Advancements in Dry Powder Inhaler

Abstract

The dry powder inhaler (DPI) has become widely known as a very attractive platform for drug delivery. DPIs are being used for the treatment of asthma and chronic obstructive pulmonary disease by many patients. There are over 20 devices presently in the DPI market. DPIs are preferred over nebulizers and pressurized metered dose inhalers. However, some of the challenges of DPI are dependence on inspiratory flow (unsuitable for young children, elderly people), systemic absorption due to deposition of drug in deep lung (unsuitable for local diseases treatment), and increase in upper airway deposition of a large fraction of coarse particles. Hence, there is a need to address these unmet issues. The interpatient variation can be minimized by developing devices independent of patient's inspiratory flow rate or active based powder mechanism. This article reviews DPI devices currently available, advantages of newly developed devices, and formulation technologies. The platform technologies are developed to improve aerosolization and dispersion from the device and decrease the patient related factors. The DPI delivery system has been expanded to treatment of non-respiratory diseases such as migraine and diabetes. The development of innovative DPI device and formulation technologies for delivering therapeutic proteins such as insulin has been accelerated to overcome the problems associated with conventional insulin therapy.

The future of dry powder inhaled therapy: Promising or discouraging for systemic disorders?

“…Despite the product showing satisfactory aerosolization performances, efficacy and safety, and having passed phase III clinical trials, Eli Lilly still decided to terminate its development after considering that the commercial potential of AIR® insulin was not strong given the safety deficiencies and financial loss of Exubera® demonstrated ( Ledet et al, Jul. 2015 , Srinivasan and Shetty, Feb. 2017 , “Eli Lilly drops inhaled insulin program,” Reuters, Mar. 07, 2008 ).…”

“…The drug formulation comprises of Technosphere® insulin inhalation powders, a dry powder mixture of recombinant human insulin-Technosphere® microparticles, with a median diameter of 2.0 to 3.0 μm ( Heinemann and Parkin, 2018 ). The Technosphere® is composed of fumaryl diketopiperazine (FDKP), which is highly soluble at pH>6 but can self-assemble into microspheres through the process of hydrogen binding in an acid environment ( Srinivasan and Shetty, Feb. 2017 , Easa et al, Feb. 2019 , Lee et al, Nov. 2018 , Rahimpour et al, May 2014 ). During the assembly process, insulin in the solution is captured and entrapped when the FDKP precipitates and agglomerates, causing the formation of low-density particles ( Berkenfeld et al, Jun.…”

“…The delivery of drugs directly to the lung, is typically achieved by an aerosol (a suspension of small liquid droplet or fine solid particle dispersed in gas medium), in the form of a spray ( Tellier et al, Dec. 2019 ). Nebulizer, pressurized metered-dose inhaler (pMDI), and DPI are the three primary technologies used to form sprays for pulmonary drug delivery ( Srinivasan and Shetty, Feb. 2017 ). First introduced during the 19 th century, the nebulizer is a device that delivers the liquid medication to lungs in the form of mist.…”

“…As an alternative, DPI delivers medication to the lungs in the form of fine powder. Although it emerged as a latecomer in 1967, DPI has received more attention and preference nowadays for several reasons ( Lin et al, Sep. 2015 ): The solid state of DPI formulation is more stable than the liquid form of the nebulizer and pMDI ( Srinivasan and Shetty, Feb. 2017 , Shur et al, Sep. 2015 ). The elimination of propellants, chlorofluorocarbon (CFCs) or hydrofluoroalkanes (HFAs), avoids ozone depletion and greenhouse issues ( Devrim et al, Nov. 2011 ).…”

Recent Advances and Future Prospects of Non-Invasive Insulin Delivery Systems

“…, thin epithelial layer and the short distance between epithelium and alveolar blood vessels that is beneficial for effective drug absorption [35,36]. Thus, delivery of insulin through lungs was the first method reported as an alternative to SC injections [4,37].…”