In the field of pulmonary drug delivery, extensive R&D efforts have been expended on the better ability of the drug to reach the target site in the lungs for maximum therapeutic benefit. Dry powder inhaler (DPI) technology has remained a key focus to achieve this objective in the treatment of chronic obstructive pulmonary diseases (COPD) and asthma.

Basic features of DPIs

DPI technology either uses a drug alone or drug particles mixed with carrier particles such as lactose. Drug particles should be in the range of 1 to 5 microns to ensure that it reaches lung tissues and small airways. The shape of drug particles is also important since elongated particles have better penetrability. Capsule-based DPI formulations use hydroxypropylmethylcellulose (HPMC) or hard gelatin capsules. Capsule properties influence the performance of DPI formulation dramatically. The capsule is activated to release the formulation by cutting, piercing, or shear-force opening. There are approximately 1 to 8 needles used for puncturing the capsules either from the sides or from the top. HPMC capsules have been shown to exhibit better puncturing than hard gelatin capsules. The moisture content of the capsule should be kept in equilibrium with the capsule content. The amount of drug powder that can be retained in the capsule depends on the surface properties of the capsule and interactive forces between mixtures. Breezhaler® is an example of a recent capsule-based DPI used to deliver β-adrenergic bronchodilatorꟷIndacaterol Maleate and the long-acting muscarinic antagonistꟷGlycopyrronium.

Extending applications of DPI to the other therapeutics

In the past few decades, the use of single-use, disposable capsule-based DPI has increased due to the growth of generic devices for the administration of drugs in COPD, asthma, infection, lung cancer, and tuberculosis. Disposable DPIs are not only cheaper and simple to use but also are reproducible and highly effective. One such example is PulmoSphere™ containing antibiotic tobramycin. Similarly, ELLIPTA® DPI was developed for the delivery of once-daily therapies for the treatment of asthma and COPD. Vancomycin, Clarithromycin, Tobramycin, and Azithromycin have been delivered by DPI for respiratory infections. DPI of Diatrizoic acid was also developed as a radiocontrast agent for imaging of the airway. DPI of liposomal Rifampicin was developed to treat pulmonary tuberculosis. Cyclosporin A was delivered as a DPI for immunosuppressant activity in cases of lung transplant rejection.

DPIs have a long way to go

Although existing DPIs are efficient in delivering drugs, there are several areas that need close attention for improvement. For example, capsule-based DPI need individual loading of drug units which may be inconvenient for some patients. Also, proper loading of the device requires certain steps that may be difficult for children. Currently used DPI systems exclusively depend on the inspiratory force by the patient to disperse the drug powder. This means the deposition of drug particles depends on the inspiratory capacity of the patient. This intra- and inter-patient variability of dosage delivered to the lungs is a major concern as it can lead to the under-dosing of the drug and reduced pharmacological activity. It is, therefore, expected that future development in capsule-based DPI will focus on the simplicity of use, suitability, and consistency in release.

References:

1. Lavorini, F., Pistolesi, M., & Usmani, O. S. (2017). Recent advances in capsule-based dry powder inhaler technology. Multidisciplinary respiratory medicine, 12(1), 11.

2. Pavkov, R., Mueller, S., Fiebich, K., Singh, D., Stowasser, F., Pignatelli, G., … & Rietveld, I. (2010). Characteristics of a capsule-based dry powder inhaler for the delivery of indacaterol. Current medical research and opinion, 26(11), 2527-2533.

3. de Boer, A. H., Hagedoorn, P., Hoppentocht, M., Buttini, F., Grasmeijer, F., & Frijlink, H. W. (2017). Dry powder inhalation: past, present and future. Expert opinion on drug delivery, 14(4), 499-511

4. Muralidharan, P., Malapit, M., Mallory, E., Hayes Jr, D., & Mansour, H. M. (2015). Inhalable nanoparticulate powders for respiratory delivery. Nanomedicine: Nanotechnology, Biology and Medicine, 11(5), 1189-1199.