Review of dry powder inhalers

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Abstract

The search for alternatives to metered-dose inhalers has accelerated recently in a bid to find effective products that do not use chlorofluorocarbon (CFC) propellants. This paper reviews the factors to be considered in developing dry powder inhalers (DPIs), particularly the formulation, metering design and flow path in the device. The advantages and disadvantages of current DPIs are discussed and possible future approaches outlined.

Introduction

Inhalation drug delivery has been used for many years for the delivery of pharmacologically active agents to treat respiratory disease. Traditional asthma therapy with bronchodilators, steroids, mast cell stabilizers, and anticholinergic drugs has primarily used the pressurized metered-dose inhaler (MDI). However, this delivery system is now under increasing threat because of the environmental concerns regarding chlorofluorocarbon (CFC) propellants. A range of alternative devices, such as dry powder inhalers, which do not contain propellants are being evaluated and developed. This article covers the development of dry powder inhalers, including the design of the formulation, metering system and flow path. The advantages and disadvantages of some design options (summarised in Fig. 1) are discussed.

Powder inhalers are versatile delivery systems which may require some degree of dexterity to operate, although one of the objectives of recent developments has been to simplify their operation. Typically, they dispense a metered quantity of powder in a stream of air drawn through the device by the patients own inspiration. In the design of a new powder inhaler consideration must be given to optimising the formulation of the powder containing the drug substance to ensure a chemically stable and consistent dose; design of the metering system within the inhaler to provide consistent doses over a range of inhalation conditions; and design of the powder inhaler itself to produce a convenient device that is comfortable and easy for the patient to use.

Inasmuch as these devices do not require CFC propellants to disperse the drug, they can be regarded as ozone-friendly delivery systems. However, concerns that they will not be able to totally replace MDIs due to limitations of dose delivered and flow rates achieved through the devices for severely diseased patients are probably valid [1], based on the capabilities of currently available powder inhalers. Vidgren et al. [2]have shown different deposition patterns in healthy volunteers from the same formulation in four single-dose DPIs. Newman et al. [3]have also shown different in-vivo deposition patterns in healthy volunteers using Turbuhaler inhalers operated at optimal and sub-optimal peak inspiratory flow rates. Clearly, some current designs of DPIs are subject to variations in performance due to differences in inhalation flow rates. Future designs may require that the dispersion of the powder dose be independent of patient inhalation.

Section snippets

Formulation design

Of critical importance in the development of powder inhalation products is the optimization and control of flow and dispersion (deaggregation) characteristics of the formulation (see K. Johnson, Wen-I. Li and David Edwards, this issue). These properties are a function of the principal adhesive forces between particles, including Van der Waals forces, electrostatic forces and the surface tension of absorbed liquid layers [5]. The forces are influenced by several fundamental physicochemical

Metering design

Whether a drug only or a drug–carrier system is adopted, a key decision in the design of a DPI is whether to use a factory metered dose or to include a reservoir and metering mechanism in the device itself.

Early popular DPIs utilised factory-metered doses. Conventional capsule-filling technology, already well established in the early 1970s, was used to manufacture unit doses that could be inhaled from relatively simple devices.

The concept of the Spinhaler was first described in the early 1970s

Manufacturing design

When the DPI design moves away from the more simple gelatin capsule technology of inhalers such as the Spinhaler, considerations have to be given to the complex design of the device itself and to the development of the specialist equipment necessary to manufacture the device components and to fill and assemble the final product. For example, Brindley et al. [20]describe the complex procedure involved in producing a multi-dose foil blister strip and packaging it in the Diskus device, together

Flow path design

In combination with the design of the formulation and the approach to metering, the third critical factor that determines product performance is the flow path of the device, particularly between the exposed dose to be inhaled and the exit of the mouthpiece. An ideal flow path design would allow efficient and consistent emptying of the device across a wide range of flow rates, with sufficient turbulence to disperse/deaggregate the powder and thereby provide an effective `lung dose'.

The flow path

Functional design

Although separate from product performance, the patient-related features of the device are also an integral part of the design. Ease of use is the most fundamental aspect, particularly for old or very young patients where manual dexterity may be limited. Increasingly, however, additional features will be expected in modern devices, such as an accurate dose counter, integral cover (if necessary to protect the mouthpiece), a locking mechanism to indicate that the labelled number of doses have

Novel inhalation delivery systems

Interest in the design of more compact portable inhalation delivery systems is increasing. The patent literature offers numerous examples of applications for novel delivery systems that purport to be potential replacements for the pressurized MDIs, and much is being published in this field 32, 33. Consideration is being given to delivery of biotherapeutic materials, such as some proteins and peptides, by inhalation aerosol [34].

A number of potential new devices are emerging in the powder area,

Summary

Common to all inhalation dosage forms and delivery systems is the need to generate the optimum `respirable dose' (particles with aerodynamic diameters <5.0 μm) of a therapeutic agent consistently and reliably. This is a key performance feature in the rational design and selection of a delivery system. Moreover, this performance, in terms of aerosol quality, should be demonstrated throughout the product's shelf life, in addition to the more usual chemical and physical stability criteria. When

References (35)

  • Dolovich, M.B. and Ramsdale, E.H. (1990) Can. Med. Assoc. J., 142,...
  • Vidgren, M., Karkkainen A., Karjalainen, P., Paronen, P. and Nuutinen, J. (1988) Effect of powder inhaler design on...
  • Newman, S.P., Moren, F., Trofast, E., Woodman, G. and Clarke S.W. (1987) Deposition patterns in man from Turbuhaler: a...
  • Hinds, W.C. (1982) Adhesion of particles. In: W.C. Hinds (Ed.), Aerosol Technology: Properties, Behaviour and...
  • Hickey, A.J., Gonda, I., Irwin, W.J. and Fildes, F.J.T. (1990) Factors influencing the dispersion of dry powders as...
  • Chawla, A., Taylor, K.M.G., Newton, J.M. and Johnson, M.C.R. (1994) Production of spray-dried salbutamol sulfate for...
  • Bell, J.H., Hartley, P.S. and Cox, J.S.G. (1971) Dry powder aerosols I. A new powder inhalation device. J. Pharm. Sci....
  • Auty, R.M., Brown, K., Neale, M.G. and Snashall, P.D. (1987) Respiratory tract deposition of sodium cromoglycate is...
  • Chan, H.-K. and Gonda, I. (1989) J. Pharm. Sci. 78,...
  • Vidgren, M., Vidgren, P., Uotila, J. and Paronen, P. (1988) Acta Pharm. Fennica 97,...
  • York, P. and Hanna, M. (1996) Particle engineering by supercritical fluid technologies for powder inhalation drug...
  • Ganderton, D. (1992) The generation of respirable clouds from coarse powder aggregates. J. Biopharm. Sci. 3,...
  • Kjellman, N.-I.M. and Wirenstrand, B. (1981) Allergy 36,...
  • Pedersen, S. and Steffensen, G. (1986) Fenoterol powder inhaler technique in children: Influence of inspiratory flow...
  • Wetterlin, K. (1988) Turbuhaler: A new powder inhaler for administration of drugs to the airways. Pharm. Res. 5,...
  • Sumby, B.S., Churcher, K.M., Smith, I.J., Grant, A.C., Truman, K.G., Marriott, R.J. and Booth, S.J. (1993) Dose...
  • Gunawardena, K.A., Pleace, K.J. and Clay, M.M. (1994) Salmeterol delivered from a new multi-dose powder inhaler...
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