Optimising the speed of rotation of the paddle
Experiments were carried out at paddle rotation speeds of 50, 75 and 100 rpm. With this dissolution apparatus 50 rpm is the
norm; however, the presence of the membrane holder necessitated an increase to 75 rpm because of the 'dead' volume between
the membrane holder and the base of the vessel, where stagnation could occur after volumes are withdrawn and replaced during
the sampling procedure.
The authors say…
Investigating the impact of drug loading
Varying the number of actuations during testing permits investigation of the impact of drug loading on dissolution behaviour.
For BD, increasing drug loading from 30 to 220 µg by increasing the number of actuations of the device during sample collection
has a marked influence on dissolution behaviour. On the other hand, AS dissolves rapidly even at high drug loadings (Figure 4).
Figure 4: The impact of drug loading on dissolution profile for (a) budesonide and (b) albuterol sulphate (Dissolution media:
simulated lung fluid (SLF); T= number
Increasing the thickness of the drug layer increases the amount of diffusion/dissolution activity required to release the
entire dose from beneath the membrane since the wetting and dissolution processes proceed inwards layer by layer. This has
a marked effect with the hydrophobic BD increasing the obstacles to dissolution, but with the hydrophilic AS this is not the
case. This suggests that powder wetting within the membrane holder may be an issue in certain circumstances, especially with
hydrophobic or poorly soluble formulations.
A simple solution to this problem is to use just a single actuation to obtain the thinnest possible layer of sample for analysis.
The practicality of this approach, however, depends on the limits of detection of the HPLC method for a given solvent/drug
formulation. In some cases, it will be necessary to use multiple actuations simply to obtain sufficient drug to enable detection
in the extracted samples. An alternative is to consider modification of the dissolution media within the constraint of reflecting
the composition of fluids present in the lung.