Biopharmaceutics Flashcards
What is biopharmaceutics? Why is it useful?
what happens to a dosage form up until the drug is absorbed into systemic circulation
- solubility, dissolution and permeability
it determines the amount of active pharmaceutical ingredient reaching systemic circulation
What does biopharmaceutics influence?
efficacy
toxicity/side effects
duration of action
What is MEC?
What is MSC?
MEC - minimum effective concentration
it is the minimum concentration that is required for the drug to exert its effects
MSC - maximum safe concentration/minimum toxic concentration
it is the highest concentration that a drug can reach before having toxic effects
What are the three main areas for drug delivery in the GIT?
How does transit time change across the GIT?
stomach, jejunum (small intestine- primary site of absorption), large intestine
transit time increases as you go across the GIT
- shortest at the stomach (5min-2hr), intermediate in the small intestine (3-5hr) and longest at the large intestine (12-24hr)
What are the function of mucus in the GIT?
a mucous layer covers the GI mucosal membrane
protects the mucosal membrane from physical damage
acts as a diffusion barrier and regulates water movement
lubricates the GIT
binds bacteria
holds immunoglobulins (antibodies) so they can act on pathogens
How is erosion and damage of the mucosal layer overcome?
the mucosal layer is continuously eroding and suffering mechanical damage
continual replacement of mucus overcomes this as there is constant repair and replacement
- produced by rapidly overturning epithelial cells
What is mucus made up of?
lipids and glycoproteins (mucins), mineral salts free proteins and water (majority)
mucins are made up of
- 80% carbohydrates = N-acetylgalactosamine
- 20% protein core = glycosylated region (serine, threonine and proline), amino and carboxyl regions that are high in cysteine
Why are the cysteines in mucin useful?
cysteines form disulphide bridges resulting in a viscous gel
- protective
cysteines are potential targets of muco-adhesive agents
- agents that stick to the mucous membrane
What is the purpose of the stomach?
to reduce solids into uniform consistency
- creating a paste called chyme that passes to the small intestine
= increases surface area of digested food
= increased contact time of ingested material with the mucous membrane
enables absorption
Why is transit time in a fasted and fed stomach different?
pH of the stomach may rise after a large meal (may rise as high as 7)
- due to proteins which can act as a buffer
large meals may be difficult to break down and can have longer transit times
How are drugs absorbed?
weakly basic drugs are more likely to be absorbed in alkaline environments
- remain unionised and are able to diffuse through a lipid cellular membrane
theoretically weakly acid drugs should be primarily absorbed in acidic environments
drugs are also more likely to be absorbed if they contain lipophilic groups
Why is the surface area of the small intestine large?
main absorption site (jejunum)
has
- folds of kerckring (folds in the submucosa)
- villi (finger-like projections)
- microvilli (found on each villi)
What are the four main routes of absorption in the GIT?
paracellular - transfer of substances across an epithelium by passing through the intercellular space between the cells
= only small hydrophilic molecules can cross
transcellular - transportation of solutes by a cell through a cell
passive diffusion - must be a hydrophobic molecule
carrier mediated (active or facilitated) - proteins bound in the membrane aid transport of molecules across the lipid bilayer
endocytosis - phagocytosis or pinocytosis (uptake of liquid via vesicles)
Why is the stomach a poor absorption site?
the stomach is a poor absorption site due to its thick mucus layer and small surface area
- is more of a storage organ
