IVIV

Question 1

In Vitro Def

Answer 1

In lab, outside of a living organism. Critical factor: dissolution. % of drug absorbed

Question 2

In Vivo Def

Answer 2

Inside living organism (animal or human). Critical factor: absorption. % drug absorbed & serum drug conc

Question 3

IVIV Outline

Answer 3

Relationship between in vitro dissolution/release versus in vivo absorption. Drug dissolved in buffer (w/ conditions pH, temp, ect) identical to human body alternative to human in vivo

Question 4

In Vitro In Vivo Correlation (IVIVC)

Answer 4

Predictive mathematical model describing relationship between in vitro dosage form properties and in vivo response. Informed by structure analysis

Question 5

Correlation Outline

Answer 5

Establishing relationship/connection between 2 or more things

Question 6

IVIVC Technology

Answer 6

Regulatory (biowaiver app), Drug dev (product performance) and Manufacturing (Formulation optimisation)

Question 7

Biowaiver Outline

Answer 7

Proving generic drug works same as original to skip clinical studies. Granted when: high solubility & absorption (Class 1), similar formulation and follows reg guidelines

Question 8

Bioequivalence Requirements

Answer 8

Pharmaceutical equivalence and Bioequivalence study OR IVIC biowaver

Question 9

Pharmaceutical Equivalence Outline

Answer 9

Ensures that they’re structurally similar

Question 10

Bioequivilance Outline

Answer 10

Check dissolution and absorption correlation

Question 11

IVIVC Potential Application

Answer 11

Optimise formulation, Permit biowaivers and Therapeutic justifications

Question 12

IVIVC Level A

Answer 12

Highest category of correlation, point-to-point IVIV absorption rate. Most preferred allows biowavers defines direct relationship and measures

Question 13

IVIVC Convolution Outline

Answer 13

Mathematical operations used to predict in vivo plasma concentration-time profiles (measuring absorption)

Question 14

IVIVC Deconvolution Outline

Answer 14

In vivo drug absorption profile from plasma concentration-time data

Question 15

IVIVC Level B

Answer 15

Mean in vitro dissolution profile vs Mean in vitro absorption profile: mean to mean comparison. Indirect mathematical relationship

Question 16

IVIVC Level C

Answer 16

Correlation is visible from when 50% dissolved/absorbed. Few points are correlated but not all. Record section of times that points correlate

Question 17

IVIVC Level D

Answer 17

No correlation, will never qualify for biowaver

Question 18

Pharmaceutical Availability Def

Answer 18

Release active substance facilitated by disintegration and dissolution

Question 19

Biological Availability Def

Answer 19

Elimination by 1st pass metabolism and appearance systemic circulation. Up to permeability absorption and then after bioavailability

Question 20

How To Identify Class 1

Answer 20

Dissolution rate is limiting step

Question 21

Dose Number (D0)

Answer 21

Predict whether compound will be reasonably absorbed based on solubility. D0 > 1 = poorly soluble (dissolution limited). D0 < 1 = soluble (dissolves in 250ml)

Question 22

Dose Number Calc

Answer 22

D0 = D/(V x Cs) ((Cs = solubility in water))

Question 23

Dissolution Number (Dn)

Answer 23

Represents relative rate of drug dissolution in comparison to GI transit time

Question 24

Dissolution Number Calc

Answer 24

Mean residence time / mean dissolution time

Question 25

Absorption Number (An) Outline

Answer 25

Ratio of mean residence time in GIT mean absorption time

Question 26

Factors Impacting Predictions

Answer 26

Widely recognised correlations exist between in vitro dissolution and in vivo absorption limited progress. Physicochemical, biopharmaceutical and physiological

Question 27

Physicochemical Outline

Answer 27

Predicts in vivo absorption, prerequisite drug absorption and clinical efficacy. Characteristics: Solubility, Particle size and Diffusivity

Question 28

Maximum Absorbable Dose

Answer 28

(Solubility x Ka) X (Small Intestinal Water Volume (250ml)) X (residence time in SI (3hs))

Question 29

Transcellular Permeability Calculations

Answer 29

(membrane water partition X membrane diffusivity) / (membrane thickness)

Question 30

Absorption Potential (AP)

Answer 30

log( (partition coefficient x fraction unionised 6.5)/ dose number)