Bioavailability and Bioequivalence
Bioavailability and Bioequivalence
𝐵𝑖𝑜𝑎𝑣𝑎𝑖𝑙𝑎𝑏𝑙𝑒 𝑑𝑜𝑠𝑒
F=
𝐴𝑑𝑚𝑖𝑛𝑖𝑠𝑡𝑒𝑟𝑒𝑑 𝑑𝑜𝑠𝑒
Types of bioavailability
There are two types bioavailability
1. Absolute Bioavailability
2. Relative Bioavailability
1. Absolute Bioavailability
i. Compares the bioavailability of the active drug in systemic circulation following non-
intravenous administration with the same drug following intravenous administration
ii. For drugs administered intravenously, bioavailability is 100%
iii. Determination of the best administration route
Definition
FDA: A predictive mathematical model describing the relationship between an in vitro
property of dosage form (usually the rate or extent of drug dissolution or release) and a
relevant in vivo response, e.g., plasma drug concentration or amount of drug
❖ The concept of IVIVC has been extensively discussed for modified release dosage forms.
❖ This is because the dissolution behavior of of the drug from ER or MR product is the rate
limiting factor for absorption in GIT
❖ This is why IVIVC are expected more generally for ER formulations than with IR products
especially when the latter releases the drug rapidly (>80 % in < 20 minutes) But, it does
not mean that IVIVC cannot be applied for IR products
❖ In recent times, IVIVC for parenterals, transdermals, pulmonary formulations etc. are
also coming
Bioequivalence studies
Bioequivalence (BE): the absence of a significant difference in the rate and extent to which
the active ingredient or active moiety in pharmaceutical equivalents or pharmaceutical
alternatives becomes available at the site of drug action when administered at the same
molar dose under similar conditions in an appropriately designed study
Two products are bioequivalent if
• They are pharmaceutically equivalent
• Bioavailability's (both rate and extent) after administration in the same molar dose are
similar to such a degree that their effects can be expected to be essentially the same
Pharmaceutical Equivalents
• Contain the same amount of the same active substance in the same dosage form meet
the same or comparable standards intended to be administered by the same route
• Pharmaceutical equivalence by itself does not necessarily imply therapeutic equivalence
Bioequivalence studies
Bioequivalence studies
Therapeutic equivalence
Two products are therapeutically equivalent if
• Pharmaceutically equivalent
• Their effects, with respect to both efficacy and safety, will be essentially
the same as derived from appropriate studies
i. Bioequivalence studies
ii. Pharmacodynamic studies
iii. Clinical studies
iv. In vitro studies
Bioequivalence studies
Need of bioequivalence studies
❖No clinical studies have been performed in patients with the Generic Product to support
its Efficacy and Safety
❖With data to support similar in vivo performance (= Bioequivalence) Efficacy and Safety
data can be extrapolated from the Innovator Product to the Generic Product.
Ultimate: Bioequivalence studies impact of changes to the dosage form process after pivotal
studies commence to ensure product on the market is comparable to that upon which the
efficacy is based
Bioequivalence studies
Goals of BE
Ultimate: Bioequivalence studies impact of changes to the dosage form process after pivotal
studies commence to ensure product on the market is comparable to that upon which the
efficacy is based
• Establish that a new formulation has therapeutic equivalence in the rate and extent of
absorption to the reference drug product
• Important for linking the commercial drug product to clinical trial material at time of NDA
• Important for post-approval changes in the marketed drug formulation
NDA vs. ANDA Review Process
Dissolution Rate “Dissolution rate may be defined as the amount of drug substance that goes in to
solution per unit time under standardized conditions of liquid-solid interface, temperature & solvent
composition.” Dissolution rate is given by Noyes-Whitney equation-
Under non sink condition dc/dt = KS (Cs-C) dc/dt =DS/h (Cs-C)
Where ,
dc/dt = rate of drug dissolution, K= dissolution rate constant, S=surface area of the particle, (Cs-
C)=concentration gradient, D= diffusion coefficient of drug in solution, h= thickness of diffusion layer.
Process of dissolution : The process of dissolution involves breaking of inter-ionic or intermolecular bonds in
the solute, the separation of the molecules of the solvent to provide space in the solvent for the solute, and
the interaction between the solvent and solute molecule or ion.
Methods to enhance the dissolution rates