Characterization of acoustic emission analysis in applications for inhalation device performance assessment

Graphical abstract Figure. No caption available. HighlightsA novel AE‐MVDA approach is developed to assess the performance of inhalation devices.AE‐MVDA can detect deviations from normal inhalation device performance.AE‐MVDA has a potential to add value as a cost‐effective non‐invasive technology. ABSTRACT Acoustic Emission (AE) measurement technology has gained wide appreciation in material sciences and process monitoring. In inhalation research, AE has been used for adherence indicating applications in clinical studies. Promising results from feasibility studies using AE combined with multivariate data analysis (AE‐MVDA) in the analysis of devices for inhalation have prompted a broader study reported in this paper. This work presents the novel application of AE‐MVDA for assessment of the combined inhalation device and formulation performance. The purpose is to evaluate the benefits that this technology can provide to inhalation product development programs. The work was carried out using two different dry powder inhaler device model systems while investigating different performance features. The devices were filled with dry powder formulations with both placebo and with active pharmaceutical ingredient (API). The acquired AE data was analyzed using multivariate data analysis tools such as Principal component analysis (PCA) and orthogonal projections to latent structures (OPLS). The AE profiles were indicative for device and formulation performance. Normal and deviating performances were readily picked up in the AE data. Moreover, performance trends between doses withdrawn from the inhalers were also observable. Lastly, differences in the AE profile between the formulations could be detected. The overall conclusion from the AE‐MVDA measurement approach evaluation is that it has the potential to add value as a cost‐effective, non‐invasive quality and performance monitoring technology both in development and in production of inhaled medicines.

[1]  Jonas Johansson,et al.  Matrix Effects in Quantitative Assessment of Pharmaceutical Tablets Using Transmission Raman and Near-Infrared (NIR) Spectroscopy , 2015, Applied spectroscopy.

[2]  O. Kvalheim,et al.  Multivariate data analysis in pharmaceutics: a tutorial review. , 2011, International journal of pharmaceutics.

[3]  C. R. Rios-Soberanis,et al.  Acoustic Emission Technique, an Overview as a Characterization Tool in Materials Science , 2011 .

[4]  Richard B Reilly,et al.  Monitoring Inhaler Inhalations Using an Acoustic Sensor Proximal to Inhaler Devices. , 2016, Journal of aerosol medicine and pulmonary drug delivery.

[5]  Richard B. Reilly,et al.  A Method to Assess Adherence in Inhaler Use through Analysis of Acoustic Recordings of Inhaler Events , 2014, PloS one.

[6]  Clive Davies,et al.  An experimental/computational approach for examining unconfined cohesive powder flow. , 2006, International journal of pharmaceutics.

[7]  Jolyon P. Mitchell,et al.  Aerodynamic particle size analysis of aerosols from pressurized metered-dose inhalers: Comparison of andersen 8-stage cascade impactor, next generation pharmaceutical impactor, and model 3321 aerodynamic particle sizer aerosol spectrometer , 2003, AAPS PharmSciTech.

[8]  Richard B. Reilly,et al.  The Acoustic Features of Inhalation can be Used to Quantify Aerosol Delivery from a Diskus™ Dry Powder Inhaler , 2014, Pharmaceutical Research.

[9]  Theodora Kourti,et al.  The Process Analytical Technology initiative and multivariate process analysis, monitoring and control , 2006, Analytical and bioanalytical chemistry.

[10]  R. Reilly,et al.  Acoustic Analysis of Inhaler Sounds From Community-Dwelling Asthmatic Patients for Automatic Assessment of Adherence , 2014, IEEE Journal of Translational Engineering in Health and Medicine.

[11]  Cristina Cristalli,et al.  Acoustic emissions for particle sizing of powders through signal processing techniques , 2011 .

[12]  C. Gendrin,et al.  Pharmaceutical applications of vibrational chemical imaging and chemometrics: a review. , 2008, Journal of pharmaceutical and biomedical analysis.

[13]  I. Larson,et al.  Insight into pressure drop dependent efficiencies of dry powder inhalers. , 2012, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[14]  Julie Varley,et al.  The uses of passive measurement of acoustic emissions from chemical engineering processes , 2001 .

[15]  Richard B. Reilly,et al.  An Acoustic-Based Method to Detect and Quantify the Effect of Exhalation into a Dry Powder Inhaler. , 2015, Journal of aerosol medicine and pulmonary drug delivery.

[16]  Hiroyuki Tsujimoto,et al.  Monitoring particle fluidization in a fluidized bed granulator with an acoustic emission sensor , 2000 .

[17]  D. R. Rudd,et al.  Application of acoustic emission to the monitoring and end point determination of a high shear granulation process. , 2000, International journal of pharmaceutics.

[18]  Edoardo Proverbio,et al.  Identification of corrosion mechanisms by univariate and multivariate statistical analysis during long term acoustic emission monitoring on a pre-stressed concrete beam , 2013 .