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 […]
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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), […]
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 […]
The FDA’s Draft Guidance for Industry, “Metered Dose Inhaler (MDI) and Dry Powder Inhaler (DPI) Products – Quality Considerations” released in April 2018, discusses quality attributes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) […]
A key objective of this article is to guide the newcomer to the field, as well as those with familiarity of the topic. Four misconceptions are discussed: Misconception 1: Impactor-sized mass (ISM) always includes data from all impactor stages; Misconception 2: Geometric standard deviation (GSD) is always suitable as the measure of spread of a […]
INFORM2020 is a five-year collaboration of academia and industry to investigate critical parameters that influence the performance of dry powder inhaled (DPI) formulations. In part, the collaboration has been attempting to shed light on key questions through X-ray microscopy, which can offer new insights into the microstructure of inhalable formulations for DPIs. The article also […]
In Parts I and II of this series, we introduced the concept that the batch release criteria for OIPs can and should dictate the quality constraints on all cascade impactors (CIs) used for batch release testing. This logical proposition applies to the entire set of analytical equipment involved in the making and testing of a […]
The authors suggest that impaction data is fundamentally flawed and ineffective because individual stage groupings do not adequately account for both dimensions of the size-fractionated mass comprising the APSD, and their combined use compounds this weakness to dramatic effect. Clearly, they say, stage groupings cannot be relied upon for batch-disposition decisions and are therefore a […]
Synchrotron X-rays can provide valuable quantitative information on drug distribution, spray density, droplet and particle properties; metrics that are difficult or virtually impossible to obtain by other means. Unlike many traditional measurement techniques, synchrotron measurements can provide direct evidence of the effects of changes to actuator design and formulation composition on the behavior of a […]