BCS Class III Drugs: High Solubility - Low Permeability
The correct answer is D) High Solubility - Low Permeability. Class III drugs in the Biopharmaceutics Classification System are characterized by high aqueous solubility but low membrane permeability, making permeability the rate-limiting step for oral absorption 1, 2.
BCS Classification Framework
The Biopharmaceutics Classification System divides drugs into four categories based on two fundamental properties 1:
- Class I: High permeability, high solubility (HP:HS)
- Class II: High permeability, low solubility (HP:LS)
- Class III: Low permeability, high solubility (LP:HS)
- Class IV: Low permeability, low solubility (LP:LS)
Class III Drug Characteristics
Class III compounds are hydrophilic molecules with high aqueous solubility but poor absorption due to low permeability across biological membranes 3. While these drugs dissolve readily in gastrointestinal fluids, their inability to cross intestinal membranes becomes the rate-limiting step in achieving adequate bioavailability 2.
Specific Classification Criteria
The permeability boundary has been established at ≥80% human intestinal absorption for high permeability classification 1. For solubility classification, a cutoff of 200 μg/mL demonstrates 93% sensitivity and 86% specificity in predicting BCS solubility classes 4.
Clinical Implications
Poor membrane permeability results in significantly low bioavailability for Class III drugs despite their excellent solubility 2. This creates unique formulation challenges, as traditional approaches designed for poorly soluble drugs (Class II) are ineffective 3.
Common Pitfalls
Do not confuse Class III drugs with Class I drugs—both have high solubility, but Class III drugs have low permeability which fundamentally limits their absorption, whereas Class I drugs have high permeability and are well-absorbed 5.