Stability Flashcards
what is stability
he extent to which a dosage form retains, within specific limits, and throughout its period of storage and use (i.e. its shelf life) the same properties and characteristics that is possessed at the time of its manufacture
what factors affect drug stabiltiy
- Environmental factors:
- temperature,
- light,
- humidity
- oxygen
- carbon dioxide
- Dosage form factors:
- particle size
- pH
- solvent system composition
- compatibility of anions and cation
- primary container
- additives
- molecular binding
- diffusion of drugs and excipients.
why be concerned about stabilty
- need to ensure patient receives the intended drug and dose
*Degradation will decrease concentration of API in the product
- prevent the appearance of contaminants or toxic compounds
*Toxic compounds can result from the degradation of either APIs or excipients
- exclude any decrease in bioavailability as a result of chemical or physical changes in the product
*Decrease in bioavailability will lower therapeutic effect
- To eliminate possibility of poor patient compliance as a result of substantial changes in appearance of product
what is shelf life
The period of time which if stored correctly the productis expected
to retain acceptable chemical, physical, and microbiological stability
expiry date
The date given on the product packaging which represents the end of the shelf life
– Expressed as month/year on packaging
• i.e NOV 18 – expires November 30, 2018
Expiration condition
On the day of expiry drug must still retain 90% of its labeled potency
* for dry products, reconstitue at time of dispensing: exp date req for both the reconstituted and the dry prouct
what are the types of tabiltiy
- PHysical
- viscosity, appearance, odor, colour suspendabiltiy
- chemical
- pH, drug content
- microbiological
- sterility, microbial load, preservative effectiveness
- Therapeutic
- activty and potency
- Toxicological
- identification of degradetion products
factors of physical stabiltiy -> what to look for
- all liq products
- sorption to drug container
- shedding of paritcles from glass containers
- evaporation of chloroform used as presevative
- solutions
- precipitation of drug or degredation products
- Suspensions
- caking of sediment
- particle growth
- Emulsions and screams
- creaming and cracking
- rediction in viscosity
- Ointments
- separation of liquid onto surface (bleeding)
- Solid dose forms
- phymorphic change
- change in disintegration time of dosage form
- chang in crushing strenght
- Transdermal patched
- change in drug release rate and adhesive characteristics
- inhalation and nasal aerosols
- change in particle size dsit and emitted dose
what is the primary evidence os instabiltiy of capsules
hardening or softening
what is the primary evidence os instabiltiy of tablets
powdering, chipping, mottling, discoloration and fusion
what is the primary evidence os instabiltiy of powders
Caking ,colorchange, swelling due to pre mature effervescent reaction
what is the primary evidence os instabiltiy of lozenges/troches
clumping, tackiness and dsiocoloration
evidence of instabiltiy for solutions in general
clarity, precipitation mmold/bacterial growth, odor and loss of volume
evidence of instabiltiy for emulsions
- odor, colour change, creaming, coalescence, phase separation and mold/bacterial growth
how can you enhance the stabilityof emulsions
- dec droplet size (deal is < 5um)
- obtain optimal ratio of water (40-60% of product volume)
- inc viscity of external phase
evidence of instablilty for suspensions
non uniformity, caking, crystlal grwoth (precipitation), easy of resuspension, mold/bac growth, odor, loss of vol
*less susceptible to chme degredation than solutions
vidence for instbaility for creams, grals and ointments (semisolid dosage forms)
Shrinking due to water evaporation, separation, discoloration,
microbial growth, grittiness.
vidence for instbaility for suppositories
Glycerin and PEG suppositories are hygroscopic – protect from moisture
• Softening, crystallization (polymorphism), dry out and harden
responsibilities of the pahrmacist for storage
- dispense older stock first
- sotre at rec conditions
- observe for evidence of isntabiltiy
- properly treat and lable products that are repackaged, diluted or mixed with other products
- dispense in proper container-closure system
- informa nd educate patients concerning proper stoage and use products including how to dispose of exp products
what is the aim for mircobiological stability
To prevent the presence and growth of pathogenic microorganisms which can spoil product
what are the souces for microbiological contamination and means to rpevent
- raw materials including water
- Manufacturing environment (atmosphere, equipment and work surfaces)
– Manufacturing Personnel
*prevent by sterilizationa nd addition of preservatives
ranges allowed for chemical stability
* Chemical degradation is often the most critical parameter determining shelf-life
- drug content of 90% of the theoretical value is considered themaximum allowable reduction
how can you combat the degredation fo chemcial products
overage
- ie make 110% conc
*only possible where degredation products are non toxic and dose is not critical
what are the types of degredation reactions
– Hydrolysis
– Oxidation
– Isomerization
– Polymerization
– Photodegradation
– Chemical incompatibilities
what chemcial groups are suspectible to hydrolysis
esters, amides, alctams and lactones
what factors affect hydrolysis
pH, buffer salts, ionic strength, presence of co- solvents, complexing agents, surfactants.
- beta lactam ring and opens up
- amide group on lidocaine hydrolyses and forms active
pH and degredation
diff drugs stable at diff pHs
a) stable at acidic pH, b) at basic, c) stable at neutral
what is oxidation?
what are the diff types of reaction
- free radical chain reactions
- initation is the fow step, so waht to inhibit that step or inhibit proporgation
- Initiation:
- X• + RH —> R• + XH
- Propagation:
- R• + O2 –> ROO•
- ROO• + RH —> ROOH + R•
- Termination:
- ROO• + ROO• —> stable product
- ROO• + R• –> stable product
- R• + R• –> stable product
oxidation examples
what factors can promote oxidation
free readicadicals -> light or heavy metals
isomerization
- many drugs depend on their isomer for activity
- must watch for racimization and epimerization
- important steroisomers are:
- > Geometrical isomers (naftifine)
- > strucutral isomers; betamethasone 17-valerate to betamethasone 21-valerate
POLYMERIZATION
alos type of dimerization
what is photodecomposition
photolysis
what facotrs affect stabilization of pharmacetuics
temperature,
solvent
, acid base catalyiss
light
oxygen
how to regulate affect of temp of stabiltiy
store product in refridgerator
how to regulate affect of solvent of stabiltiy
- replace aq solvent with a non aqueous
- solid dosage forms are usually not stable -> sue dry powder for reconstitution suspensions
how to regulate effect of acid base catalysis for stabilization of pharmaceuticals
– Control drug’s pH of maximal stability
– Use buffers
– Complexation with excipients (e.g cyclodextrins)
how to regulate the effect of light on stabilization of pharmaceuticals
use containers to protect from light
how to regualte efefcts of oxygen on stabilization of pharmaceuticals
- Reduce size of containers, use single-use
– Adding antioxidants: ascorbic acid, BHA, vitamin E
– Add chelating agents (EDTA) or citric acid
– Sealing container with inert gas e.g. N2
