Issue link: https://www.e-digitaleditions.com/i/1481142
26 OctOber 2022 Inhalation ing under the tight controls that today's regulations impose. e ever-larger, multi-disciplinary develop- ment team has since, however, become essential. Spe- cialist development companies have emerged with bright ideas, with dozens of patents filed describing formulation technology and devices, but the gener- ally slow pace of pharmaceutical development and the uncertainties of new product development has not infrequently led to funding issues or companies being subsumed into larger pharma. Table 1 lists some of the types of devices (capsule, reservoir, blis- ter) that reached the market. Many others did not. All DPIs have several common features: a formula- tion, a dose storage system, moisture protection, an air inlet system, and a powder lift and de- aggregation system. Additionally, there are considerations that may apply to particular devices; for example, in- device dose metering, breath actuation, counters and lock-outs, and filling technologies. ere are patient, social and environmental considerations as well. No DPI is capable of delivering its full dose to the lung; some is retained within the plastic elements of the device, some remains attached to the carrier, some is deposited in the mouth and there are other losses. Formulation One of the major challenges that faces successful inhalation of dry powder is that, typically, the active pharmaceutical substance is a microgram quantity of material with poor flow properties. In many cases, the quantity is less than the amount that can be con- sistently metered by industrial filling processes. To cope with this situation, a "carrier" substance is used to dilute and loosely bind with the powdered active. Lactose has emerged as the most commonly- The last 70 years In the 1950s, the pressurized metered dose inhaler (pMDI) was introduced and seemed to revolution- ize portability and delivery but two inherent limita- tions existed: the metered dose inhaler capacity was relatively small and patients struggled to coordinate the action of inhalation and actuation of the device. e next landmark dry powder development that addressed both these limitations was the Spinhaler ® (Fisons Limited), a capsule-based device delivering a 20 mg payload of sodium cromoglycate (Figure 4). 10 e pace of dry powder inhaler (DPI) development from this point onward has been astounding. Early, highly-driven pharmaceutical developers, such as Roger Altounyan at Fisons and Kjell Wetterlin at Astra, were able to develop products without work- Table 1 Various dry powder inhalation devices that reached the market Device Type Company Novel Feature Spinhaler ® Capsule Fisons First modern DPI Rotahaler ® Capsule Allen & Hanbury (GSK) Delivering separately corticosteroid and short-acting bronchodilator Turbuhaler ® Reservoir Astra Multidose, spheronized pure drug formulation, "fuel gauge" counter, Mk III for combinations Diskhaler ® Blister Allen & Hanbury (GSK) Multidose, foil blister disks (pierced) Diskus ® Blister GSK Multidose, blister strips (peeled) combination formulations Novolizer ® Reservoir Asta (AstraZeneca) Multidose, replaceable reservoir, dose feedback indicator, breath-actuated membrane Ellipta ® Multiple Blister GSK (Glaxo Group) Multiple blister, two separate combination components, subsequently triple therapy Exubera™ Blister Pfizer Single insulin blister, discharged into spacer Figure 4 Spinhaler ® dry powder inhaler (Fisons)