• December 1, 2023

In the first article, we explored the robustness of the pharmacopeial methodology for the determination of delivered dose uniformity (DDU) for orally inhaled products to bias in volumetric flow rate setting from variations in ambient pressure. In this article, we extend the analysis to evaluate how the determination of the second performance-related critical quality attribute, […]

  • October 17, 2023

In 2020 and 2021, Inhalation published three articles by the Cascade Impaction Working Group of the International Pharmaceutical Aerosol Consortium for Regulation and Science (IPAC-RS): (1) The liability of fine particle dose (FPD); (2) Cascade impactor stage groupings: Poor decisions from degraded data; and (3) Efficient data analysis (EDA): Size, mass and common sense. In […]

  • August 10, 2023

The article describes a series of in vitro test methods that can be used to estimate the total and regional lung doses. The focus of the discussion is on research and development, with the view that the ability to estimate total and regional lung deposition is essential in the design of efficient orally inhaled products. […]

  • April 7, 2023

Much improvement has taken place in evaluating sources of variability in the measures of delivered dose uniformity (DDU) and aerodynamic particle size distribution (APSD). Methods described in the United States Pharmacopeia (USP) and European Pharmacopoeia (Pharm. Eur.) now include dimensions and diagrams for all components critical to their robustness. However, we show that there are […]

  • August 14, 2022

CFD modeling for product development requires knowledge of the capabilities of state-of-the-art software and the adoption of a well-controlled simulation workflow. This article will review previous work in this area, illuminating CFD capabilities and the processes and considerations required to create a trusted, useful, predictive simulation to support the product development process. This article shows […]

  • April 8, 2022

Considering flow conditions in the DPI test system has led to understanding more about why experts have improved the pharmacopeial protocol over time. Still, there are aspects of the fundamentals that are not yet clarified but worth understanding and accommodating in the protocols. The authors believe these include specifications for the solenoid valve, the effect […]

  • December 7, 2021

Impaction-based methods for determining the aerodynamic particle size distributions (APSDs) of aerosolized drug products intended for oral and nasal inhalation are preferred by regulatory authorities because they can be used to directly classify the APSD in terms of the drug substance content of the sampled drug product. One such impactor, the Next Generation Impactor (NGI), […]

  • August 10, 2021

Production of inhalable drug particles traditionally involves milling, spray drying, spray freeze drying and supercritical fluid processes. Many of these processes expose the formulation to thermal or mechanical stresses, leading to changes in the particles’ surface and physicochemical properties. Among various particle properties (particle size and size distribution, surface properties, hygroscopicity, electrostatic charge and relative […]

The authors believe that the decision-making framework used to demonstrate product quality consists of both the metrics themselves and the way they are used to make the decision. In the context of inhaler APSD, they contend that good decision-making requires independent assessments of each dimension of the APSD, namely size and mass, which they propose […]

  • June 9, 2021

The FDA’s Draft Guidance for Industry, “Metered Dose Inhaler (MDI) and Dry Powder Inhaler (DPI) Products – Quality Considerations” released in April 2018, discusses quality attributes for metered dose inhalers (MDIs) and dry powder inhalers (DPIs). Regardless whether pursuing innovator or generic product development, the importance of establishing a desired quality target product profile (QTPP) […]