Dissolution Testing For Inhaled drugs - Pharmaceutical Technology

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Dissolution Testing For Inhaled drugs
Although there are no regulatory requirements or established pharmacopoeial techniques for the dissolution testing of inhaled drugs, such testing can potentially open up the opportunity to tailor formulation properties. The authors explain how a new technique using standard dissolution test equipment in combination with US Pharmacopeia methods for the dissolution testing of solid dosage forms can be used to differentiate the solubility of orally inhaled products.

Pharmaceutical Technology Europe
Volume 22, Issue 11

Optimising the speed of rotation of the paddle

The authors say…
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'dead' volume between the membrane holder and the base of the vessel, where stagnation could occur after volumes are withdrawn and replaced during the sampling procedure.

Investigating the impact of drug loading

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
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 g 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).

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.


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