Biopharmaceutics Flashcards
What is biopharmaceutics
Interaction of the biological system with the drug and the drug delivery system
Why do some routes besides intravenous administration not reach 100% bioavailability?
Not all drug present in the dosage form will reach the blood
Formula for bioavailability
F= area under curve (oral) / area under curve (iv)
What is disaggregation
Primary drug particles separate from other molecules
What if the primary drug particle is poorly water soluble?
Stays as a solid
Doesn’t get absorbed
Mucosal barriers
Separate the external environment from the body’s internal
Selectively permeable= impermeable to bacteria and toxins but permeable to water, ions and solutes
Eg= nasal mucosa , skin, lung, genital urine tract
What is apical and basolateral side
Apical= lumen
Basolateral= blood side
What are the 5 main ways of absorption across mucosal barriers
1) trans cellular = passive diffusion
2) trans cellular= active transport
3) paracellular= passive diffusion between cells
4) lipid absorption via micelles
5) particulate absorption via Gut associated lymphatic tissue
Passive trans cellular route
High concentration on apical side to low concentration inside the cell
What changes when logP increases
Solubility decreases
Plasma proteins binding increases
Binding to non target sites increases
What would happen to the rate of drug absorption across the intestine if you double the dose of a lipophilic drug
Rate would double
How does drug size affect absorption
Larger molecules cross cell membranes more slowly than smaller
Tight junctions restrict the diffusion of polar molecules
Passive paracellular route
Absorption through tight junctions
active transcellular route/ carrier mediated
molecule ‘piggybacks’ into the cell using a system designed for natural substrates such as amino acids and vitamins often against a conc gradient
lipid absorption via micelles/ bile salts
bile salts secreted into small intestine to emulsify lipid molecules
lipids are hydrolysed by lipases to give monoglycerides and fatty acids
formation of mixed micelles of mono glycerides, fatty acids and bile salts
lipidic molecules absorbed by partition from micelle into the cell
chylomicrons
complex mixed with lipoproteins and fats
vectors that carry lipids
particulate absorption via gut associated lymphatic tissue
endocytosis via membranous cells in the small intestine
absorption into the lymphatic system
eventual distribution to liver and spleen
BCS (class of drugs)
class1= high solubility, high permeability
class2= low solubility, high permeability
class3= high solubility, low permeability
class4= low solubility, low permeability
application of BCS
Good bcs?
class1= dissolve rapidly and rapidly absorbed across gut, good bioavailability
class2= dissolution rate is likely to limit absorption
class3= dissolve rapidly but poorly permeable
class4= very poor bioavailability, oral route may be impossible
1+3
bioequivalence
rate and extent of absorption is the same after administration of the same molar dose
Ficks law
Passive diffusion from high conc to lower conc when conc is linearly proportional
Why is there a negative sign in ficks first law
Molecules sometimes move from high concentration to low concentration
PSA
Polar surface area
What does a higher logP mean
Hydrophobic
What is EDTA
Chelating agent
Binds Ca2+ ions
Why is more hydrophobic molecules administered orally
Effectively absorbed
More chances of getting a bio waver
Highest dose dissolved
Bioavailability above 85%
Why do you want a biowaver
Reduce costs
