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. […]
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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 […]
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 […]
A large gap exists between the relatively straightforward robust methods in the pharmacopeias, developed primarily for product release, and the more elaborate approaches to assist in understanding how inhalers are likely to perform in the hands of the patient or caregiver. The authors propose that there is a middle way forward and believe it is […]
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), […]
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 […]
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 […]
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 […]
Studies characterizing the toxicity of drugs (and, ideally, non-clinical efficacy studies) dose animals via the most clinically relevant route. While oral or injected dosing of animals is straightforward, inhaled administration of drugs presents technical and logistical challenges. This article provides an overview of considerations and industry practices for performing non-clinical studies in support of inhaled […]
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 […]