Abstract
In vitro dissolution testing is a useful quality control tool to discriminate the formulations and to approximate the in vivo drug release profiles. A dissolution apparatus has been custom-made for dissolution testing of dry powder formulations in a small volume of stationary medium (25 μL spread over 4.91 cm2 area i.e. ~50 μm thick). To understand the system and predict the key parameters which influence the dissolution of respirable size particles, a simulation model was constructed using STELLA modeling software. Using this model, the permeation (dissolution followed by diffusion through the membrane) of two anti-tubercular drugs of differing solubilities, moxifloxacin (17.68 ± 0.85 mg mL−1) and ethionamide (0.46 ± 0.02 mg mL−1), from the respirable size particles and their diffusion from a solution were simulated. The simulated permeation profiles of moxifloxacin from solution and respirable size particles were similar, indicating fast dissolution of the particles. However, the simulated permeation profile of ethionamide from respirable size particles showed slower permeation compared to the solution indicating the slow dissolution of the respirable size particles of ethionamide. The sensitivity analysis suggested that increased mucus volume and membrane thickness decreased the permeation of drug. While this model was useful in predicting and distinguishing the dissolution behaviours of respirable size moxifloxacin and ethionamide, further improvement could be made using appropriate initial parameter values obtained by experiments.
Highlights
In vitro dissolution testing is a useful quality control tool to discriminate the formulations and to approximate the in vivo drug release profiles
The STELLA simulation model described here was used to simulate the permeation of a drug from respirable size particles of two anti-tubercular drugs, moxifloxacin and ethionamide, that have different aqueous solubilities
The simulations for the permeation of moxifloxacin and ethionamide from solutions were conducted using the initial parameter values shown in Supplementary Table S1
Summary
In vitro dissolution testing is a useful quality control tool to discriminate the formulations and to approximate the in vivo drug release profiles. To understand the system and predict the key parameters which influence the dissolution of respirable size particles, a simulation model was constructed using STELLA modeling software Using this model, the permeation (dissolution followed by diffusion through the membrane) of two anti-tubercular drugs of differing solubilities, moxifloxacin (17.68 ± 0.85 mg mL−1) and ethionamide (0.46 ± 0.02 mg mL−1), from the respirable size particles and their diffusion from a solution were simulated. The sensitivity analysis suggested that increased mucus volume and membrane thickness decreased the permeation of drug While this model was useful in predicting and distinguishing the dissolution behaviours of respirable size moxifloxacin and ethionamide, further improvement could be made using appropriate initial parameter values obtained by experiments. They have used pharmacokinetic results from laboratory animal (rat) studies together with drug permeability, mucociliary clearance and pulmonary metabolism data to predict the pharmacokinetics of inhaled drugs in humans[22]
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