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almost identical to its European Pharmacopoeial coun- terpart. 4 e driving force was the realization that there had been little guidance in either of the pharmacopeias concerning quality testing of the widespread aqueous formulations available for use with nebulizing systems not linked with a specific drug product. Chapter <1601> is comprised of two aspects of perfor- mance testing for nebulized products: 1. Drug substance delivery rate and total drug substance delivered per dose; 2. Aerodynamic assessment of nebulized aerosols. ese tests are analogous to the evaluation of delivered dose uniformity (DDU) and aerodynamic particle size distribution (APSD) in Chapter <601>. It is important to keep in mind that these tests standardize the approach for the assessment of the dose that would be delivered to a patient, but are not intended to provide an assessment of a given nebulizer device. Current International Standard ISO 27427:2013 covers nebu- lizer device testing and includes aspects that relate to the design verification of the device. It also discusses situa- tions in which any solution containing drug product or a non-pharmaceutical tracer compound, such as sodium fluoride, can be used for that purpose. 5 Nebulizers are commonly used by patients of all ages who are tidally breathing. e drug substance delivery rate and total drug substance delivered are therefore measured with the mouthpiece of the nebulizer con- nected to a breathing simulator via an aerosol filter (Fig- ure 2). Adult breathing patterns (Table 1) were taken from a pre-existing European Standard, 6 while pediatric simulation breathing patterns were derived from a Canadian Standard. 7 Figure 1 USP–NF General Chapters within the responsibility of the Aerosols Sub-Committee. Chapters shaded in green are official and chapters shaded in orange are in preparation for publication as Official Text through the Stimuli article process in Pharmacopeial Forum. APSD = aerodynamic particle size distribution; DDU = delivered dose uniformity. NORMATIVE CHAPTERS <601> INHALATION AND NASAL DRUG PRODUCTS: AEROSOLS, SPRAYS, AND POWDERS —PERFORMANCE QUALITY TESTS <602> PROPELLANTS <603> TOPICAL AEROSOLS <604> LEAK RATE <5> INHALATION AND NASAL DRUG PRODUCTS — GENERAL INFORMATION AND PRODUCT QUALITY TESTS INFORMATIVE CHAPTERS <1601> PRODUCTS FOR NEBULIZATION <1602> SPACERS AND VALVED HOLDING CHAMBERS USED WITH INHALATION AEROSOLS — CHARACTERIZATION TESTS <1603> GOOD CASCADE IMPACTOR PRACTICES (IN DEVELOPMENT) <1604> DATA INTERPRETATION OF APSD MEASUREMENTS FOR ORALLY INHALED PRODUCTS (IN DEVELOPMENT) Table 1 Sinusoidal Tidal Breathing Patterns in USP Chapter <1601> to Determine Drug Substance Delivery Rate and Total Drug Substance Delivered from a Nebulizing System Parameter NEONATE INFANT CHILD ADULT Total Volume (mL) 25 50 155 500 Frequency (breathing cycles/min) 40 30 25 15 Inhalation/ Exhalation Ratio 1:3 1:3 1:2 1:1 Figure 2 Test configuration to determine drug substance delivery rate and total drug substance delivered from a nebulizing system. Nebulizer Aerosol Filter Breathing Simulator Inhalation December 2018 13