
what is drying defined as?
the mass transfer of a volatile component out of a solid liquid mixture
why is a large surface area beneficial for drying?
causes effective heat and mass transfer
how do we go from a wet substance to an air dry substance, and from an air dry substance to a bone dry substance?
wet - air dry = remove the free moisture content
air dry - bone dry = remove the equilibrium water content
describe lipinskis rule of 5 in drug properties?
- no more than 5 hydrogen bond donors
- no more than 10 hydrogen bond acceptors
- molecular mass less than 500
- logP less than 5
what does a positive and negative pie value mean?
positive: more lipophilic than hydrogen
negative: less lipophilic than hydrogen
what does a positive and negative sigma σ value mean?
positive: electron withdrawing group
negative: electron donating group
describe what a perfect particle distribution curve would look like?
normal distribution where mean = median = mode
what is the mean median and mode order of a particle distribution curve with more larger particles than small?
mode over median over mean
what is the mean median and mode order of a particle distribution curve with more smaller particles than large?
mean over median over mode
how can particle size be reduced?
via cutting, compression or impact from different types of mills
what is primary and secondary packaging?
primary: In contact with the drug
secondary: not in contact with the drug
give 2 disadvantages of plastic packaging?
low chemical inertness
plastic components may leech into the drug
give 4 reasons why glass is a good choice of packaging?
inert
good barrier properties
stable at high temperatures
can see content inside
what are the 3 types of glass and what are they used for?
type 1: fluids for injection
type 2: aqueous properties
type 3: used for dispensary bottles
what is buccal delivery?
inside the cheek
what is sublingual delivery?
under the tongue
what are the layers in the mucosal lining of the mouth?
epithelial membrane, basement membrane, submucosa / lamina
what are the two types of epithelium?
non-keratinised: strechy e.g buccal and sublingual areas
keratinised: non strechy e.g gums and roof of the mouth
what is the average ph of saliva?
6.4
what are the two major routes of simple diffusion for a drug entering through the membrane?
intracellular: crossing the polar domain of the cell (lipid soluble)
intercellular: crossing through the aqueous spaces between cells (hydrophilic)
what are the 4 things that a buccal drug must contain to aid its function?
mucoadhesive agents
penetration enhancers
enzyme inhibitors
backing membrane
what is the ideal molecular size and log p of a buccal drug?
size: less than 500um
logP: 1.6-3.3
what is the ideal particle size for dry powder inhalers?
2-5um
how is micro ionisation of particles done and explain the process?
jet milling:
- material is fed into a grinding chamber and is introduced to high velocity air which causes the particles to knock into each other, finer particles can then leave the chamber with the air flow
what excipient is used to help particles flow through the airways?
lactose
explain how a DPI works?
hard gelatine capsules are placed into the device prior to use, the capsule is pierced at either side and air flow causes the powder to be dispersed
what is a pMDI inhaler?
a solid drug dissolved in a non polar propellant in a compressed gas canister
what liquified gas can be used as a propellent in pMDIs?
hydrofluoroalkanes
what are nebulisers?
when a drug is dissolved in a polar solvent and administered continuously / intermittently over a defined time, not requiring any coordination
give 3 rationale for tablet coating?
improve friability for handling
protect against oxygen water etc
improve ease of swallowing
where are immediate release tablets released?
stomach
where are delayed release tablets released?
intestine
what are extended release tablets?
release a large dose over a long time
give 2 characteristics of cellulose derivatives for immediate release tablets? and give an example?
lots of OH groups and low molecular weight, e.g methyl cellulose
give an example of a cellulose derivative for delayed release?
cellulose acetate
give 2 characteristics of cellulose derivatives for extended release tablets?
high molecular weight, hydrophobic alkyl substituents
give an example and a feature of a polymethacrylate for immediate release?
aminoalkylmethacrylate, water soluble in the stomach
give a feature of a polymethacrylate for delayed release?
insoluble in the stomach but soluble in the intestines, containing carboxyl groups
give a feature of a polymethacrylate for extended release?
water insoluble at any PH but swell in water
what type of release tablet is PVA used for?
immediate release
give 4 positive features of film coatings and 1 negative feature?
retains tablet shape, thin and matte, single step process, coating doesn’t add much weight
high cost
do sugar coatings alter tablet shape?
yes
give one pro and one con of sugar coatings?
pro: cheap and safe
con: adds a lot of weight
name the 6 steps of sugar coating?
sealing
subcoating
smoothing
colouring
polishing
printing
give 3 possible defects of film coated tablets?
orange peel effect (uneven)
cracking (insufficient coat strength)
peeling (bad adhesion between coat and tablet)
give 3 defects of sugar coatings?
rough, dull appearance, splitting
