IVIVC Flashcards
Innovator = ?
Brand (ex. Advil)
Describe bioavailability studies
- need to do Ba for every optimized formulation (past)
- ensure that the optimized “new formulation” is similar to the “old formulation” of the same drug
- lengthy and costly
In vitro = ?
within the glass
In vivo = ?
within the living
What the concept between IVIVC?
based on developing a relationship between dissolution and bioavailability
*a predictive mathematical model describing the relationship between an in vitro property of a dosage form and relevant in vivo response
In vitro property is ?
the rate of drug dissolution or release
In vivo response is ?
the plasma drug concentration or amount of drug absorbed (bioavailability)
Why was IVIVC developed?
To minimize the need for additional bioavailability studies as part of the formulation design
What is the difference between solubility and dissolution?
Solubility: the number of mg that can be dissolved in a certain volume (mg/mL)
Dissolution: the rate at which the mg dissolve into the certain volume (mg/time)
Noyes-Whitney Equation:
What does D stand for?
diffusion coefficient (diffusivity) of the drug
Noyes-Whitney Equation:
What does the S stand for?
surface area of the drug
Noyes-Whitney Equation:
What does the h stand for?
thickness of the diffusion layer liquid film
Noyes-Whitney Equation:
What does the Cs stand for?
saturation solubility of the drug
Noyes-Whitney Equation:
What does C stand for?
concentration of the drug in the bulk medium
What are some dosage forms that require a dissolution test?
tablets, capsules, ointments, creams, suppositories, pessaries, transdermal and implants
What is selection of testing conditions based on?
- Type of dosage form (tablets, suspensions, transdermal)
- Release pattern (immediate vs modified release)
- Physiology of the site of administration (GIT, skin, buccal, sublingual)
Dissolution apparatus 1
Rotating basket:
-disadvantage is that dosage may clog in mesh screen
Dissolution apparatus 2
Paddle:
- sinkers used for floating pills
- disadvantage is cone formation
Apparatus 1 & 2 are the most used for oral dosage forms:
Advantages ?
- widely accepted apparatus for dissolution test
- apparatus of first choice for solid oral dosage forms
- standardized
- easy to operate
- robust
- broad experience
Apparatus 1 & 2 are the most used for oral dosage forms:
Disadvantages ?
- limited volume
- simulation of GI transit not possible
- hydrodynamic conditions not known
Dissolution apparatus 3
Reciprocating cylinder:
- moves up and down, better simulates GI tract)
- originally used for extended release products
Dissolution apparatus 4
Flow Through Cell:
- adjust flow rate with a pump
- for solids, semi solids and liquids
- continuous flow rate or re-circlate media
Dissolution apparatus 4:
Advantages ?
- no limitation of media volume
- suitable for drugs with low solubility
- gentle hydrodynamic conditions
- simulation of the GI transit
- suitable for special dosage forms (powders, granules, implants)
Dissolution apparatus 4:
Disadvantages ?
- limited experience
- pump precision influences the results
What are apparatuses 5, 6, and 7 used for?
- specialized dosage forms (extended release and transdermals)
- Advantage: change medium pH and flow rate
Dissolution apparatus 5
Paddle over disk:
- Better for floaters
- Also good for transdermal patches, ointments, emulsions, bolus
Dissolution apparatus 6
Cylinder:
- good for patches that are too big for apparatus 5
- this one rotates
Dissolution apparatus 7
Reciprocating holder:
- similar to apparatus 6 but instead of rotating, it reciprocates (up and down)
- simulates GI tract more accurately
How is in vivo absorption assessed?
By calculating:
- AUC
- Cmax
- Tmax
IVIVC development:
Step 1 = ?
Dissolution
IVIV development:
Step 2 = ?
Permeability
What is the key to developing an IVIVC?
to identify a dissolution test that is descriptive of the in vivo absorption of the test compound
What is permeability?
The ability of the drug to penetrate across a membrane into the systemic circulation
What does the extent of permeation and ultimately absorption depend on?
- the physicochemical properties of the drug
- blood perfusion
What are the 4 levels of strength of the correlation?
Level A
Level B
Level C
Multiple Level C
Describe Level A correlation
- point to point relationship between intro dissolution rate and in vivo input rate of the drug from the dosage form
- utilize all of the “dissolution” and “plasma level” data available
- strongest level
Describe Level B correlation
- not a point to point relationship
- compares means
Describe Level C correlation
- a single time point correlation
- one dissolution time point is compared to one in vivo parameter
- does not reflect the entire shape of the plasma drug concentration curve
- this is the weakest level
Describe multiple level C correlation
- extension of level C correlation
- relates one or several in vivo parameters to in vitro drug release at several time points
- should be baed on at least 3 dissolution time points covering the early, middle, and late stage of the dissolution profile
BCS is a tool to classify drugs based on their ??
solubility and intestinal permeability
Class 1 BCS
high solubility
high permeability
Class 2 BCS
low solubility
high permeability
Class 3 BCS
high solubility
low permeability
Class 4 BCS
low solubility
low permeability
When combined with the dissolution of the drug product, the BCS takes into account 3 major factors that govern the rate and extent of drug absorption from solid oral dosage forms:
What are the 3 major factors?
- dissolution
- solubility
- intestinal permeability
When is IVIVC most likely predictable?
When the rate limiting step is drug release/dissolution
ex. highly permeable and poorly soluble (Class 2)
When is IVIVC limited?
1) When the rate limiting step is gastric emptying rate
2) When the rate limiting step in absorption is low permeability
