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

Experimental study: Assessing AIT performance

The APSD of a pMDI (active ingredient salbutamol) was measured in a collaborative project with Melbourn Scientific (UK) using an impactor (Next Generation Impactor, Copley Scientific) with both the USP induction port and an AIT (7). Testing was carried out at a flow rate of 30 L/min, according to pharmacopeial guidance for MDIs, with six replicate measurements conducted in each case. All collection stages of the NGI and the AIT were coated with silicone oil applied in n-hexane solution (1% w/v), which is a standard practice that reduces particle bounce (i.e., the re-entrainment of particles impacting at high velocities). The USP induction port was left uncoated as is done for routine testing.


Table I: Summary collection data for a pressurized metered-dose inhaler (pMDI) tested using a United States Pharmacopeia (USP) induction port and Alberta Idealized Throat (SD is standard deviation, T/MP is throat/mouthpiece, g a/ac is g active/actuation, MOC is micro orifice collector, FPD is fine particle dose, FPF is fine particle fraction, GSD is geometric standard deviation, MMAD is mass median aerodynamic diameter).
Table I shows averaged collection data for each component of the test equipment including a combined mass recorded for the throat and inhaler mouthpiece. Values for fine-particle dose (FPD), fine-particle fraction (FPF), geometric standard-deviation (GSD), and mass median aerodynamic diameter (MMAD) were determined from these data. Calculations were based on total emitted mass/actuation and the assumption of a 5-micron upper limit for FPD and FPF.

Deposition data for the throat/mouthpiece shows that the AIT captures more of the dose, thus reducing the mass of drug entering the cascade impactor. This result is attributed to differences in the geometry of the two interfaces, rather than any coating effect (7).


Figure 2: For this pressurized metered-dose inhaler, use of the Alberta Idealized Throat shifts the measured, cumulative, aerodynamic particle size distribution to finer size distributions relative to the standard United States Pharmacopeia (USP) induction port.
Figure 2 shows averaged cumulative APSDs based on the amount of material exiting the mouthpiece/throat. Here, use of the AIT shifts the APSD to finer sizes across the entire size range, thus suggesting that not all particle sizes are equally retained relative to the standard induction port. In a parallel experiment with a DPI, the same effect was observed (7). These are early results and further research is required. The results, however, underline the fact that better representation of mouth/throat deposition may influence assessments of regional deposition in the lung, which is a function of particle size, as well as estimates of whole lung deposition. From an in vitro perspective, use of the AIT ensures that only the portion of the aerosol that would actually deposit in the lung is sized by the cascade impactor, therefore providing more relevant data.


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