IVIVC Flashcards by Sam Myers

Innovator = ?

Brand (ex. Advil)

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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

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In vitro = ?

within the glass

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In vivo = ?

within the living

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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

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In vitro property is ?

the rate of drug dissolution or release

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In vivo response is ?

the plasma drug concentration or amount of drug absorbed (bioavailability)

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Why was IVIVC developed?

To minimize the need for additional bioavailability studies as part of the formulation design

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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)

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Noyes-Whitney Equation:

What does D stand for?

diffusion coefficient (diffusivity) of the drug

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Noyes-Whitney Equation:

What does the S stand for?

surface area of the drug

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Noyes-Whitney Equation:

What does the h stand for?

thickness of the diffusion layer liquid film

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Noyes-Whitney Equation:

What does the Cs stand for?

saturation solubility of the drug

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Noyes-Whitney Equation:

What does C stand for?

concentration of the drug in the bulk medium

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What are some dosage forms that require a dissolution test?

tablets, capsules, ointments, creams, suppositories, pessaries, transdermal and implants

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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)

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Dissolution apparatus 1

Rotating basket:

-disadvantage is that dosage may clog in mesh screen

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Dissolution apparatus 2

Paddle:

sinkers used for floating pills
disadvantage is cone formation

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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