A mechanistic study of danazol dissolution in ionic surfactant solutions

Area of Science:

• Physical Chemistry
• Pharmaceutical Sciences
• Materials Science

Background:

• Understanding drug dissolution mechanisms is crucial for optimizing oral drug delivery.
• Ionic surfactants like sodium dodecyl sulfate (SDS) are commonly used in pharmaceutical formulations.
• The influence of solution properties, such as ionic strength (IS), on drug dissolution requires detailed investigation.

Purpose of the Study:

• To elucidate the dissolution mechanism of the neutral drug danazol in SDS solutions.
• To investigate the impact of counterion concentration, controlled by IS, on danazol dissolution rates.
• To develop and validate a mathematical model for predicting drug dissolution.

Main Methods:

• Utilized the Shah and Nelson laminar flow apparatus for in vitro dissolution rate measurements.
• Employed pulsed field proton nuclear magnetic resonance spectroscopy (¹H NMR) to determine drug diffusion coefficients.
• Developed a transport model incorporating drug solubility and diffusion coefficients, validated against experimental data.

Main Results:

• Dissolution rates were found to be transport-controlled, with experimental log-log plot slopes (0.26-0.32) closely matching the model's prediction (1/3).
• A mathematical model accurately predicted dissolution rates when ionic strength was controlled (0.4-4% error).
• Uncontrolled ionic strength led to significant deviations (20-35% error), attributed to electrostatic interactions between micelles.

Conclusions:

• The dissolution of danazol in SDS solutions is primarily governed by the transport of dissolved drug away from the surface.
• Accurate modeling and prediction of dissolution require careful control of solution ionic strength to minimize micellar electrostatic interactions.
• The study highlights the importance of physicochemical properties and solution conditions in drug dissolution processes.