Mini reviewDry powder inhalers (DPIs)—A review of device reliability and innovation
Introduction
Dry powder inhalers (DPIs) are devices through which a dry powder formulation of an active drug is delivered for local or systemic effect via the pulmonary route. DPIs have a number of advantages over other methods of pulmonary drug delivery, for example, direct delivery of drug into the deep lungs utilizing the patient's respiration and are increasingly being explored as a mechanism for the delivery of systemic drugs. Successful delivery of drugs into the deep lungs depends on the integration between powder formulations and the device performance (Peart and Clarke, 2001). Licensing and marketing approval requires that current DPIs demonstrate in vitro performance and in vivo efficacy and reliability. However, questions remain about the ability to interchange DPIs and the effects of different clinical states and patient characteristics.
Dry powders for inhalation are formulated either as loose agglomerates of micronised drug particles with aerodynamic particle sizes of less than 5 μm or as carrier-based interactive mixtures with micronised drug particles adhered onto the surface of large lactose carriers (Hersey, 1975). For topical respiratory drug delivery, a particle size of 2–5 μm yields optimal benefit, whereas for systemic effects particle size of less than 2 μm is needed for drug deposition in the small peripheral airways. Particles greater than 5 μm may also result in systemic effects due to impaction in the throat (i.e., oropharyngeal delivery) and oral absorption (Newman and Clarke, 1983; Byron, 1986; Hickey, 1992, Bisgaard, 1996). The powder formulation is aerosolized through a DPI device, where the drug particles are separated from the carrier (from drug–carrier mixtures) or deagglomerates drug particles, and the dose is delivered into the patient's deep lungs. In these systems, particle size and flow property, formulation, drug–carrier adhesion, respiratory flow rate and design of DPI devices extensively influence the performance (Hickey and Concessio, 1997).
Since the inception of the first DPI Spinhaler® (Aventis), device technology has continued to grow and a lot of devices are now currently available on the market; however, no devices have shown remarkable efficiency in delivering drugs from the formulation. Researchers are searching ways to improve the efficiency of drug delivery from DPI by changing formulation technology, designing drugs and carriers and designing new devices. Currently, a large number of DPI devices are on the market, a significant number are awaiting Food and Drug Administration (FDA) approval, some are under development and a large number have been patented and/or applied for patent and have not been perfected. Therefore, the aim of this paper is to determine whether device reliability is more important than innovation. This question can be interpreted in a number of ways. Some may define innovation as the development of an entirely novel system for dry powder inhalation. Others would suggest that it can also mean improvements in existing devices. Therefore, innovation and improvements in device reliability may not be mutually exclusive. For the purposes of this discussion the question has been interpreted as meaning ‘should our research efforts focus on optimising existing DPIs or pursuing the development of novel DPIs?’
This paper discusses factors for consideration in the design of DPIs, limitations in current DPIs, the characteristics of an ideal DPI and recent innovations in powder formulation and inhalation devices. This discussion enables a comparison of the relative merits of optimising existing DPIs or seeking to develop novel devices.
Section snippets
Dry powder inhalers
The aerosolization or inhalation of medicaments by humans has been used since late the 1950s and since 1956, the pressurised metered dose inhaler (pMDI) become the most commonly used device to deliver inhaled asthma drugs (Freedman, 1956); however, with the advancement of science and technology, pulmonary delivery of drugs has become the route of choice after the introduction of the DPI in 1967 (Altounyan, 1967, Bell et al., 1971). Inhalation therapy, or pulmonary drug delivery, via pMDIs, DPIs
The question of device reliability vs. innovation
Bryan (2005) recently posed the question of where should researchers focus their efforts in the development of delivery systems for pulmonary drug administration. It is clear that many pharmaceutical companies are asking this question and will continue to explore the options, particularly given the considerable size of the existing and future potential markets. However, the major limitation for the development of a truly innovative product is cost and therefore Bryan provides a strong argument
Discussions and conclusion
This review article sought to examine whether device reliability is more important than innovation. With the advancement of science and technology, this problem needs to be addressed in the changing world. Pulmonary drug delivery is a promising route of administration as it is non-invasive and helps patient compliance.
Despite appropriate standards of device reliability being a requirement for licensing and marketing of DPIs, there remain areas for improvement. Innovation and improvements in
Acknowledgement
The authors greatly appreciate Christy Noble for proof reading this article and thoughtful suggestions.
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