dds product stability

why are drugs rarely administered as pure chemical subs

• they dh suitable characteristics to have therapeutic outcome

• so they are usually formulated w other excipients to form preparation

why is drug stability important

• to ensure chemical and physical integrity of the drug formulation dur the shelf life of product

• shelf life shld be at least 3 years, no less than 95% potency

drug stability classification (4)

1. stable al conditions —> kaolin

2. stable if handled correctly —> aspirin

3. moderately unstable with special handling —> vitamin

4. very unstable —> antibiotic sol

what is a product?

a formulated pharmaceutical product

considerations of product stability (3)

1. chemical stability

2. excipient stability

3. packaging options

guidelines (3)

1. shelf life at least 3 years

2. potency 95% and up, under reco storage conditions

3. look & perform as it did when first manufactured

order of reaction

1. rate of degradation

• depend on number & conc of reactant

2. how to express it

• T50 —> time for conc to be halved, determine dose freq, tiem to take effect & potential risks

• T95 —> time where 5% loss of drug conc

what can drug degradation be due to (4)

1. heat

2. oxygen

3. light

4. moisture

degradation processes (4)

1. trace metal catalysis

2. oxidation

3. photolysis

4. hydrolysis

effect of temperature

• affects all 4 degradation processes

• 10degree inc = decay inc by 2-5 folds

• Arrhenius eqn to show rs between temp & rate of degradation, can be used to calc how much drug degrades dur accelerated stability testing

hydrolysis

• most common degradation process

• chemical breakdown of molecules with water

• can happen even in digestion for breakdown of nutrients for easier absorption

• water acts as a catalyst for degradation

• solvolysis = chemical breakdown of molecules using a solvent

conditions that catalyse hydrolysis (3)

1. presence of OH-, H30+

2. heat & light

3. high drug conc

how to prevent breakdown

modify chemical structure to make it less susceptible to hydrolysis

oxidation

• loss of electrons to gain oxygen

contributing factors (3)

1. light

2. trace metals

3. oxygen & oxidising agents

how to prevent breakdown

1. add antioxidants

photolysis

• can contribute to other degradation processes

• chemical breakdown of molecules with light

• shorter radiation wavelength (UV light) = higher molecular energy = degradation

what causes increase in energy (4)

1. decomposition of molecules

2. conversion of light to heat energy

3. retention/ transfer of energy

4. light emission at new wavelength (fluorescence)

solution to prevent inc in energy

• opaque & inert packaging

• amber bottles/ aluminium foil/ blisters

trace metal catalysis

• trace metal is absorbed by drug and acts as a catalyst for degradation

• happens when drug comes into ctc dur manufacturing, shipping, storage

how to prevent breakdown

add chelating agent to cut off metal compounds

hygroscopicity

• absorption of moisture and drug dissolves itself

• depends on relative humidity

• hygroscopic formulates need to be manufactured & stored @ low humidity

how to prevent hygroscopicity (2)

• use impermeable packaging —> glass bottle/ foil blisters

• add desiccant to packaging

info req before pre clinical research (3)

1. expiry date

2. storage conditions

3. stability data

info req for product registration

• stability data for 3 production batches stored for stated shelf life

types of testing before clinical research (2)

1. accelerated

• min 6mnths

• product placed under harsher conditions over shorter period of time

• obtain result quicker

2. long term

• min 12mnths

• product placed under milder conditions over longer period of time

• obtain result slower

post marketing safety monitoring

• still req aft HSA authorize product for marketing

• verify prod quality dur normal consumer use

• laborious but every step needed for patient safety