Flashcards in Biopharmaceutics Deck (57):
Bioavailability is concerned with ADME. True or false?
False - absorption only
What is absolute bioavailability?
The fraction of drug in the dosage form that arrives in the systemic circulation
IV administration is extra-vascular. True or false?
False - intravascular
There are transport proteins present in the epidermal cells of the skin to help with absorption of drugs. True or false
False - no transport proteins
the stratum corneum is made of living cells. True or false?
False - dead cells
There is no blood supply within the epidermis. True or false?
In which part of the skin are blood vessels found?
Only high molecular weight drugs can be used in transdermal drug delivery systems. True or false?
False - low molecular weight
Typically, how long does passage through the GIT take?
1 day - can vary based on eating, health etc.
Permeability in the mouth is less than in the skin. True or false?
False - greater than skin
Buccal and sublingual administration of drugs is good for hydrophilic drugs. True or false?
False - lipophilic drugs
First pass metabolism is avoided via buccal and sublingual administration. True or false?
The oesophagus is a significant site of absorption. True or false?
False - but is relevant to the mechanics of absorption
There are no transporters for nutrient absorption in the stomach. True or false?
When gastric emptying is slow, alcohol absorption is high. True or false?
False - alcohol absorption is slow
What are the two mechanisms of transport across the GI epithelium?
The transcellular route is preferred for small lipophilic molecules. True or false?
Drugs with a log P <0 cross via the transcellular route. True or false?
False - paracellular
Starting with disintegration, what are the steps that follow before a drug is absorbed?
Disintegration -> dissolution, permeation, pre-systemic metabolism
What are the two key competing processes to dissolution and permeation?
Transit and stability
In the BCS, a drug is considered to be highly soluble under what circumstances?
the highest dose strength is soluble in 250ml or less of aqueous media over the pH range 1-8
In the BCS, a drug is considered to be highly permeable under what circumstance?
When the extent of absorption in humans is expected to be more than 90% of the administered dose (predicted by lab methods)
Drugs in BCS class 3 have a high permeability but low solubility. True or false?
False - high solubility, low permeability
What are the limitations of the BCS system?
Doesn't take into account stability of drug e.g. at different pH values or the binding interactions with the gut or its contents
Name a drug that is under Class I of BCS
Name a drug that is in Class II of BCS
Name a drug that is in class III of BCS
Name a drug that is in class IV of BCS
Time to peak plasma concentration is related to the extent of absorption. True or false?
False - rate of absorption
What indicates the extent of absorption?
Area under curve
What is the equation for absolute bioavailability?
F = AUC(oral) / AUC (IV)
When F = 100, it shows 100% bioavailability. True or false?
False, F = 1
What is the difference between a drug and a medicine?
The drug is the API, pharmacological agent and therapeutic molecule whereas the medicine is the delivery system, drug + excipients and the formulation
Why does "available at the site of action" translate to "arrives to the systemic circulation"?
For practical reasons - blood can be sampled easily
PK reasons - drug is central compartment from which drug is distributed
Pharmaceutics - once drug is in the blood, formulation is irrelevant - drug is dissolved in blood plasma
What are the routes of administration across epithelial layers?
Buccal, gastric, rectal
How can the epithelial layer be bypassed?
Parenteral administration - intravascular or extravascular
What are the exceptions to absorption of drugs in the stomach?
No absorption takes place in the stomach normally as there are no transporters of absorption proteins to exploit however highly permeable drugs e.g. ethanol and weakly acidic drugs e.g. aspirin are able to be absorbed in the stomach
What is meant by bioequivalence?
No significant difference in AUC, Cmax and Tmax
What are biopharmaceutics?
They can be biologics - examples include monoclonal antibodies, ADC, interleukins, peptides and virus-like particles
What are the two ways in which biologics can be formulated as?
Liquids of lyophilised solids ready for reconstitution
What are the advantages of solid form biologics?
Dose and injection volume are adjustable
Can be developed as multi-use formulations
What are the advantages of luquid form biolog
More convenient to end user
Better patient compliance
What are the disadvantages associated with liquid form mabs?
Chemical degradation - hydrolysis
Physical stability more difficult to control - aggregation
Name some buffers that can be used in the formulation of proteins and mabs
Acetate, citrate, succinate, histinde
What are salt and tonicity modifiers used for in formulation of mabs and name a common one
Which type of mab injection requires an isotonic preparation?
Which type of mab injections are able to handle hypertonic or hypotonic conditions?
IM or SC
What is the role of surfactants in the formulation of mabs and proteins?
mAbs are flexible molecules with hydrophobic and hydrophilic regions - unfolding leads to aggregation - surfactants cover interfaces therefore limit unfolding
Why may antioxidants be needed in the formulation of proteins and mabs?
Because polysorbates (surfactants)
can oxidise over time which can affect shelf-life so antioxidants e.g. EDTA needed
Why are protein stabilisers needed in the formulation of proteins and mabs? Give an example of one
For preferential hydration of proteins. Stabilisers are preferentially excluded from the protein's surface - allowing hydration. E.g.s include sugars e.g. sucrose and amino acids e.g. arginine
What are the limitations of using sugars as protein stabilisers?
Disaccharides are susceptible to hydrolysis at low pH and sucrose hydrolyses to glucose and fructose at pH 5
Which amino acids are most susceptible to oxidation?
What is the limit for presence of aggregates set out by WHO?
less than 5%
Which IgG is more prone to aggregation than others?
What are leachables?
Compounds released form container closure system when in contact with solvent
What are extractables?
Subset of compounds eluting during normal storage or use conditions e.g. infusion bag