Chapter 6 - Drug Delivery Devices

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Following sections are included within this chapter. Please find the abstracts below.

6.1 Pressurized Metered Dose Inhalers by Stephen P. Newman, PhD

Pressurized metered dose inhalers (pMDIs) have been the most widely used devices for the maintenance therapy of asthma and chronic obstructive pulmonary disease (COPD) for several decades. The pMDI spray is self-powered by propellants held under pressure in the canister, and a metering valve ensures the delivery of a precise dose on each actuation. The pMDI has many practical advantages, being compact, convenient, portable and multi-dose, but it may give a highly variable lung dose when used by patients, many of whom cannot use the device correctly. Failure to actuate the pMDI while breathing in slowly and deeply has been identified as the most important error in pMDI technique. Training aids, breath-actuation mechanisms and improved instruction by health-care workers may address problems of poor inhaler technique. Improvements to both device and formulation enable many modern pMDIs to deliver warmer, more slowly moving and less forceful spray clouds than their historic counterparts. Dose counters are now commonly incorporated into pMDIs, and may be a regulatory requirement. Future improvements may make it possible to deliver markedly larger doses than have been possible previously, which would make pMDIs a suitable delivery platform for a wider range of drug molecules.

6.2 Spacers and Valved Holding Chambers by Sunalene Devadason, PhD

Spacers, primarily valved holding chambers (VHCs), are widely used to overcome some of the problems associated with the use of pressurized metered-dose inhalers (pMDIs). These include the difficulty experienced by patients in trying to coordinate the initiation of inhalation with the actuation of the pMDI. High oropharyngeal deposition of drug, which may result in both local and systemic side effects, is also a problem. Although the variability in output from pMDIs under optimized conditions in the laboratory is low, the variability when used in clinical practice is likely to increase considerably. Hence, the dose introduced into a holding chamber may vary significantly depending on the way in which the pMDI canister is handled before it is actuated. Several studies have shown that various design factors can influence the dose delivered from a holding chamber. These include spacer volume, shape, valve design, using multiple actuations, delay between actuation and inhalation, and construction material, which affects the level of electrostatic charge accumulating on the spacer surfaces. Several spacers which are made from low or anti-static materials are now available. Recommendations for optimal use of spacers, including inhalation techniques are outlined in this chapter, and vary according to patient age and inhalation coordination capability. Efficiency of drug delivery and lung deposition are also dependent on pMDI drug formulation and the patient’s anatomical and physiological characteristics.

6.3 Dry Powder Inhalers: An Overview by Anthony J. Hickey, PhD

Dry powder inhaler products have played an important role in the treatment and prevention of asthma and more recently chronic obstructive pulmonary disease. The considerations that go into formulation development to support these products cover a unique range of disciplines including analytical and physical chemistry, aerosol physics, device technology, process engineering and industrial design. An enormous research effort has been expended in the last half century to provide understanding of this complex dosage form. The guiding principles in considering the development of dry powder inhaler products encompass requirements for disease therapy, advantages and limitations of adopting certain technological approaches, and desirable features to facilitate patient use, which are all embodied in the target product profile.

6.4 Dry Powder Inhalers—From Bench to Bedside by Henry Chrystyn, BPharm, MSc, PhD, FRPHarmS, FHEA, Wahida Azouz, BSc, PhD, and Walid Tarsin, BSc, PhD

Dry powder inhalers (DPIs) are now widely prescribed and preferred by the majority of patients. These devices have many advantages over the traditional pressurized metered-dose inhaler (pMDI) but they do have disadvantages. The characteristics of the dose emitted from a DPI are affected by the inhalation maneuvre used by a patient. Each patient is different and the severity of their lung disease varies from mild to very severe. This affects how they use an inhaler and so determines the type of dose they inhale. An understanding of the pharmaceutical science related to DPIs is important to appreciate the relevance of how patients inhale through these devices. Also, each type of DPI has its unique dose preparation routine, and thus it is essential to follow these recommended steps because errors at this stage may result in no dose being inhaled. All issues related to the inhalation manoeuvre and dose preparation are addressed in this chapter. The importance of the inhalation technique is highlighted with a realization of inhale technique training and checking. During routine patient management, devices should not be switched nor doses increased unless the patient has demonstrated that they can and do use their DPI.

6.5 Nebulizers by James B. Fink, RRT, PhD and Kevin W. Stapleton, PhD

Nebulizers generate aerosols from liquid-based solutions and suspensions. Nebulizers are particularly well suited to delivering larger doses of medication than is practical with inhalers and are used with a broad range of liquid formulations. When the same drug is available in liquid or inhaler form, nebulizers are applicable for use with patients who will not or cannot reliably use a pressurized metered-dosed inhaler (pMDI) or dry powder inhaler (DPI) due to poor lung function, hand-breath coordination, cognitive abilities (e.g. infants, elderly) or device preference. In a nebulizer, liquid medication is placed in a reservoir and fed to an aerosol generator to produce the droplets. A series of tubes and channels direct the aerosol to the patient via an interface such as mouthpiece, mask, tent, nasal prongs or artificial airway. All nebulizers contain these basic parts, although the technology and design used can vary widely and can result in significant difference in ergonomics, directions for use, and performance. While many types of nebulizers have been described, the three categories of modern clinical nebulizers include: 1) pneumatic jet nebulizers (JN); 2) ultrasonic nebulizers (USN); and 3) vibrating mesh nebulizers (VMN). Nebulizers are also described in terms of their reservoir size. Small volume nebulizers (SVNs), most commonly used for medical aerosol therapy, can hold 5 to 20 ml of medication and may be jet, ultrasonic, or mesh nebulizers. Large volume nebulizers, typically jet or ultrasonic nebulizers, hold up to 200 ml and may be used for either bland aerosol therapy or continuous drug administration.

6.6 New Generation Nebulizers by Martin Knoch, Dr.-Ing.

Standard nebulizers are intended for general purpose use and typically are continuously operated jet or ultrasonic nebulizers. Evolutionary developments such as breath-enhanced and breath- triggered devices have improved delivery efficiency and ease of use, yet are still suitable for delivery of nebulized medications approved in this category.This section describes and compares different technologies as Smart Nebulizers using Adaptive Aerosol Delivery or controlled breathing systems, Vibrating Mesh Nebulizers and Soft Mist Inhalers.

However, recent developments of vibrating membrane or mesh nebulizers have given rise to a significant increase in delivery efficiency requiring reformulation of former drug products or development of new formulations to match the enhanced delivery characteristics of these new devices. In addition, the electronic nature of the new devices enables tailoring to specific applications and patient groups, such as guiding or facilitating optimal breathing and improving adherence to the therapeutic regimen. Addressing these patient needs leads to new nebulization technologies being embedded in devices with fundamentally distinct functionality, modes of operation and patient interfaces. Therefore, new generation nebulizers can no longer be regarded as one category with fairly similar performance characteristics but must be clinically tested and approved as drug/device combinations together with the specific drug formulation, similar to the approval of pressurized metered-dose inhalers (pMDIs) and dry powder inhalers (DPIs). From a regulatory viewpoint, it is required that drug and device are associated with each other as combinations by clear, mutually conforming labels or, even more desirably, by distinct container-closure systems (closed system nebulizer).