PRACTICES OF COATING COLLECTION SURFACES OF CASCADE IMPACTORS: A SURVEY OF MEMBERS OF THE EUROPEAN PHARMACEUTICAL AEROSOL GROUP (EPAG)

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1 PRACTICES OF COATING COLLECTION SURFACES OF CASCADE IMPACTORS: A SURVEY OF MEMBERS OF THE EUROPEAN PHARMACEUTICAL AEROSOL GROUP () J.P. Mitchell on behalf of members of the European Pharmaceutical Aerosol Group Summary members evaluate many different aerosols from both pressurized metered dose inhalers (pmdis) and dry powder inhalers (s) by the use of a cascade impactor. It is widely recognized that pre-coating of particle collection surfaces is a prerequisite in testing to avoid bias caused by particle bounce. A summary of a recent survey is presented, in which members were asked to provide information about their impactor type and coating methodology, including the composition of the coating material applied to the collection surfaces. There is no standard approach in terms of either materials used or method of applying the coating. However, standardization is unnecessary, since each organization has independently selected and validated their procedure with their own formulations. The newcomer can therefore select from a variety of methods to eliminate particle bounce, and at the same time ensure quantitative recovery and assay of the active pharmaceutical ingredient(s). Introduction Coating of the collection surfaces of the cascade impactor with a media that provides a tacky surface is recognized as an appropriate precaution to minimize particle bounce and reentrainment, especially when testing dry powder inhalers (s) [1,2]. Studies with both the Andersen 8-stage impactor (ACI) [3] and Next Generation Pharmaceutical Impactor () [4] indicate that collection surface coating may also be required for some formulations delivered by pressurized metered dose inhaler (pmdi), especially when measurements are being made with a low number of actuations from the inhaler. The table summarizes the coating methods that are currently in use by members of. Impactor Collection Surface Coating Methods ACI Andersen 8-stage impactor, MMI Marple-Miller impactor, Next Generation Pharmaceutical impactor, VHC valved holding chamber

2 Table 1. Coating Methods Used by Organizations 1 ACI pmdi 2 ACI 3 ACI, 4 ACI pmdi & 5 ACI pmdi, or Aluminium alloy 6 ACI, 7 ACI, 8 ACI, pmdi, Ethanolic solution of Brij35 (polyoxyethylenelaurylether) is mixed with glycerol 11% polypropylene glycol in Hexane A solution of Brij, glycerol and ethanol (ethanol evaporates after applying, before analysis) Glycerol or Brij 35. Applied only if required 1 ml of Brij 35 in 20 ml ethanol dissolved in 5 g glycerol n-hexane + 1% of SPAN 85 (sorbitan trioleate) 1% w/v silicone oil in hexane Dip plate into coating solution, leave in a fume hood to allow solvent to evaporate before assembly of impactor Submerge plate, remove plate allowing the bulk to drain off, then air dry Apply standard amount of coating material (thin) evenly (in practise done with a sponge). Apply standard quantity of solution to give a thin film of coating substance on each plate. Distribute 50 µl per plate For, distribute 100 µl in pre-separator Immerse each plate in a crystalizer containing the coating material. Allow 0.5 hr for solvent evaporation in a fume hood before assembly of impactor Dip plates in solution and allow hexane to evaporate prior to assembly of impactor Inox Glycerine Coat with a thin layer of glycerine

3 9 ACI 10 ACI 11 ACI Liquid systems pmdi, Method 1: Brij 35 (2% w/v) in glycerol Method 2: Span-85 (1% w/v) in hexane 1% soln. Tween20 in methanol. The pre-separator is not coated Non-coated or Brij 35/ethanol 12 ACI Apiezon spray (Dekati Ltd) 13 ACI, 14 ACI, 15 ACI,, pmdi 1% w/v silicone oil in hexane 1% Tween in EtOH alternatively 1% span 85/hexane 3 g Brij 35 P dissolved in 20 ml ethanol, 1 ml of the Brij solution mixed with 5 g glycerol; alternatively: 1 % silicone oil in hexane; alternatively: % Tween80 in glycerol; Dissolve 2.5 g Brij in 25 ml ethanol. Add 4-ml to 20 g glycerol and mix well. Apply 50 µl as coating and spread to coat entire plate surface Apply coating via a pipette, allowing excess to run of plate. Allow solvent to evaporate. Recovery of active by immersion of plate in sample diluent, gently swirling for 10-min Immerse plates, remove and air dry Pipette coating solution onto plate, wipe-off excess and allow to air dry Apply spray to plates once a day (max 6 collections) Dip plates in solution, allowing hexane to evaporate prior to assembly of impactor Dip plates in solution, allow to air dry in clean conditions. Check for homogeneous coating visually before use Distribute 50 µl solution per plate. Distribute 100 µl in pre-separator (ACI) for testing

4 16 ACI,, MMI pmdi/ VHC ACI; metal cups and MMI 17 ACI Aluminium or stainless A check is made for particle bounce at IQ for new impactors or formulations. Coat with a solution of Brij 35, glycerol and ethanol Releasil-B silicone spray (Dow Corning) Apply standard amount of coating material (thin) and evenly. Spray directly on to plate Conclusions The table demonstrates the wide variety of methods that are in current use by members to coat the collection surfaces of cascade impactors for the particle size assessment of a variety of inhaler types. The decision whether or not to coat the collection surfaces of the cascade impactor will depend on both the formulation and type of impactor, and should always be considered as part of the method development process [5]. References 1. USP 26-NF Chapter 601 Physical tests and determinations: Aerosols. United States Pharmacopeia, Rockville, MD, USA European Pharmacopeia Section Preparations for inhalation: aerodynamic assessment of fine particles. European Pharmacopeia: 3 rd Edn., Suppl Council of Europe, Strasbourg, France Nasr, M.M., D.L. Ross and N.C. Miller Effect of drug load and plate coating on the particle size distribution of a commercial albuterol metered dose inhaler (MDI) determined using the Andersen and Marple-Miller impactors. Pharm. Res. 14(10): Kamiya, A., Sakagami, M., Hindle, M. and Byron, P.R Particle sizing with the next generation impactor: A study of Vanceril metered dose inhaler. J. Aerosol Med., 16(2): Christopher D., Curry, P., Doub, B., Furnkranz, K., Lavery, M., Lin, K., Lyapustina, S., Mitchell, J., Rogers, B., Strickland, H., Tougas, T., Tsong, Y. and Wyka, B Considerations for the development and practice of cascade impaction testing, including a mass balance failure investigation tree. J. Aerosol Med. 16: member organizations are: 3M, Astra Zeneca, Aventis, Bespak, Boehringer Ingelheim, Chiesi, Clinical Designs, GlaxoSmithKline, Hovione, Innovata Biomed, Ivax Pharmaceticals, Novartis, Novo Nordisk, Pharmachenie, Pfizer, SkyePharma, Sofotec, Trudell Medical International and Vectura

5 Drug Delivery to the Lungs 14, The Aerosol Society, London, UK, 2003:75-78 PRACTICES OF COATING COLLECTION SURFACES OF CASCADE IMPACTORS: A SURVEY OF MEMBERS OF THE EUROPEAN PHARMACEUTICAL AEROSOL GROUP () J.P. Mitchell on behalf of members of the European Pharmaceutical Aerosol Group members evaluate many different aerosols from both pressurized metered dose inhalers (pmdis) and dry powder inhalers (s) by the use of a cascade impactor. It is widely recognized that pre-coating of particle collection surfaces is a prerequisite in testing to avoid bias caused by particle bounce. A summary of a recent survey is presented, in which members were asked to provide information about their impactor type and coating methodology, including the composition of the coating material applied to the collection surfaces. There is no standard approach in terms of either materials used or method of applying the coating. However, standardization is unnecessary, since each organization has independently selected and validated their procedure with their own formulations. The newcomer can therefore select from a variety of methods to eliminate particle bounce, and at the same time ensure quantitative recovery and assay of the active pharmaceutical ingredient(s).