Mini review
Dry powder inhalers (DPIs)—A review of device reliability and innovation

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Abstract

A wide range of dry powder inhaler (DPI) devices are currently available on the market to deliver drugs into lungs with a view to maximise drug delivery with low variability. DPIs also face numerous clinical challenges, particularly related to variable patient factors such as age, clinical condition and inspiratory flow. Due to the drug formulation and the design of devices, different DPIs do not show the same performance and manufacturers are taking a variety of device design approaches. The characteristics of an ideal DPI, recent innovations in powder formulation and device design are not universally reliable in terms of dose variability, clinical efficacy, user friendliness and economy. This mini review examines whether device reliability is more important than innovation. This study enables a comparison of the relative merits of optimising existing DPIs or seeking to develop novel devices.

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.

References (152)

  • D.L. French et al.

    The influence of formulation on emission, deaggregation and deposition of dry powders for inhalation

    J. Aerosol Sci.

    (1996)
  • M. Friede et al.

    Need for new vaccine formulations and potential of particulate antigen and DNA delivery systems

    Adv. Drug Deliv. Rev.

    (2005)
  • D.A. Groneberg et al.

    Fundamentals of pulmonary drug delivery

    Respir. Med.

    (2003)
  • J.A. Hersey

    Ordered mixing: a new concept in powder mixing practice

    Powder Technol.

    (1975)
  • N. Islam et al.

    Surface roughness contribution to the adhesion force distribution of salmeterol xinafoate on lactose carriers by atomic force microscopy

    J. Pharm. Sci.

    (2005)
  • P.P.H. Le Brun et al.

    Dry powder inhalation of antibiotics in cystic fibrosis therapy: part 2: inhalation of a nevel colistin dry powder formulation: a feasibility study in healthy volunteers and patients

    Eur. J. Pharm.

    (2002)
  • W.I. Li et al.

    Aerosol particle transport and deaggregation phenomena in the mouth and throat

    Adv Drug Deliv. Rev.

    (1997)
  • C. LiCalsi et al.

    A powder formulation of measles vaccine for aerosol delivery

    Vaccine

    (2001)
  • E.A. Matida et al.

    A new add-on spacer design concept for dry-powder inhalers

    J. Aerosol Sci.

    (2004)
  • S.P. Newman et al.

    Evolution of dry powder inhaler design, formulation, and performance

    Respir. Med.

    (2002)
  • M.T. Newhouse et al.

    Clickhaler (a novel dry powder inhaler) provides similar bronchodilation to pressurized metered-dose inhaler, even at low flow rates

    Chest

    (1999)
  • H. Adi et al.

    Agglomerate strength and dispersion of salmeterol xinafoate from powder mixtures for inhalation

    Pharm. Res.

    (2006)
  • L. Agertoft et al.

    Lung deposition and systemic availability of fluticasone Diskus and budesonide Turbuhaler in children

    Am. J. Resp. Crit. Care Med.

    (2003)
  • R.E.C. Altounyan

    Inhibition of experimental asthma by a new compound-sodium cromoglycate

    Intal. Acta Allergol.

    (1967)
  • P.J. Atkins

    Dry powder inhalers: an overview

    Respir. Care

    (2005)
  • R. Backman et al.

    Fluticasone propionate via Diskus inhaler at half the microgram dose of budesonide via Turbuhaler inhaler

    Clin. Drug Invest.

    (2001)
  • A.K. Banga

    Delivery of protein therapeutics

    Business Brief.: Pharmatech.

    (2003)
  • J.V. Bennett et al.

    Aerosolized measles and measles–rubella vaccines induce better measles antibody booster responses than injected vaccines: randomized trials in Mexican schoolchildren

    Bull. World Health Organiz.

    (2002)
  • A.S.B. Beth et al.

    A piezo-electronic inhaler for local and systemic application

    Drug Deliv. Technol.

    (2004)
  • H. Bisgaard

    Drug delivery from inhaler devices. Lung deposition, clinical effect and cost effectiveness vary

    Br. Med. J.

    (1996)
  • H. Bisgaard

    Automatic actuation of a dry powder inhaler into a nonelectrostatic spacer

    Am. J. Respir. Crit. Care Med.

    (1998)
  • J. Blair et al.

    Modification of the pulmonary absorption of cyclosporine using Solidose technology

  • L. Borgstrom et al.

    Idealhalers or realhalers? A comparison of Diskus and Turbuhaler

    Int. J. Clin. Pract.

    (2005)
  • A.L. Bot et al.

    Novel lipid-based hollow porous microparticles as a platform for immunoglobulin delivery to the respiratory tract

    Pharm. Res.

    (2000)
  • G. Brambilla et al.

    Designing a novel dry powder inhaler: the NEXT TM DPI (Part 1)

  • B.A.S. Brown et al.

    A piezo-electric inhaler for local and systemic application

    Drug Deliv. Technol.

    (2004)
  • J. Bryan

    Novel inhaler devices: balancing innovation against price is important

    Pharm. J.

    (2005)
  • P.R. Byron et al.

    Drug delivery via the respiratory tract

    J. Aerosol Med.

    (1994)
  • P.R. Byron et al.

    Aerosol characteristics I: properties of the fine powders before and after aerosolizationby dry powder inhalers

    Pharm. Res.

    (1997)
  • Peter R. Byron

    Drug delivery devices: issues in drug development

    Proc. Am. Thoracic Soc.

    (2004)
  • P.A. Carter et al.

    Measurement of electrostatic charge decay in pharmaceutical powders and polymer materials used in dry powder inhaler devices

    Drug. Dev. Ind. Pharm.

    (1998)
  • CRER

    Guidance for Industry: Metered Dose Inhaler (MDI) and Dry Powder Inhaler (DPI) Drug Products

    (1998)
  • H.K. Chan

    Formulation challenges: protein powders for inhalation

    Drugs Pharm. Sci.

    (2003)
  • H.K. Chan

    Dry powder aerosol delivery systems: current and future research directions

    J. Aerosol Med.

    (2006)
  • H.K. Chan et al.

    Dry powder inhalers: challenges and goals for next generation therapies

    Pharm. Technol. Eur.

    (2007)
  • Chawla, B., Paul, S., 2008. Inhaler, PCT Int. Appl. WO 2008001132. Brintech International Limited,...
  • Cheatham, W.W., Leone-Bay, A., Grant, M., Fog, P.B., Diamond, D.C., 2006. Pulmonary delivery of inhibitors of...
  • A.R. Clark

    Medical aerosol inhalers: past, present and future

    Aerosol Sci. Technol.

    (1995)
  • Chen, Q., 2007a. Device for quantitatively dispensing dry powder and used with dry powder inhaler, CN 200710020974....
  • Chen, Q., 2007b. Device for rapidly evaluating dry powder from capsule in dry powder inhaler, CN 200710020975. Faming...
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