Limitations in Dissolution Testing

1. Poor In-Vivo Correlation (IVIVC)

   • Dissolution data may not accurately predict drug release in the human body due to complex gastrointestinal (GI) conditions.

2. Single-Media Testing

   • Conventional USP tests often use only one dissolution medium, not reflecting varying pH and enzymes in the GI tract.

3. Static Conditions

   • USP apparatus operates at constant agitation and temperature, which doesn’t mimic real GI motility changes.

4. Limited for Novel Dosage Forms

   • Poorly suited for advanced drug delivery systems like nanoparticles, liposomes, and depot injections.

5. Lack of Biorelevance

   • Standard media (e.g., pH 6.8 phosphate buffer) may not replicate fed/fasted conditions or bile salt content.

6. End-Point Testing

   • Focuses on a final result rather than continuous real-time drug release monitoring.

7. Inter-Laboratory Variability

   • Differences in equipment calibration, media preparation, and operator handling can affect reproducibility.

Advances in Dissolution Testing

1. Biorelevant Media

   • Use of simulated gastric fluid (SGF), simulated intestinal fluid (SIF), FaSSIF (fasted state), FeSSIF (fed state) to better mimic in-vivo conditions.

2. In-Vitro–In-Vivo Correlation (IVIVC) Models

   • Statistical and computational models linking dissolution results with pharmacokinetic data.

3. Automation & High-Throughput Systems

   • Robotic sampling, media replacement, and automated data capture for better precision and reduced human error.

4. Real-Time Dissolution Monitoring

   • Use of fiber-optic UV probes or in-situ Raman spectroscopy for continuous drug release measurement.

5. Advanced Apparatus Designs

   • USP Apparatus 4 (Flow-Through Cell) and miniaturized versions for poorly soluble drugs and special dosage forms.

6. Dissolution Under Physiological Conditions

   • Dynamic pH-change testing to simulate stomach-to-intestine transition.

7. Integration with Computational Modelling

   • Use of PBPK (Physiologically Based Pharmacokinetic) models to predict in-vivo performance more accurately.

✅ Conclusion:
While conventional dissolution testing is a critical QC and regulatory requirement, it has limitations in predicting real in-vivo performance. Advances in biorelevant media, automation, and in-situ monitoring are making dissolution testing more predictive, efficient, and relevant for modern drug delivery systems.