Dissolution of inhalation powders
Dissolution of inhalation formulations is interesting to study, both from a quality control perspective and as a possibility to correlate in-vitro data with in-vivo performance. Difference in dissolution rate between eg substances, particle sizes and formulations can be revealed.
Literature studies on the subject provides knowledge on the different techniques that have been used for dissolution testing and their respective strengths and shortcomings. It is apparent that the diffusion principle, where the active drug substance is dissolved in a thin liquid layer on a porous membrane, offers many advantages and so this approach was used. Samples were generated by placing a filter with 1 µm pore size at appropriate stages in the Next Generation Impactor (NGI) and collecting a desired number of doses of a selected particle size range.
The dissolution experiment itself was performed by letting the filter float on the surface of the dissolution medium, e.g., phosphate buffered saline (pH 7.4), in a Petri dish using a magnetic bar as stirrer. The drug side was turned upwards, i.e. in contact with air. Samples were collected at specified intervals and the content of active determined by HPLC.
Large differences in dissolution rates between different compounds were seen, correlating with the substance solubility in the medium. When comparing substance particle size, a difference was recorded with a faster rate seen for the smaller size ranges. Two marketed products were also studied, one originator and one generic copy with the same substance and labelled amount per dose. It was apparent that the dissolution rate of the active substance differed between the two products.