Stability and stability testing of pharmaceuticals Flashcards
How is quality measured?
- By the content of the active substance in the product
- By the purity of active substance in the product
- By the physico-chemical properties of the product
- By the microbiological properties of the product
- By the organoleptic and aesthetic properties of the product
What is hydrolyxis frequently catalized by?
-By hydrogen ions or hydroxyl ions and by acidic or basic species (buffers)
Give examples of the main classes of drugs that susceptible to hydrolysis?
“Known as labile carbonyls”
- Esters e.g aspirin , cocaine
- Amides e.g Dibucaine
- Lactones e.g Pilocarpine
- Lactams e.g Penicillins, nitrazepam
How do we prevent or reduce hydrolysis?
- Minimise contact - removal of moisture (water, humidity)
- Control manufacturing envrionement
- Introduce solid dosage form
- Adjust pH - reduces acid base catalysed hydrolysis
- Reduce solubility - if drug is not in solution it cannot be hydrolysed
- Form complexes
What is the main cause of drug degradation?
Oxidation
What is drug degradation influenced by?
Light and heat
What functional groups are prone to oxidation?
- Phenols
- Ethers
- Thiols
- carboxylic acids
- Aldehydes
- Catechols
- Thioethers
What is chemical oxidation?
It is the removal or the addition of an electropositive or an electronegative atom, radical or electron.
Oxidation is essentially the loss of electrons without th addition of oxygen. TRUE OR FALSE?
TRUE
What are free radicals?
They are chemicals containing alteast one unpaired electron
Free radicals are highyl unstable and highly reactive, TRUE OR FALSE?
TRUE
What is auto-oxidation?
It is the spontaneous oxidation of a compound in air or in the presence of oxygen.
Many pharmaceutical oxidations are irreversible chain reactions proceeding slowly under the influence of atmospheric oxygen. TRUE OR FALSE?
TRUE
Oxidation reactions over does not occur several years. TRUE OR FALSE?
FALSE
The shelf life is dependent on the suitability of the dosage form. TRUE OR FALSE?
TRUE
Oxidation involves the formation of free radicals. TRUE OR FALSE?
TRUE
What are the three steps in the chain reaction during an oxidation reaction?
- Initiation
- Propagation
- Termination
What occurs during the initiation reaction?
-Free radicals formed by the action of light, heat or trace of metals (such as iron - which comes form the formulation itself)
What occurs during propagation reaction?
- Formation of peroxy radical
- Removal of H from organic molecule to form hydroperoxide and a new free radical.
Propagation step is the chain reaction step. TRUE OR FALSE?
TRUE
What occurs in the termination step?
-Free radicals combine to form inactive (new) product
How do antioxidants work?
-They interrupt propagation by interaction with free radicals; which leads to the formation of an antioxidatant free radicals which is not sufficiently reactive to maintain the chain reaction.
How do we prevent or reduce oxidation?
- Precautions during manufacture
- Avoid contact of drug with heavy metals ions
- Replace oxygen in container with nitrogen
- Well filled containers less room for oxygen
- Store at reduced temperatures
What are the formulaton approaches of reducing and or preventing oxidation?
- Use antioxidants
- Use chelating agents e.g EDTA
- Adjust pH
What do primary antioxidants do?
-They interfere with propagation step
What do synergists do?
-They promote activity of primary antioxidants
Reducing agents have a lower redox potential than the drug, so are therefore more likely to be oxidised than the drug. TRUE OR FALSE?
TRUE
Decreasing pH often increases REDOX potential. TRUE OR FALSE?
TRUE
What is REDOX potential?
-The tendency of a chemical to acquire electrons and therefore be reduced and increases resistance to oxidation
The higher the REDOX potential to more likely to be reduced. TRUE OR FALSE?
TRUE
In adrenaline solution, decreasing the pH from 6 to 4 results in a 2 fold increase in chemcal stability. TRUE OR FALSE?
TRUE
Give examples of commonly used antixidants?
- Gallic acid
- Butylated hydroxyanisole
- Butylated hydroxytoluene
- Tocopherols
What photochemical degradation (photolysis)?
-The seperation or degradation of a molecule by the action of light
What occurs during photolysis?
- Molecules exposed to electromagnetic radiation, absorb light at characteristic wavelengths, causing an increase in energy state of the compound that can lead to:
- Decomposition
- Conversion to heat
- Emission of light at a new wavelength
What does photolysis result in?
- A change of colour in product
- Fading of colouring agents
How do we prevent or reduce Photochemical degradation?
- Storage and packages - amber bottles/boxes
- Darkness
- Store at cool temperatures
- UV absorbers
How do UV absorbers work and provide an example?
-They absorb harmful light radiation and dissipate the energy as heat of flourescence or in a reversible chemical reaction. e.g benzophenones
What is isomerisation?
Conversion of a drug to its optical or geometric isomer
What is an epimerisation?
-An epimer is one of a pair of stereoisomers. The two isomers differ in configuration at only one stereogenic center
What is polymerisation and provide a drug example?
-The process by which two or more identical molecules form a complex e.g ampicillin
What is dehydration and provide an?
-The breaking of a covalent bond to eliminate a water molecule from the structure e.g tetracycline
What is decarboxylation and provide an example?
-The elimination of carbon dioxide from a compound e.g when parenteral solutions of sodium bicarbonate are autoclaved
What are chemical incompatibilities?
When two chemicals rae mixed in a formulation and react, which is usually seen by precipitation from a solution
Provide example of physical degradations for tablets and capsules?
- Dissoultion rate
- Appearance
- Odour
- Friability - durability of drug during transit
- Hardness
Provide example of physical degradations for ointments and creams?
- Appearance
- Odour
- Viscosity
- Particle size distribution
Provide example of physical degradations for transdermal patches?
- Appearance
- Rate of drug release
- Adhesive strength
Provide some examples of forms of physical instability?
- Loss of water
- Change in product colour
- Change in product odour
- Crystal growth
- Polymorphic changes
- Caking of suspensions
How can physical instability be prevented?
- Formulation
- Manufacture
- Packaging
- Storage
