Bioavailability and bioequivalence are two core concepts of biopharmaceutics and regulatory science. They help determine how much of a drug reaches systemic circulation and whether two drug products behave the same in the body. These concepts are especially important when developing generic medicines and comparing different formulations of the same drug.
What Is Bioavailability?
Bioavailability (BA) refers to the fraction of an administered dose that reaches systemic circulation in its active form. It describes both the rate and extent of absorption.
Absolute Bioavailability
Compares the availability of a drug given orally to the same drug given intravenously.
Absolute BA = (AUCoral / AUCIV) × 100
Relative Bioavailability
Compares two different oral formulations of the same drug.
Relative BA = (AUCtest / AUCreference) × 100
Parameters Used to Measure Bioavailability
- Cmax – peak concentration
- Tmax – time to reach peak
- AUC – total drug exposure over time
Factors Affecting Bioavailability
- Drug solubility and dissolution rate
- Formulation and excipients
- Gastrointestinal pH and motility
- First-pass metabolism
- Food–drug interactions
- Patient-related factors (age, disease state)
What Is Bioequivalence?
Bioequivalence (BE) means that two drug products have similar bioavailability and produce comparable plasma drug concentration–time profiles.
Bioequivalence is required to approve generic drugs.
When Are Two Products Bioequivalent?
Two formulations are considered bioequivalent when their key pharmacokinetic parameters fall within acceptable limits:
- Cmax (peak concentration)
- AUC0–t (extent of absorption)
- AUC0–∞ (total exposure)
Regulatory Criteria
Most regulatory agencies (FDA, EMA) require the 90% confidence interval of the ratio (test/reference) of log-transformed PK values to fall within:
80% – 125%
Types of Bioequivalence Studies
1. Pharmacokinetic Studies
Most common and reliable. Compare AUC, Cmax, and Tmax.
2. Pharmacodynamic Studies
Used when plasma drug levels do not correlate directly with clinical effect.
3. Clinical Endpoint Studies
Used when PK measurements are not feasible (e.g., topical products).
4. In Vitro Dissolution Testing
Sometimes accepted as a surrogate for BE, especially in BCS Class I drugs.
Biopharmaceutics Classification System (BCS)
BCS helps predict the need for in vivo BE studies by classifying drugs based on solubility and permeability.
| Class | Solubility | Permeability |
|---|---|---|
| I | High | High |
| II | Low | High |
| III | High | Low |
| IV | Low | Low |
BCS-Based Biowaiver
Drugs in BCS Class I with rapid dissolution may receive a waiver for in vivo BE testing.
Importance of Bioavailability and Bioequivalence
1. Ensures Therapeutic Effectiveness
Good bioavailability ensures enough drug reaches systemic circulation to produce the desired effect.
2. Supports Development of Generic Medicines
Bioequivalence guarantees that generics work the same as brand-name products.
3. Prevents Therapeutic Failure
Poor bioavailability may lead to subtherapeutic levels.
4. Ensures Patient Safety
Bioequivalence prevents unexpected toxicity or clinical failure.
Applications in Pharmaceutical Industry
- Formulation development
- Switching between brands
- Generic product approval
- Clinical trial design
Detailed Notes:
For PDF style full-color notes, open the complete study material below:
PATH: PHARMD/ PHARMD NOTES/ PHARMD FOURTH YEAR NOTES/ BIOPHARMACEUTICS AND PHARMACOKINETICS/ BIOAVAILABILITY AND BIOEQUIVALENCE.
