Bioavailability & Bioequivalence priniciples

1. Objectives
– describe bioequivalence and its importance
– Practice estimation of bioavailability of different
dosage forms

2. BA/BE
Definitions
• Bioavailability is defined as the rate and
extent to which the active drug ingredient is
absorbed and becomes available at the site
of drug action
Two drug products are said to be
bioequivalent if their rates and extents of
absorption do not show a significant
difference.

3. BA/BE
Definitions
Pharmaceutical equivalence
Medicinal products are pharmaceutical equivalents if they contain the
same amount of the same active substance in the same dosage form that
meet comparable standards.
Not necessarily bioequivalent because of different excipients and
manufacturing methods
Bioequivalence
Two medicinal products are bioequivalent if their bioavailabilities after
administration in the same molar dose are similar to such a degree that
their effects with respect to both efficacy and safety will be essentially the
same.
Bioequivalence study
A comparative bioavailability study designed to establish equivalence
between two products, a ‘test’ product compared to a ‘reference’ product

4. BA/BE
Ground reality
• Bioavailability
– Assessed as “Rate” & “Extent” of Absorption
– Peak (Cmax) & Total (AUC) Exposure
• Bioequivalence
– Equivalent “Rate” & “Extent” of Absorption
– Equivalent Peak (Cmax) & Total (AUC)
Exposure

5. BA/BE
Fundamental Bioequivalence
Assumption
When a generic drug is claimed
bioequivalent to a brand-name drug, it
is assumed that they are
therapeutically equivalent.

6. • The phase of the curve over which absorption takes place
is known as the absorption phase, and the time that the
maximum concentration occurs is called T max.
• Area under the serum concentration/time curve (AUC), the maximum
concentration (C max ), time that the maximum concentration occurs (Tmax)
are considered primary bioavailability parameters.
• When the AUC, C max , and T max are the same within statistical limits for two
dosage forms of the same drug, the dosage forms are considered to be
bioequivalent.

7. 9/11/2022 7
Prof. Mazen Qato

8. 8
1) AUC - extent of absorption
2) Cmax - rate (but also extent) of
absorption
3) tmax - rate of absorption
The Three Major PK Parameters
to
Assess Bioequivalence are:

9. 9
ER vs IR Formulation
Similar AUC, lower Cmax and longer tmax: Flatter is Better

10. 10
ER vs IR VPA:Similar Exposure &Fluctuati

11. SDL
• Design of BE studies
• Drugs with long half life , impact of food,
critical dose , statistical issues