Biopharmaceutics Flashcards
What is biopharmaceutics a study of?
Biopharmaceutics is a study of factors affecting the rate and extent of absorption - problems which formulation must overcome to maximise effiicacy of drug of drug
- these factors ultimately dtermine how fast and how much drug will be available in the drug.
whatb is bioavailability proportional to?
Bioavailability is proportional to the plasma drug concentration
Which factors affect Bioavailability?
Physiological factors
-surface area of absorption
-pH of GI fluids
-liver metabolism
Physiochemical factors
-sollubility and dissolution
-lipid solubility and log P
-molecular weight
Exipients
-Lubricant
-surfactant
-viscosity enhancer
Dosage form:
-aqeuous solution
-aqeous suspension
-coated tablet
How does the surface area of the GI track affect absorption
On the wall of the small intestine are villi and on those villi are microvilli which vastly increase the surface area of the GI track, this is why the vast majority of drug absorption occurs in the small intestines.
How to maximise bioavailability before it reaches the small intestines?
Ensure it does not get degraded in the stomach, by pH degredation for example, intracoating on the forulation can stop the drug being effected by the stomach and remain intact.
What is gastric residence time
The amount of time the dosage form remains in the stomach
Which dosage form ha a smaller gastric residence time and reaches the small intestines quicker
solid dosage forms remain in the stomach for longer however liquid dosage forms will pass through the stomach quicker.
How does diet effect bioavailabilty
Diet will have an effect on how long the dosage form remains in thew stomach. Eg. taking medication before eating will allow the medicine to bypass the stomach quicker then after eating food.
How does lvier (first-pass) metabolism effect bioavailability?
Depending on the structure of the dryg the may act as a substrate for liver enzymes which will then degrade the drug and massively redcue the bioavailability. Oral medication will always go through the liver metabolism.
Taking the medication with food could occupy the liver enzymes remaining they wont entriely be able to degrade the dosage form.
How does dissolution effect bioavailability?
Due to interfacial tension between the drug particle and the liquid it is in, a diffusion layer forms around the outside. the drug particle must be wetted dissolve and pass across diffusion layer before it can be absorbed by the GI track.
-the higher the interfacial tension, the less easier the drug is wetted and therfore the harder it is for the fluid to absorb the drug.
-using a surfactant can help with this by acting at the interface between the solid and liquid to reduce the interfcial tension and improve the wetting/dissolution of the drug.
Noyes-Whitney equation - will increasing or decreasing facrots increase or decrsse the dissolution rate
Increase dissolution rate:
-increase diffusion coefficient (D)
-increase surface area (A)
-increase saturation solubility in diffusion layer (Cs)
Decrease diffusion rate:
-increase drug concentration in GI fluid (C)
-increase the thickness of diffusion layer (h)
Noyes-Whitney equarion
dC/dt = DA(Cs - C) / h
D - diffusion coefficient
A - surface area
Cs - saturation solubility in the diffusion layer
C - drug concentration in GI fluid
h - thickness of diffusion layer
pKa / pH effect on bioavailability
Knowing the pKa of a weak acid/bases allows you to predict the ionisation which allows you to predict the dissultion
Weak acids
-as the pH increases, and goes above the pKa they become more ionised, and dissolution increases
Weak bases:
-as pH increases above pKa, Ionisation decreases, dissolution decreases
How to overcome pH sollubility of weak electrolytes
Formulate weak acids as salts
-this will result in the weak acid having a positive charge which has a buffering effect on the diffusion layer, increasing the pH of the diffusion layer and therefore increasing the ionisation and increasing the diffusion layer. after breaking out of the diffusion layer they will revert back to their original form as smaller particles which will allow a larger surface area and therefore increased dissolution rate.
Formulate weak bases as salts -
How does Log P effect bioavailability
Log P gives an understanding of how lipid soluble a drug is.
-if Log P is too high or low bioavailability is poor
-ideal Log P - 2-4.5
How does molecular weigh effect bioavailability
the larger the molecular weigh the poorer the absorption
-ideal Molecular weight - <500g/mol
What transport mechanisms make up the transcellular pathway
Passive diffusion - drug passes from a region of high conc. to low conc. across a concentration gradient
carrier mediated - transporter molecule carries the drug across the cell membrane
transcytosis -
ion pairing - .
pore transport
Passive diffusion
Lipid soluble drugs are more easily absorpbed through membranes than water soluble drugs
ie. High Log P are much more easily absorbed than lower Log P drugs
-Determined by physicochemical properties of drug:
ie. Log P, nature of the membrane and concentration gradient
Passive diffusion decreases over time, as the concentration of drug in GI fluid decreases
Stages of passive diffusion
-Drug in solution in GI fluid
-Passes across the gut wall into solution across the concentration gradient.
-then carried away by blood circulation into liver
-Higher drug concentration in GI fluid, Lower drug concentration in blood, due to volume of blood the drug is being carried in.
Ficks first Law - passive diffusion
dm/dt = PCg
P-permeability constant
Cg - conc. of drug in GI fluid
Drug permeability across GI for passive diffusion is determined by fick’s first law
increase in drug concentration in GI fluid increases rate of absorption of drug
Carrier-mediated transport vs passive diffusion
Passive diffusion decreases over time, as the concentration of drug in GI fluid decreases
Carrier mediated transport is specific and energy dependent and against a concentration gradient
What is the purpose of formulation
Patient - provides dosage form to maximum patient compliance
Drug properties/physiology - maximise stability, solubility, permeability
Disease - maximise efficacy of drug by ensuring drug reaches site of action
How does different dosage forms effect bioavailanility
The dosage form effects bioavailability as certaiin dosage forms take up an increased number of steps before they get dissolved, the multiple steps in this proccess can cause the drug to be less and less bioavailable.
-the quicker the drug passes through GI fluid and into the blood stream the greater the bioavailability.
which dosage forms have the greatest bioavailability?
1.Aqeous solution
2.Aqeous suspension
3.capsules
4.uncoated tablets
5.coated tablets
