EXAM 2 L1 Flashcards
Bioavailability definition
Refers to the rate and extent of drug absorption
Absolute Bioavailability
the AUC of a given dosage form compared with the AUC of the same dose injected intravenously
Relative Bioavailability
Refers to the AUC of a given dosage form compared to an arbitrary reference standard
Bioequivalent does not mean…
The therapeutic effect of two dosage forms are equivalent
Most important factor in pharma and toxicology
Dose-response relationship
Dose covers two aspects:
The amount of chemical in which the whole organism is treated
The local concentration of the chemical at the biological response site
T/F: relationship between dose and receptor concentration is a function of the ADME
True
Three levels of dose response
Toxic Response
Safe and Efficacious
Not Efficacious
Processes required for oral absorption if Monolithic dosage forms
dissolve to saturated solution
dissolved - diffuse from the area of high to low conc.
Molecules diffuse through the bulk solution
Replenishment of drug molecules in the diffusion layer is achieved by further dissolution
T/F: Surface area increases when solids are broken up into smaller pieces
True
Rate of Dissolution equation
(dM/dt)
Rate of dissolution definition
The change in the amount of mass that appears in solution over time
Rate of dissolution dependent on…
D-Diffusion Coefficient (Fick’s 1st)
S- surface area of tablet/granules available to donate drug to solution
h-thickness of stationary layer
Cd-concentration of drug in the donor (X=0)
Ca-Concentration of drug in bulk solution (x=h)
Noyes-Whitney equation
(dM)/(dt )= (DS)/(h)(Cd-Ca)
Dissolution rate is proportional to…
D (diffusion)
Tablet/particle surface area
Difference in the concentration gradient
T/F: Dissolution rate is inversely proportional to h
True
Permeability vs dissolution
Permeability - diffusion across a barrier (cell membrane) instead of across an unstirred layer
Permeability needs to include
Partition coefficient K to account for changes in environment between inside and outside barrier (water vs hydrophobic core of membrane)
Permeability abbrev.
D = Diffusivity
S = Surface area of the boundary (GI surface area)
K = Partition Coefficient
Cd = Donor (GI) concentration
h= thickness of barrier (thickness of GI cell membrane)
P = (DK)/h=permeability
3 factors can limit the ability of a drug to absorb after oral administration
Solubility
Dissolution
Permeability
Limited Solubility effects
represented as a small Cd value in previous equations
Dosage form dissolves fast and drug permeates readily
Increasing dose doesn’t increase blood levels as the GI fluids are already saturated
Limited Dissolution effects
Drug is unable to dissolve into the solution from the dosage form in sub-saturated fluid
Dissolution time is greater than the time for absorption in the intestines
Often due to poor formulation/manufacturing
Need to have a tablet that can dissolve but also stand up to shipping and handling
Limited permeability effects
Characteristic of the API itself similar to solubility limited
Dissolution is fast with sub-saturated fluids
Increasing the amount of drug increases absorption
See notes up to now and previous slide with permeability equation
Definition of generic drug
A drug product that is comparable to a brand/reference listed drug product in dosage form, strength, route of administration, quality and performance characteristics, and intended use
Therapeutic equivalence two factors
Pharmaceutical equivalence
bioequivalence
Cmax definition
The max blood/plasma concentration from a dosage form
Tmax definition
Time to reach the max blood/plasma concentration from a dosage form
AUC
Area under the curve
