The therapeutic benefits of metered dose inhalers (MDIs) in pulmonary disorders are mainly driven by aerosol performance, which depends on formulation variables (drug and excipients), device design, and patient interactions. The present study provides a comprehensive investigation to better understand the effect of formulation variables on mometasone furoate (MF) suspension-based MDI product performance. The effects of MF particle size (volume median diameter; X) and excipient concentration (ethanol and oleic acid, cosolvent, and surfactant, respectively) on selected critical quality attributes (delivered dose (DD), fine particle dose of particles lesser than 5 µm (FPD < 5), ex-throat dose and median dissolution time (MDT)) were studied.
View Article and Find Full Text PDFWhile first introduced in the 1950s, pressurized metered dose inhalers (pMDIs) remain as a first line treatment of pulmonary conditions. With expanding applications of pMDIs beyond asthma and chronic obstructive pulmonary disease (COPD), the development of therapies utilizing the pMDI platform will undoubtedly continue. Recent guidances and the introduction of quality by design initiatives further emphasize the requirement of formulators to understand the relationships between product attributes and production strategies and their impact on product performance.
View Article and Find Full Text PDFThe performance of pressurized metered dose inhalers (MDIs) is affected by formulation and device variables that impact delivered dose, aerodynamic particle size distribution, and consequently lung deposition and therapeutic effect. Specific formulation variables of relevance to two commercially available products-Proventil® HFA [albuterol sulfate (AS) suspension] and Qvar® [beclomethasone dipropionate (BDP) solution]-were evaluated to determine their influence on key performance attributes measured experimentally with in vitro cascade impaction studies. These commercial MDIs, utilized as model systems, provided mid-points for a design of experiments (DoE) plan to manufacture multiple suspension and solution MDI formulations.
View Article and Find Full Text PDFPressurized metered dose inhalers (pMDIs) are widely used for the treatment of pulmonary diseases. The overall efficiency of pMDI drug delivery may be defined by in vitro parameters such as the amount of drug that deposits on the model throat and the proportion of the emitted dose that has particles that are sufficiently small to deposit in the lung (i.e.
View Article and Find Full Text PDFMetered dose inhalers (MDIs) are complex drug-device combination products widely used to treat pulmonary disorders. The efficacy, driven by aerosol performance of the products, depends on a multitude of factors including, but not limited to, the physicochemical properties of drug and nature and amount of excipient(s). Under the quality by design (QbD) paradigm, systematic investigations are necessary to understand how changes in critical quality attributes (CQAs) of formulation, device, and manufacturing process influence key product performance parameters, such as delivered dose (DD) and fine particle dose (FPD).
View Article and Find Full Text PDFA simulation model has been established to predict the residual aerodynamic particle size distribution (APSD) of dual-component pressurized metered dose inhalers (pMDIs). More specifically, this model estimates the APSD of pMDI formulations containing dissolved and suspended compounds for various formulations, and has been verified experimentally. Simulated and experimental data illustrate that APSDs of the dissolved and suspended components of the pMDI are influenced by concentrations of the dissolved and micronized suspended drugs, along with suspended drug size.
View Article and Find Full Text PDFPressurized metered dose inhalers (pMDIs) are frequently used for the treatment of asthma and chronic obstructive pulmonary disease. The aerodynamic particle size distribution (APSD) of the residual particles delivered from a pMDI plays a key role in determining the amount and region of drug deposition in the lung and thereby the efficacy of the inhaler. In this study, a simulation model that predicts the APSD of residual particles from suspension pMDIs was utilized to identify the primary determinants for APSD.
View Article and Find Full Text PDFAnn Allergy Asthma Immunol
July 2014
Background: The selection of accessory devices for pressurized metered-dose inhalers (pMDIs) by health care professionals is typically cost driven without consideration of how the device modifies clinical outcomes.
Objective: To evaluate nonconventional accessory devices and the open-mouth technique with and without ideal coordination of actuation and inhalation to identify and understand the considerations for recommending potential inexpensive devices.
Methods: In vitro performance parameters of the beclomethasone dipropionate pMDI were evaluated with several devices (AeroChamber, toilet paper roll, paper towel roll, rolled paper, plastic bottle spacer, bottle-holding chamber, and nebulizer reservoir tubing).
Pressurized metered dose inhalers (MDIs) are a long-standing method to treat diseases of the lung, such as asthma and chronic obstructive pulmonary disease. MDIs rely on the driving force of the propellant, which comprises the bulk of the MDI formulation, to atomize droplets containing drug and excipients, which ideally should deposit in the lungs. During the phase out of chlorofluorocarbon propellants and the introduction of more environmentally friendly hydrofluoroalkane propellants, many improvements were made to the methods of formulating for MDI drug delivery along with a greater understanding of formulation variables on product performance.
View Article and Find Full Text PDFPressurized metered dose inhalers (MDIs) were first introduced in the 1950s and they are currently widely prescribed as portable systems to treat pulmonary conditions. MDIs consist of a formulation containing dissolved or suspended drug and hardware needed to contain the formulation and enable efficient and consistent dose delivery to the patient. The device hardware includes a canister that is appropriately sized to contain sufficient formulation for the required number of doses, a metering valve capable of delivering a consistent amount of drug with each dose delivered, an actuator mouthpiece that atomizes the formulation and serves as a conduit to deliver the aerosol to the patient, and often an indicating mechanism that provides information to the patient on the number of doses remaining.
View Article and Find Full Text PDFPressurized metered dose inhalers (pMDIs) are widely used for the treatment of diseases of the lung, including asthma and chronic obstructive pulmonary disease. The mass median aerodynamic diameter of the residual particles (MMADR) delivered from a pMDI plays a key role in determining the amount and location of drug deposition in the lung and thereby the efficacy of the inhaler. The mass median diameter of the initial droplets (MMDI), upon atomization of a formulation, is a significant factor influencing the final particle size.
View Article and Find Full Text PDFA new model has been developed for predicting size distributions delivered from pressurized metered dose inhalers (pMDIs) that contain suspended drug particles. This model enables the residual particle size distribution to be predicted for a broad range of formulations. It expands on previous models by allowing for polydisperse micronized input drug, multiple suspended drugs, dissolved drug, and dissolved or suspended excipient to be included in the formulation.
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