A mechanistic study of danazol dissolution in ionic surfactant solutions
β Scribed by Wei Sun; Cynthia K. Larive; Marylee Z. Southard
- Publisher
- John Wiley and Sons
- Year
- 2003
- Tongue
- English
- Weight
- 268 KB
- Volume
- 92
- Category
- Article
- ISSN
- 0022-3549
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β¦ Synopsis
This study examined the dissolution mechanism of the neutral drug danazol into solutions of the ionic surfactant sodium dodecyl sulfate (SDS). The effect of counterion concentration on drug dissolution was also studied by controlling the solution ionic strength (IS). The laminar flow apparatus of Shah and Nelson was chosen to measure in vitro dissolution rates for its simulation of physiological hydrodynamics. A mathematical model was developed to test the proposed mechanism for dissolution. Transport of the dissolved drug away from the tablet surface is the slow step in the process. Two major physicochemical properties, drug solubility in surfactant solutions and the effective diffusion coefficients used in the model, were measured in separate experiments for use in the transport model. Pulsed field proton nuclear magnetic resonance spectroscopy ((1)H NMR) was used to measure the drug diffusion coefficient. Actual drug dissolution rates were determined by multiplying the measured effluent drug concentration in the aqueous medium by its flow rate. The assumption of a transport-controlled dissolution rate was tested by plotting the measured dissolution rates as a function of medium flow rate in a log-log plot. A slope of 1/3 is predicted by the model and slopes of 0.26 to 0.32 were found experimentally, suggesting that the transport controlled mechanism is accurate. The model-predicted dissolution rates were compared with the experimental data. For SDS solutions without IS control, the model calculated data are 20-35% lower than the experimental results, whereas with IS control, the error is only 0.4-4%. We believe that there is significant electrostatic interaction between micelles in processes with low IS or poor IS control. In that situation, the nuclear magnetic resonance (NMR)-measured drug diffusivity would not be its actual value in the dissolution process.
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