Drug Stability FULL

what is drug stability

the capacity of a drug to remain within established specifications of identiy for a specified time

what problems arise due to instablity

• loss of drug through chemical reaction

• loss of efficacy

• poor bioavaliability

what is shelf life

time taken to reduce concentration of drig to 90% of original value

what type of drug form can lose activity

liquid and solid

types of physical instability

• volatility

• uptake or loss of solvent

• polymorphusim

• denaturation

chemical instability examples

• hydrolysis

• oxidation

• elimination

• racemisation + isomerisatiomn

what factors affecr hydrolysis

• ph

• temperature

• solvent

• structure

what dosage forms does pH affect

liquid and solid form

what can the pH rate profile be affected by in liquid doses

buffers

how can you activate the carbonyl carbon for nucleophilic attack by the water molecule

protonation

what is the process called when reversing acid hydrolysis

esterification

what can make a good leaving group

alcohol

what does an increase in temprature do in regards to the hydrolysis rate

increases it

why are stability studies carried out at high tempratures 60-80 celcius

as the hydrolysis rate can be measured more easily

how can you measure the hydrolysis rate

using the arrhenius equation

what is the arrhenius equation

what should you do if a particular drug formulation is unstable at room temprature

label with storage instructions

what is a complication of using the arrhenius equation for solid forms

• melts on temprature release

• changing of polymorphic form

• loosley bound to water which is lost at a higher temprature.

equation to predict the effect of solvent on hydrolysis rate

dielecctric constant and ionic strength

what does greater electronegativity lead to in terms of polarisation

increased polarisation

why do esters hydrolyse more readily than amides

as oxygen is more electronegative than nitrogen

what can infulence the rate of hydrolysis

inductive and mesomeric effects

what shape is the transistion state

tetrahedral

what may bulky groups do to the hydrolysable group

block or shield it from attack

what is tafts steric factor a measure of

steric effect

what are hydrolysis rates measured under

acidic and basic conditions

what factors are measured under basic conditions

steric and electronic factors

what factors are measured under acidic conditions

only steric factors

how can you protect against hydrolysis

solubilising in surfactants

how can oxative degregation occur

by autoxidation

what is autoxidation

a slow irreversible oxidation in the presence of atmospheric 02

what are the 3 chain processes of autoxidation

initiation propagation and termination including free radicals

what can autoxidation be catalysed by

light and trace metals

what are the factors affecting autoxidation

• light

• sensitizers

• catalysts

• hydrogen ion concentration

• temprature

how does light affect autoxidation

the energy achived from a light source is capable of forming radical species

how do sensitizers affect autoxidation

upon recieving energy from another molecule they become excited and release light

how does temprature affect autoxidation

generally the rate increases with increasing temprature

how does pH affect autoxidation

by lowering it, it slows it down

what are free radicals?

species with one unpaired electron in their outer shell

what is a heterolytic bond cleavage

both electrons making up the bond move together when the bond is broken

what is homolytic bond cleavage

when the two electrons making up the bond gets distributed equally between the two atoms so each atom gets one electron

what is an enantiomer

they rotate the plane of polarised light by an equal amount in opposite direction

whats an equal mixture of enantiomers called

racemate

how can structures be chiral

if they cannot be superimposed on their mirror image

what is a chiral centre

when a molecule contains a carbon atom containing 4 different groups it will not have a plane of symmetry

how to create a 50:50 mixture of enantiomers using racemisation

inversion of stereochemistry at a chiral centre

a change at one chiral centre gives rise to what

diastereomers

whats the difference between optically active and optically inactive enantiomers

idk there is a Hydrogen bond near the OH bond when its optically active

when does inversion at a chiral centre occur

when the centre is adjecent to a carbonyl group