Investigation of Dry Powder Inhaler (DPI) Resistance and Aerosol Dispersion Timing on Emitted Aerosol Aerodynamic Particle Sizing by Multistage Cascade Impactor when Sampled Volume Is Reduced from Compendial Value of 4 L
- 379 Downloads
Compendial methods determining dry powder inhaler (DPI)-emitted aerosol aerodynamic particle size distribution (APSD) collect a 4-L air sample containing the aerosol bolus, where the flow, which propagates through the cascade impactor (CI) measurement system from the vacuum source, is used to actuate the inhaler. A previous article described outcomes with two CIs (Andersen eight-stage cascade impactor (ACI) and Next-Generation Pharmaceutical Impactor (NGI)) when the air sample volume was ≤4 L with moderate-resistance DPIs. This article extends that work, examining the hypothesis that DPI flow resistance may be a factor in determining outcomes. APSD measurements were made using the same CI systems with inhalers representing low and high flow resistance extremes (Cyclohaler® and HandiHaler® DPIs, respectively). The ratio of sample volume to internal dead space (normalized volume (V*)) was varied from 0.25 to 1.98 (NGI) and from 0.43 to 3.46 (ACI). Inhaler resistance was a contributing factor to the rate of bolus transfer; the higher resistance DPI completing bolus relocation to the NGI pre-separator via the inlet when V* was as small as 0.25, whereas only ca. 50% of the bolus mass was collected at this condition with the Cyclohaler® DPI. Size fractionation of the bolus from either DPI was completed within the ACI at smaller values of V* than within the NGI. Bolus transfer from the Cyclohaler® capsule and from the HandiHaler® to the ACI system were unaffected by the different flow rise time observed in the two different flow controller systems, and the effects the ACI-based on APSD measurements were marginal.
KEY WORDScascade impactor compendial method dry powder inhaler inhaler resistance sample volume
The authors wish to acknowledge the support of TEVA-Pharmachemie, Netherlands, and Boehringer-Ingelheim, Germany, for the supply of the DPI products and to other members of the Cascade Impactor Sub-Team of the EPAG for their advice and support during the experimental work and in the internal reviewing of this article.
- 1.European Directorate for the Quality of Medicines and Healthcare (EDQM): European Pharmacopeia 6(8). Chapter 2.9.18. Preparations for inhalations: aerodynamic assessment of fine particles. Strasbourg: Council of Europe; 2010.Google Scholar
- 2.US Pharmacopeial Convention. United States Pharmacopeia; USP 33-NF 28; Chapter 601—Physical tests and determinations: aerosols. United States Pharmacopeia, Rockville, MD, USA; 2010.Google Scholar
- 4.Mohammed H, Roberts DL, Copley M, Hammond M, Nichols SC, Mitchell JP. Effect of sampling volume on dry powder inhaler (DPI)-emitted aerosol aerodynamic particle size distributions (APSDs) measured by the Next-Generation Pharmaceutical Impactor (NGI) and the Andersen Eight-Stage Cascade Impactor (ACI). AAPS PharmSciTech. 2012;13(3):875–82.PubMedCrossRefPubMedCentralGoogle Scholar
- 5.Copley M. Improving inhaled product testing: methods for obtaining better in vitro-in vivo relationships. Pharm Tech (Europe). 2013;37(2):1–6. Available at: http://www.pharmtech.com/pharmtech/Peer-Reviewed+Research/Improving-Inhaled-Product-Testing-Methods-for-Obta/ArticleStandard/Article/detail/804866 visited June 20, 2013.Google Scholar
- 6.De Boer AH, Bolhuis GK, Gjaltema D, Hagedoorn P. Inhalation characteristics and their effects on in vitro drug delivery from dry powder inhalers: part 3: the effect of flow increase rate on the in vitro drug release from the Pulmicort 200 Turbuhaler. Int. J. Pharm. 1997; 153.Google Scholar
- 7.Beron KL, Grabek CE, Jung JA, Shelton CM. Flow rate ramp profile effects on the emitted dose from dry powder inhalers. In: Drug delivery to the lungs, 19. Edinburgh, The Aerosol Society; 2008, 61–4.Google Scholar
- 8.Van Oort M, Downey B. Cascade impaction of MDIs and DPIs: induction port, inlet cone, and pre-separator lid designs recommended for inclusion in the general test chapter “aerosols” <601> Pharm Forum. 1996;22(2):2204–10.Google Scholar
- 10.Olsson B, Asking L. Critical aspects of the function of inspiratory flow driven inhalers. J Aerosol Med. 1994;7S1:S43–7.Google Scholar
- 11.Donovan MJ, Kim SH, Raman V, Smyth HD. Dry powder inhaler device influence on carrier particle performance. J Pharm Sci. 2012;101(3):1097–107.Google Scholar
- 15.United States Pharmacopeial Convention. <601 > Inhalation and nasal drug products: aerosols, sprays, and powders—performance quality tests. Pharm Forum 2014;40(2): in press.Google Scholar
- 16.Roberts DL. Calibrating cascade impactors with particles—approaches and pitfalls. Inhalation. 2013;7(2):18–23.Google Scholar
- 17.United States Pharmacopeial Convention. In process revision: <601 > Inhalation and nasal drug products: aerosols, sprays, and powders—performance quality tests. Pharm. Forum. 2013;39(1) available on-line at: http://www.usppf.com/pf/pub/index.html visited July 9, 2013.
- 22.Olsson B, Borgström L, Lundbäck H, Svensson M. Validation of a general in vitro approach for prediction of total lung deposition in healthy adults. J. Aerosol Med. Pulmon. Deliv. 2013;26, in press.Google Scholar