1. When is a Fasting Study Required?
A fasting study is typically the default requirement for most oral formulations, especially immediate-release products. This condition is chosen when the RLD label does not recommend taking the drug with food or specifically states that it should be taken on an empty stomach. Fasting studies eliminate the variability introduced by food, thus allowing a clearer comparison of the pharmacokinetics of the test and reference formulations.
2. When is a Fed Study Required?
Fed studies are required when the RLD labeling recommends that the product be taken with food or when food significantly impacts the drug’s absorption. This is particularly important for drugs with low solubility (e.g., BCS Class II or IV) and for modified-release formulations where gastrointestinal conditions, including the presence of food, can alter drug release and absorption. Regulatory agencies like the USFDA and EMA often require fed BE studies to assess whether the test product can maintain performance consistency in a fed state.
3. Selection of Dissolution Media Based on Dosing Conditions
The choice of dissolution media must reflect the physiological environment corresponding to the BE study condition.
Fasting State Dissolution Media
When a fasting study is conducted, the dissolution media should mimic the gastrointestinal environment of a fasted individual. Commonly used media include:
- 0.1 N Hydrochloric Acid (to simulate gastric fluid)
- Simulated Gastric Fluid (SGF)
- Fasted State Simulated Intestinal Fluid (FaSSIF)
These media help predict how the drug will dissolve and behave in the absence of food.
Fed State Dissolution Media
In the case of fed studies, dissolution testing should be conducted in media that replicate the gastrointestinal conditions after a meal. Appropriate media include:
4. Dissolution Media and BE Study Alignment
It is important to align the dissolution media with the dosing condition of the BE study. If regulatory agencies require both fasting and fed BE studies for a drug product, the formulation must demonstrate similar in vitro performance in both FaSSIF and FeSSIF. Matching the dissolution profiles in these biorelevant media strengthens confidence in achieving in vivo bioequivalence. The f₂ similarity factor is commonly used to compare profiles and supports formulation bridging.
5. Practical Example
Consider a weakly basic BCS Class II drug with low solubility in acidic media but improved solubility in the presence of bile salts. If the RLD label recommends taking the drug with food, a fed BE study becomes mandatory. In such a case, in vitro dissolution testing in FeSSIF is essential to simulate the in vivo fed-state environment. If the test product exhibits a dissolution profile similar to the RLD in FeSSIF, it provides supportive evidence of comparable bioavailability under fed conditions.
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