inhalation

The introduction of new routes of delivery combined with increasing research and development efforts, a competitive landscape, and a larger market for therapy, have resulted in many new market opportunities for drug delivery devices. In this precise case, advances in drug formulation and inhalation device design, are creating new opportunities for inhaled drug delivery as an alternative to oral and parental delivery methods.

The global market for asthma and chronic obstructive pulmonary disease (COPD) prescription drugs was valued at $34.9 billion in 2011. This figure is projected to reach $38 billion in 2012 and $47.1 billion in 2017, increasing at a fiveyear compound annual growth rate (CAGR) of 4.4%. (BCC  Research)

A growing focus on pediatric and geriatric markets around the world has forced pharmaceutical companies to develop more convenient drug formulations, thereby enhancing overall compliance.

Much of the interest in pulmonary delivery of systemic drug therapies is focused on chronic diseases and refractory conditions. Pulmonary delivery of drugs for the treatment of respiratory diseases stems from the fact that topical drug deposition to the infected lung gives a fast therapeutic effect and reduces side effects associated with key drugs.

Respiratory conditions such as asthma, chronic obstructive pulmonary, and emphysema disease are classical therapeutic areas of the pulmonary sector. However, recent technological advancements have applied the application of pulmonary delivery devices to the treatment of nonrespiratory conditions.

The inhalation systems market, comprising DPIs and MDIs, is forecast to grow by up to two digit percentage per year until 2016, especially in volumes. Key factors are driving growth, such as the increasing incidence of pulmonary diseases or an increasing awareness of the inherent benefits offered by the pulmonary route for systemic drug delivery.

DPI’s represent the most rapidly expanding field in pulmonary drug delivery as a result of perceived limitations in pMDI’s and nebulizers following advantages in their design and performance, including being very portable, patient friendly with ease of use and not requiring spacers.

BeyonDevices knows that the inhalation device is an important factor in achieving adequate delivery of inhaled products to the lungs, therefore a number of characteristics are important for device reliability, clinical efficacy and patient acceptance. With this in mind BeyonDevices devised a DPI platform with a focus on ease of use, flexible, inexpensive production and portability while considering an environment where the drug can maintain its stability and producing reproducible dose dosing.

By choosing a capsule format DPI, BeyonDevices efficiently addressed the issues concerning storage stability and protection against external agents, while ensuring consistency in dose delivery throughout the life of the inhaler. This also means that the powder formulation can change since it’s packed inside the capsule, without the need for any major change in the basic design of the DPI. For the pharmaceutical manufacturer this translates in rapid development ideal for combination products, simple and standard manufacturing process, cost-effective solutions and a process that is environmentally sustainable.

velocity magnitude

Contour of velocity magnitude inside BeyonDevices DPI.

A capsule based Dry Powder Inhaler (DPI) is a breath-actuated device that is triggered by the patient’s inspiratory fow to dispense a dry powder formulation and deliver the fne particle drug fraction to the lungs. Defnition of DPI geometry is critical in the development of effcient delivery devices. Assessment and optimization of the geometry has traditionally used empirical approaches however, simulation technologies are required to streamline the development as well as to gain substantial product understanding serving internal and external customers within their product development activities.

BeyonDevices’ objectives of using CFD includes computing the velocity field and pressure distribution inside the inhaler, evaluating the impact of the inlet shape in inhaler performance and assessing model performance as a function of different parameters regarding subsequent studies.

 

BeyonDevices DPI is designed with simplicity in mind. This simplicity is helpful both to patient and health practitioners alike since they are training patients to use the devices correctly.

In terms of potential benefits for the patient we look to a solution delivering a higher percentage of drug dose to the lung while less drug is deposition in the pulmonary route.

The final product design is focusing on enhancing compliance through small, ergonomic and simple to use solutions, allowing patients to use it properly. The fact we are developing a capsule-based DPI means that breath actuation of the device helps eliminate the coordination issues that occur with other type of inhalers.

Our DPI development focus on providing our clients with a high efficiency in delivering the drug – meaning the use of less drug and increase savings. Other cost savings come from a simple design with fewer parts. Our DPI innovative system provides flexibility in the use of different formulations being available in multiple configurations to meet the needs of each individual application.

During the development of the device design we are focusing on providing protection from moisture ingress while still maximizing the transfer of energy from the user inhalation to the drug formulation in the capsule. Here we pay special attention to the response to low rate profiles on product performance, representative of senior, children and chronically ill patients.

inhalers

BeyonDevices devised a DPI platform with a focus on ease of use, flexible, inexpensive production and portability while providing an environment where the drug can maintain its stability and producing reproducible dose dosing.

The design of BeyonDevices DPI is developed in such a way that the device design should induce sufficient turbulence and particle-particle collisions to detach drug particles from the carrier surface in interactive mixtures/formulations or deagglomerating particles from large agglomerates of drugs-only formulations. By selecting a unique piercing mechanism to prepare the dose within the capsule for fluidization with tangential flow of air during patient inspiration, BeyonDevices DPI addresses the challenge of different formulations needing different air flow properties within the DPI to adequately aerolise fine particles in order to deliver drugs into the deep lungs. The device body is therefore designed in a way to consistently deliver a high fine particle fraction (FPF) of drugs from different formulations.

The mechanism of piercing the capsule it its unique innovative advantage in its “engine” design/mode of action - introducing specifically designed cannulas to perforate the capsule and provide a controllable air flow - therefore addressing the most difficult requirement from all formulation/drug companies: suitability of usage across a with range of drugs/formulations and doses by easily changing tangential air flow parameters without a need for a total DPI redesign.

Further by being able to produce a cost-effective device with a reduced number of parts BeyonDevices DPI platform can develop into a very attractive disposable device that will overcome the needs for cleaning the device, concerns about product stability and being less expensive with improved patient compliance.

BeyonDevices is the first DPI developer that specifically addresses the two main approaches used to improve the performance characteristics of DPI’s - either focusing on a better device or on a better formulation - in a novel combined way.

We also incorporate into its development process the know-how of market-leading partners from the industry in formulation and capsule manufacturing, therefore focusing on achieving the best performance – always with the patient needs in mind.

The BeyonDevices DPI platform benefits:

  • Flexibility - the design and reduced number of components/pieces has incorporated all the current and future trends in this discipline - like combined dosage used for combination drugs
  • Optimized capsule performance and specification: both for physical characteristics and interaction with a large number of formulations; for the first time the capsule development is custom engineered in coordination with both formulation, DPI and addressing regulatory requirements
  • Unique piercing mechanism: using cannulas instead of lancets brings the possibility for optimization of air flow through and within the capsule, therefore potentiating the use on novel formulations
  • Direct control of air flow properties: the capsule perforation mechanism is controlling the flow properties according to formulation requirements as well as inspiratory flow rates, focusing on deep lung delivery of the novel particle/drug - a radically new concept
  • Device performance can be easily adapted to optimize performance across a range of flow rates to account for all possible patients and clinical circumstances • Minimal interaction between drug formulation and device: the capsule is the main compartment for storage and disaggregation of particles while cannulas deliver the air flow directly to the DPI mouth piece

BeyonDevices DPI is currently undergoing extensive in vitro testing for the optimization of flow and turbulence characteristics for specific initial set-ups of the capsule perforating mechanism. By combining this information with results from our in-house developed CFD simulations we are creating a working platform that offers the potential of early optimization of the device performance to a specific formulation.

In addition to this testing for performance evaluation BeyonDevices is adding new capabilities to the platform by introducing the first results of its program for “smart packaging”, such as the capacity to collect usage and performance data and transmit it to other electronic platforms.

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BeyonDevices is a pioneer in the use of computational fluid dynamics (CFD) for the optimization of device parameters during early stages of DPI development. CFD is used to model the inhalation flow stream, pressure profiles and ultimately particle trajectories.

Coupling CFD simulations with in vitro device and aerosol performance provides important information on the relative contributions of device geometry and formulation for the deagglomeration of particle complexes.

BeyonDevices development methodology uses CFD to look at alterations in device geometry (air inlet area, mouthpiece length) and operating parameters (volumetric flow rate, capsule size) in order to study the flow field and assess carrier particle trajectories within the DPIs during actuation and understand and assess their influence on in vitro aerosol performance.

This unique coupling of experimental and in vitro data allows for a better understanding of the factors that will have an important influence in the optimization of the DPI performance with a specific formulation.

This service is also available from BeyonDevices for development of new DPI geometries or evaluation of existing ones with different formulations.