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A STELLA simulation model for in vitro dissolution testing of respirable size particles
Basanth Babu Eedara1, Ian G Tucker2, Shyamal C Das3
1School of Pharmacy, University of Otago, 18 Frederick St, Dunedin, 9054, New Zealand.
Scientific Reports
|December 8, 2019
Summary
A novel in vitro dissolution testing model accurately predicts drug release from respirable particles. The simulation distinguished dissolution rates for moxifloxacin and ethionamide, highlighting formulation differences.
Area of Science:
- Pharmaceutical Sciences
- Drug Delivery Systems
- Computational Modeling
Background:
- In vitro dissolution testing is crucial for quality control and predicting in vivo drug release.
- A custom apparatus was developed for dissolution testing of dry powder formulations in small, stationary media volumes.
- Understanding dissolution parameters for respirable particles is essential for effective drug delivery.
Purpose of the Study:
- To develop and validate a simulation model for predicting drug permeation from respirable particles.
- To differentiate the dissolution behavior of two anti-tubercular drugs with varying solubilities: moxifloxacin and ethionamide.
- To identify key parameters influencing drug dissolution and diffusion from respirable particles.
Main Methods:
- A STELLA-based simulation model was constructed to predict drug permeation.
- Simulations were performed for moxifloxacin and ethionamide, comparing dissolution from solution versus respirable particles.
- Sensitivity analysis was conducted to assess the impact of mucus volume and membrane thickness on permeation.
Main Results:
- Simulated permeation profiles for moxifloxacin were similar from solution and particles, indicating rapid dissolution.
- Ethionamide showed slower permeation from particles compared to solution, suggesting slow dissolution.
- Sensitivity analysis revealed that increased mucus volume and membrane thickness reduce drug permeation.
Conclusions:
- The simulation model successfully predicted and distinguished the dissolution behavior of moxifloxacin and ethionamide from respirable particles.
- The model serves as a valuable tool for quality control and formulation development.
- Further refinement of the model with experimental data is recommended for enhanced accuracy.
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