IVIVC & Bioequivalence Flashcards
What is IVIVC?
in vitro in vivo correlation
a predictive mathematical model describing the relationship between an in vitro property of a dosage form and an in vivo response
What is bioequivalence?
different brands of the same active pharmaceutical ingredient in the same formulation should act the same in the body
- efficacy and toxicity
absence of significant difference in the rate and extent to which API becomes available at the site of action
typically not needed for generic medicine as they are qualitatively and quantitatively the same
- similar dissolution and disintegration parameters in vivo
is needed for MR products
What is a typical bioequivalence trial?
randomised double blind two way crossover
absolute minimum of twelve subjects
- BMI 18.5-30
- either gender
requires a washout period of at least 5x the half life
often a residential stay is needed
- food controlled, blood samples need to be taken
What is the acceptable interval recommended by the EMA? How is it different for narrow therapeutic index drugs?
90% confidence interval is between 80-125% of the reference product via ANOVA (analysis of variance)
for products with narrow therapeutic index the acceptable index for AUC is narrowed to 90-111.11%
- drugs like warfarin, theophylline, lithium, phenytoin
What are the types of in vivo and in vitro properties?
in vivo
- plasma drug concentration
in vitro
- dissolution
What are the main uses for IVIVC? How are they beneficial?
main uses
- reformulations
- alterations in excipients/dosage form
- product development
benefits
- lower costs
= fewer costly trials and small amount of API required
- increased rate of development
What are the three types of correlation in IVIVC trials?
level A
- strongest correlation
- point to point relationship between in vivo input rate (absorption) and in vitro dissolution
level B
- utilises the principles of statistical moment analysis
- compares mean in vitro dissolution time with either mean residence time or mean in vivo dissolution time
level C
- relates one dissolution time point to a single pharmacokinetic parameter
- only useful as a guide in formulation development
What are the types of dissolution tests?
types I and II - most commonly used
type III - reciprocating cylinder
- appropriate for modified release formulations = but only allows low volumes to be used
type IV - flow through cell
- uses unlimited media = is good for poorly soluble drugs
What is a TNO gastrointestinal model?
chambers mimic the
- stomach, small intestine and large intestine
simulates the fed or fasted state and drug absorption via dialysis
When is dissolution IVIVC done?
is typical for modified release dosage forms
- where dissolution/release is the rate limiting step
What solvent can be used in dissolution IVIVC? What is least likely to be used?
solvent used
- bicarbonate
- phosphate
- milk
- sodium plate
solvent unlikely to be used
- ethanol
