Method for assessing the efficacy of an aerosol for pulmonary drug delivery as well as inhaler device, orally inhaled and/or nasal drug product and drug/device combination product
Inventors
Biehler, Jonas • Wichmann, Karl-Robert Klaus • Müller, Kei Wieland • Rudlstorfer, David • Grill, Maximilian Josef • RICHTER, Jakob
Assignees
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Publication Number
US-12357775-B2
Publication Date
2025-07-15
Expiration Date
Abstract
The invention relates to systems and methods for assessing the efficacy of an aerosol for pulmonary drug delivery as well as to an inhaler device, an orally inhaled drug product and a drug/device combination product. An aerosol can be generated by an inhaler device and comprises aerosol particles containing an orally inhaled drug product. The method comprises the steps of providing a computational lung model and a computational particle transport and deposition model, computing a spatial particle deposition distribution of discrete particles based on a determined aerosol value of an aerosol parameter, computing an efficacy value of an efficacy parameter based on the spatial particle deposition distribution and using the efficacy value for automatically assessing the efficacy for pulmonary drug delivery of the aerosol.
Core Innovation
The invention provides a method for assessing efficacy of an aerosol for pulmonary drug delivery, where the aerosol comprises aerosol particles containing an orally and/or nasally inhaled drug product. The method determines at least one aerosol value of at least one aerosol parameter characterizing the aerosol and models a respiratory system structure and transient gas flow in airways between trachea and lungs during inhalation and/or exhalation.
The method further determines a computational particle transport and deposition model representing transient transport of individual aerosol particles in the transient gas flow in the airways and deposition of the individual aerosol particles in the respiratory system. Based on the aerosol value(s), using the computational lung model and the computational particle transport and deposition model, the method determines a spatial particle deposition distribution of a plurality of discrete particles representing the aerosol particles deposited in the respiratory-system structure.
Finally, the method determines at least one efficacy value of an efficacy parameter indicating efficacy of pulmonary drug delivery based on the spatial particle deposition distribution. The framework also supports determining efficacy using computational absorption/pharmacokinetic modeling, producing concentration- and dose-related efficacy metrics derived from deposition, including time-dependent concentrations and values such as AUC, T_max, retention, and selectivity.
Claims Coverage
The independent claims cover four categories of subject matter: a method for assessing pulmonary drug-delivery efficacy from aerosol values and computational deposition, a computing system implementing the same workflow, a non-transitory computer-readable storage medium implementing the workflow, and a drug/device combination product whose inhaler and drug product are determined at least in part by the claimed operations. Across these claims, the core inventive features include determining aerosol values, modeling transient airway gas flow in a computational lung model, modeling transient transport and deposition of discrete aerosol particles, computing a spatial particle deposition distribution, and determining an efficacy value based on that distribution.
Determining aerosol value characterizing the aerosol and modeling airway transient gas flow
Determining at least one aerosol value of at least one aerosol parameter characterizing an aerosol; determining a computational lung model representing a structure of a respiratory system and transient gas flow in airways at least between trachea and lungs, the transient gas flow being modeled during inhalation and/or exhalation.
Computational particle transport and deposition for individual discrete aerosol particles
Determining a computational particle transport and deposition model representing transient transport of individual aerosol particles in the transient gas flow in the airways and deposition of the individual aerosol particles in the respiratory system; determining a spatial particle deposition distribution of a plurality of discrete particles representing aerosol particles deposited in the structure of the respiratory system based on the at least one aerosol value using the computational lung model and the computational particle transport and deposition model.
Efficacy value from an efficacy parameter based on spatial deposition distribution
Determining at least one efficacy value of an efficacy parameter indicating efficacy of pulmonary drug delivery of the aerosol based on the spatial particle deposition distribution.
System configured to execute efficacy assessment operations
A system comprising at least one memory storing instructions and at least one processor configured to execute the instructions to perform operations comprising determining at least one aerosol value, determining a computational lung model with transient gas flow between trachea and lungs, determining a computational particle transport and deposition model for transient transport and deposition of individual aerosol particles, determining a spatial particle deposition distribution, and determining at least one efficacy value based on the spatial particle deposition distribution.
Non-transitory computer-readable storage medium executing efficacy assessment operations
A non-transitory computer-readable storage medium encoded with computer readable instructions, which, when executed by a processor, executes operations comprising determining at least one aerosol value, determining a computational lung model with transient gas flow between trachea and lungs, determining a computational particle transport and deposition model for transient transport and deposition of individual aerosol particles, determining a spatial particle deposition distribution, and determining at least one efficacy value based on the spatial particle deposition distribution.
Drug/device combination product with aerosol efficacy determined by the claimed operations
A drug/device combination product comprising an inhaler device and orally and/or nasally inhaled drug product, the orally and/or nasally inhaled drug product having been determined at least in part by operations comprising determining at least one aerosol value, determining a computational lung model with transient gas flow between trachea and lungs, determining a computational particle transport and deposition model for transient transport and deposition of individual aerosol particles, determining a spatial particle deposition distribution, and determining at least one efficacy value based on the spatial particle deposition distribution.
Computational lung model based on processed image data from a single tomographic image
A system configured to execute operations comprising determining at least one aerosol value, determining a computational lung model representing a structure of a respiratory system and transient gas flow between trachea and lungs, the computational lung model being based on a discretized respiratory-system structure derived from processed image data of a single tomographic image, determining a computational particle transport and deposition model for transient transport and deposition, and determining a spatial particle deposition distribution of a plurality of discrete particles based on the at least one aerosol value.
Computational lung model based on discretized individual or averaged processed image data
A system configured to execute operations comprising determining at least one aerosol value, determining a computational lung model representing a structure of a respiratory system and transient gas flow between trachea and lungs, wherein the computational lung model is based on a discretized individual respiratory-system structure derived from processed image data representing an individual respiratory system, or a discretized averaged respiratory-system structure derived from processed image data representing an average of a plurality of respiratory systems, determining a computational particle transport and deposition model for transient transport and deposition, and determining a spatial particle deposition distribution based on the at least one aerosol value.
Computational lung model based on healthy respiratory system and predetermined pathological image-data patterns
A system configured to execute operations comprising determining at least one aerosol value, determining a computational lung model representing a structure of a respiratory system and transient gas flow between trachea and lungs, wherein the computational lung model is based on a discretized respiratory-system structure derived from processed image data representing at least one healthy respiratory system and at least one predetermined pathological image-data pattern representing a pathological modification of at least one zone of the respiratory system caused by a lung disease, determining a computational particle transport and deposition model for transient transport and deposition, and determining a spatial particle deposition distribution based on the at least one aerosol value.
Computational inhaler device model for determining aerosol values from inhaler design parameters
Determining at least one aerosol value of at least one aerosol parameter characterizing an aerosol, the at least one aerosol value determined using a computational inhaler device model representing flow of the aerosol in an inhaler device, wherein the computational inhaler device model represents at least one component of the inhaler device characterized by at least one device design parameter, and wherein the at least one device design parameter is indicative of one or more of a shape of a mouth piece and/or ventilation tubing, a diameter and/or shape of a nozzle, a flow channel geometry from an outlet of an aerosol generation and/or aerosol storage chamber to an outlet, and a volume and/or geometry of a canister.
Across the independent claims, efficacy of pulmonary drug delivery is determined from a computational workflow: determine at least one aerosol value, model transient gas flow in a computational lung model between trachea and lungs, simulate transient transport and deposition of individual aerosol particles, compute a spatial particle deposition distribution, and then determine an efficacy value of an efficacy parameter based on that deposition distribution. Independent variants further specify implementation in a system or computer-readable medium, support a drug/device combination product whose formulation is determined at least in part by the operations, and refine the computational lung model basis using processed image data and determining aerosol values via a computational inhaler device model parameterized by inhaler design parameters.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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