Using Filters to Estimate Regional Lung Deposition with Pressurized Metered Dose Inhalers.

PURPOSE: To evaluate the suitability of a recently proposed apparatus that uses filters to directly fractionate the in vitro lung dose into regional deposition estimates for use with pressurized metered dose inhaler (pMDI) devices as a less resource intensive alternative to cascade impaction. METHODS: Using three commercially available pMDI devices (Asmanex HFA, Ventolin HFA, QVAR), regional deposition estimates were measured directly using the filter-based apparatus (FBA). Regional deposition estimates were also generated for the same inhalers by performing cascade impaction measurements and inputting the results to an in silico regional deposition model. Regional deposition for each inhaler was evaluated at an inhalation flow rate of 30 and 60 L/min. RESULTS: Total recovery of active pharmaceutical ingredient and extrathoracic deposition was independent of method used. The regional deposition estimates provided by each method were similar and captured the same trends. CONCLUSIONS: The direct measurement of estimated regional deposition is possible when using the FBA. This method is far less resource intensive than existing methods and so may be useful both for comparison of generic alternatives and the development of innovative products.

Spray Pattern and Plume Geometry Testing and Methodology: An IPAC-RS Working Group Overview.

Plume characterization for orally inhaled and nasal drug products (OINDP) provides valuable information during OINDP development. Spray pattern and plume geometry techniques, methods, and technology have evolved over the past 20 years since the publication of the original 1998 FDA MDI DPI draft guidance. The International Pharmaceutical Aerosol Consortium on Regulation and Science (IPAC-RS) discusses the historical context and background to plume geometry and spray pattern characterization studies; provides an analysis of the current regulatory context; addresses results from its industry surveys on application and value of such testing; and presents case studies and best practices-seeking to provide insights to regulatory bodies and other stakeholders. Assessment and consideration of published studies and industry experience note the value of plume geometry and spray pattern in development, and that further data is needed regarding their use in assessing formulation characteristics. Continued dialogue between industry and regulatory bodies is needed to establish the optimum use of these techniques.

Using Filters to Estimate Regional Lung Deposition with Dry Powder Inhalers.

PURPOSE: To develop an in vitro method to rapidly evaluate regional lung doses delivered by pharmaceutical inhalers. Currently, cascade impactor measurements are used, but these are resource intensive and require significant post processing of in vitro data to arrive at regional deposition estimates. METHODS: We present a specialized filter apparatus that mimics tracheobronchial (TB) deposition of pharmaceutical aerosols emitted by commercially available dry powder inhalers (DPIs). The filter housing includes an electrostatic neutralizer to eliminate artificial electrostatic filtration effects. Regional deposition (tracheobronchial and alveolar) for four DPIs (Onbrez Breezhaler, Flovent Diskus, Pulmicort Turbuhaler, and Asmanex Twisthaler) was estimated using cascade impactor measurements and an in silico regional deposition model. These estimates were compared to direct measurements of regional deposition as provided by the TB filter mimic and an absolute filter placed downstream of the TB filter housing, representing the alveolar dose. RESULTS: The two methods were shown to provide similar estimates of extrathoracic, tracheobronchial, and alveolar deposition, as well as total recovery of active pharmaceutical ingredients. CONCLUSIONS: Because of its design, the TB filter apparatus makes it possible to estimate regional deposition with inhalers directly using variable inhalation profiles without any additional equipment or changes to the experimental configuration. This method may be useful to expedite development of both innovative and generic drug products as it provides regional respiratory tract deposition estimates using fewer resources than exisiting methods.

Simulating the effect of individual upper airway anatomical features on drug deposition.

This study aims to systematically isolate different anatomical features of the human pharynx with the goal to investigate their independent influence on airflow dynamics and particle deposition characteristics in a geometrically realistic human airway. Specifically, the effects of the uvula, epiglottis and soft palate on drug particle deposition are studied systematically, by carefully removing each of these anatomical features from reconstructed models based on MRI data and comparing them to a benchmark realistic airway model. Computational Fluid Dynamics using established turbulence models is employed to simulate the transport of mono-dispersed particles (3 µm) in the airway at two flow-rates. The simulations suggest three findings: 1) widening the space between the oral cavity and oropharynx and where the soft palate is situated leads to the most dramatic reduction in drug deposition in the upper airway; 2) exclusion of the uvula and epiglottis: a) affects flow dynamics in the airway; b) alters regional deposition behaviour; c) does not significantly affect the total number of particles deposited in the pharynx; and 3) the space adjacent to the soft palate is a key determinant for aerosol deposition in the extrathoracic region and is related to mechanisms of flow acceleration, diversion and recirculation.

Personalizing aerosol medicine: development of delivery systems tailored to the individual.

Inhalation of drugs for therapeutic effects is not a recent innovation as illicit drugs have been 'smoked' for millennia. Nicotine delivery 'devices' in convenient packaged cartons of cigarettes are simple to use, inexpensive per dose and accessible to people of most ages and lung function, but of course their use leads to increased cancer, emphysema, heart disease and other medical and societal problems. In contrast, many inhalation pharmaceutical medical devices are expensive, nonportable, inconvenient, and/or are used improperly thus leading to poor therapeutic benefit. We review the current state of the art with respect to aerosol delivery, inhalation devices and the ability to personalize the treatment and management of lung disease. The confluence of many drivers will lead to more programmable and flexible devices in the future: the transition from the blockbuster model to customized therapy, technological advancements (e.g., smartphones) and cultural changes including social networking.