Dry powder inhalers (DPIs) have reshaped the treatment of pulmonary disorders and the device has played a key role in the success. Not only do they retain all the benefits of pressurised metered–dose technology but most importantly, they ensure effective, affordable, and sustainable drug delivery.    

Although a large number of DPIs are using capsules as a vehicle for dose administration, pharma companies are developing other options for dosing the drugs and one of them is blisters. A typical blister pack consists of a base material, with one or more cavities into which the drug is placed, and a lidding film that seals the base enclosing the cavity. Blister packs are quite common in the pharma industry and have been used for packaging unit doses of powders, tablets, and capsules.  

Considerations for blister-based DPIs 

Blister-based DPIs are preferred for highly moisture-sensitive products. The device contains a ring of aluminium blisters inside, each blister containing a single, predetermined dose of drug powder. The number of doses administered is indicated by the dose counter incorporated in the device. Actuation of the inhaler causes piercing of the blister and the airflow generated upon inhalation leads to the release of powder from the blister. 

While designing a blister-based DPI formulation, it is important to ensure that the blister material used for the DPIS protects the drug dose from physical and chemical changes. But at the same time, the blister must have an appropriate rigidity and mechanical properties to enable easy piercing and dose release. Blister packs composed of polypropylene, polyvinyl chloride, polystyrene, and aluminium are commonly used in DPIs. 

Marketed products 

Following are a few examples of marketed or patented products available as blister-based DPIs. 

1. Microdose® DPI is used to deliver Atropine as a systemic and pulmonary treatment for the extended recovery period after chemical weapons exposure. The device uses a piezoelectric vibrator for converting electric energy to mechanical motion. The small needles pierce the blister before the patient breaths. The inhaler sensor upon detecting the threshold level of the patient’s inspiratory flow activates the piezoelectric vibrator which further deaggregates the drug powder released from the blister. Microdose® DPI is reusable for up to 6 months or longer.   

1. Acu–Breathe™ DPI utilises a trigger point mechanism, wherein the drug is released from blisters only after a desired inspiratory flow-rate is achieved. Foil blisters with a dose capacity of 25 mg are pierced using dual piercing technology. Acu-Breathe™ is used to deliver Fluticasone propionate for treating asthma.   

1. Diskus™ is a simplified inhaler designed to provide one–month medication without the need of manually replacing the spent blisters or cartridges. It houses a coiled blister strip of 60 double foil-wrapped individual doses of Salmeterol and Fluticasone powder combination. A sliding lever and ratchet are used to position the blister properly which is then followed by simultaneous peeling of two layers of foil apart and exposing the dose ready for inhalation. Diskus™ has been used for the treatment of asthma and COPD. 

1. Diskhaler® is used to deliver Zanamivir in the treatment of influenza. The DPI is used in conjunction with Rotadisk™ which contains 4 to 8 regularly spaced double-foil blisters containing the drug and lactose excipient. The use of lactose ensures dose uniformity as it increases the mass of powder for each dose and improves the dose metering accuracy. Also, it reduces the effect of inhalation flow-dependant dose emission. Rotadisk™ blisters are loaded on Diskhaler® and individual blister gets pierced when the patient lifts the mouthpiece lid of Diskhaler®. The dose is released as the patient inhales through the device.  

1. Ellipta® is a single- or two-strip inhaler pre-loaded with 1 month’s supply of pre-filled, foil-laminated, individually sealed blisters containing drugs. Monotherapy uses a single strip whereas, for combination therapy, the two-strip configuration is used. In this, one dose from each blister strip is delivered simultaneously during a single inhalation. The two-strip configuration gives flexibility to the formulation scientists to develop each product individually as they are stored separately in the device and combined only at the point of inhalation. Ellipta® is available to deliver three different drugs (Fluticasone furoate, Umeclidinium, Vilanterol trifenatate) for asthma and COPD. 

1. Puffhaler® is an example of an inline DPI that is actuated by an external air source instead of the patient’s inspiratory flow and hence, has a special benefit of being used for delivering drugs to infants, children, and patients with compromised lung function or who need ventilator support. Puffhaler® has been developed to deliver the measles vaccine as a dry powder to children and infants in developing countries. It consists of a squeeze bulb, burst valve, blister powder storage, and reservoir mask. When the squeeze bulb is compressed, it causes the silicone burst-valve pop open, dispersing the powder out of a blister into a reservoir. The 200 cc reservoir is detached and affixed to a facemask from which the patient breathes for 30 s to become vaccinated (Puff-mask).      

Takeaway  

When it comes to delivering large dose drugs through pulmonary routes, blister-based DPIs definitely rank higher in the list. The other benefits such as high accuracy dosing, minimal handling, a high number of pre-loaded doses, and suitability for moisture-sensitive drugs further make them an effective and user-friendly inhalation dosage form. Future research in this area may focus on the development of cost-effective, less bulky devices, and biodegradable blister packs. 

References 

1. Donovan MJ, Gibbons A, Herpin MJ, Marek S, McGill SL, Smyth HD. Novel dry powder inhaler particle-dispersion systems. Therapeutic delivery. 2011 Oct;2(10):1295-311. 

1. Ninane V, Vandevoorde J, Cataldo D, Derom E, Liistro G, Munghen E, Peché R, Schlesser M, Verleden G, Vincken W. New developments in inhaler devices within pharmaceutical companies: a systematic review of the impact on clinical outcomes and patient preferences. Respiratory medicine. 2015 Nov 1;109(11):1430-8. 

1. Grant AC, Walker R, Hamilton M, Garrill K. The ELLIPTA® dry powder inhaler: design, functionality, in vitro dosing performance and critical task compliance by patients and caregivers. Journal of aerosol medicine and pulmonary drug delivery. 2015 Dec 1;28(6):474-85. 

1. Chrystyn H. The DiskusTM: a review of its position among dry powder inhaler devices. International journal of clinical practice. 2007 Jun;61(6):1022-36. 

1. Laube BL. The expanding role of aerosols in systemic drug delivery, gene therapy, and vaccination. Respiratory care. 2005 Sep 1;50(9):1161-76. 

1. Krueger M, Metzger B, Trunk M, Schiewe J, inventors; Boehringer Ingelheim International GmbH, assignee. Blister for inhalers. United States patent application US 12/949,401. 2011 Mar 17.