Improving Inhaled Product Testing: Methods for Obtaining Better In vitro-In vivo Relationships - Pharmaceutical Technology

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Improving Inhaled Product Testing: Methods for Obtaining Better In vitro-In vivo Relationships
Even in an industry in which all product development is complicated by the intricacies of human biology, orally inhaled products (OIP) stand out as singularly demanding.

Pharmaceutical Technology
Volume 37, Issue 2

Improving productivity using AIM

In recent years, the search for improved productivity in inhaler product testing has fueled interest in AIM (20). A key focus is quality control (QC) testing, but the approach also holds promise for R&D. AIM involves separation of a sample into far fewer fractions than a multistage cascade impactor, thereby delivering some important benefits:

  • Faster analytical throughput
  • Less complicated analysis, which results in reduced likelihood of error
  • Ease of automation.

Figure 5: Schematic illustrating the Abbreviated Impactor Measurement–human respiratory tract concept, which involves the use of two impaction stages (CPM is coarse particle mass, FPM is fine particle mass, EPM is extra-fine particle mass, IP is inhaled product).
In R&D, the proposal is that requirements for better productivity may be met by applying the human respiratory tract (HRT) version of the AIM concept, which focuses attention on those parts of the APSD that are crucial for the assessment of drug-delivery performance (see Figure 5). Published studies highlight industrial interest in this approach (21–23). The potential that AIM offers for reducing human error and enhancing data integrity may also support the development of better IVIVRs that are based on more secure results.

AIM-HRT consists of two impaction stages, a filter, and a spacer to modify aerodynamic performance. It separates the dose into a coarse particle mass (>5 microns), a fine particle mass (<5 microns), and an extra-fine particle mass (<1 micron). These fractions would typically be associated with mouth/throat deposition, lung deposition, and, potentially, loss via exhalation, respectively. The technology, however, enables the cut-off diameter of the stages to be varied, as necessary, to produce results that more closely correlate with measured in vivo data, if available. Some studies indicate that this can be achieved by using a cut-off diameter closer to 3 microns rather than 5 microns (24). In the future, AIM may, therefore, enable the acceleration of design of experiments and screening trials although there is considerable debate about its uptake.

Looking ahead

The conventional test cascade-impactor setup used to measure the APSD of all OIPs was originally developed with QC testing in mind. It fulfills this function well because it allows a highly discriminating and reproducible measure of product quality. The conventional setup has drawbacks, however, for researchers trying to access a more detailed understanding of inhalation technology and obtain better IVIVRs that will further development. One concern is better representation of deposition behavior in the mouth and throat, and another is the application of more representative breathing profiles during testing, in which they may have an impact on dose emission and the resulting aerosol APSD generated. The issue of analytical productivity remains pressing in an environment of ever deeper cost-cutting.

Instrument suppliers are responding positively to these requirements by introducing new products such as the mixing inlet, sophisticated breathing simulators, new interfaces such as the AIT, and AIM equipment that streamlines testing. These new products potentially allow for significant advances in the area of inhaled-product testing within the R&D environment. In the future, such innovations offer the opportunity to shape in vitro testing into a far more effective tool for the rapid advancement of inhaler technology for the widest possible range of drug therapies.


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