Powder unit-dose systems

The active inhaler made by Nektar Therapeutics (formerly Inhale Therapeutic Systems, United States), called Pulmonary Delivery System (PDS), mechanically compresses a fixed volume of air required for delivery and dispersion of a premetered dry-powder unit dose by a spring-loaded pump (Fig. 8.10). Generation of the respirable aerosol cloud thus is independent of the inspiration effort exerted by the patient. The aerosol is generated in a transparent holding chamber that acts as a spacer from which the patient inhales the standing cloud of particles (Patton 1997). The PDS device is actually close to market for inhaled delivery of insulin under the trade name Exubera. 

Early dry powder inhaler devices were all unit-dose systems and depended on loading and triggering procedures. The Spinhaler and Rotahaler are two early examples of DPI technology. Both utilize premetered doses packed into hard gelatin capsules although different mechanisms of powder delivery are employed ... 

A multiparticulate drug delivery technology for producing CR and taste masked preparations such as liquids, suspensions, effervescent and chewable tablets, reconstitutable powders, and unit dose sachet or sprinkle systems. 

Current challenges facing the development of these systems for macromolecules include moisture control, efficient powder manufacturing, reproducible powder filling, unit dose packaging and development of efficient reliable aerosol dispersion and delivery devices. 

By 2004, the ADD market was segmented in three forms powder, gel, and unit dose. Approximate market share for these forms in the U.S. was 40, 40, and 20% respectively. While liquid gel systems continued to grow, they were challenged by the unit dose segment that consisted of solid, liquid, or hybrid products. 

Although enzyme-based systems comprise the bulk of the powder market, it has only been in recent years that they have emerged in automatic dishwasher gels. Currently enzyme-based liquid products comprise about 10% of the ADD market. This comprises both bottled gels and unit dose sachets. Unlike the powder formulas, liquid enzyme formulas with bleach have not been successfully delivered. Efforts in this area include the development of a gel containing encapsulated bleach [187-189], New enzymes are continuously being developed that are more bleach stable. As these become commercially viable, new aqueous gel products that provide the benefits of both bleach and enzyme cleaning will be available to the consumer. 

An additional general method to reduce bypass is through vacuum deaeration. Miller9 performed experiments on a low-density active blend with and without vacuum deaeration, while holding all other parameters constant, and quantified the bypass for each trial. With the vacuum deaeration engaged, the bypass rate was 2% as compared to the control rate of over 20%. He also observed that the powder feed was uneven and the compact quality was not uniform. Most units are equipped with this capability and it should be considered to minimize bypass for low-dose products. However, vacuum deaeration can cause potency loss, unless the collected material is recirculated to the feed system. 

Powdered activated carbons offer the advantage of low cost compared to granules in terms of both purchase price and capital expenditure (investment in adsorber units, pumps, etc). The cost of PAC is about 1.00/kg versus 2/kg for GAC [19]. For a system treating 4 million/day the cost is about 0.03/1,000 L [67], A wider range of impurity removal levels can be attained with powdered carbon, where the dose of carbon per batch can be adjusted, depending on the type and concentration of the contaminants [68]. GAC is normally used in continuous flow deep beds and is advantageous when variations in adsorption condi-... 

The development of multidose DPIs was pioneered by A. B. Draco (now a division of AstraZeneca) with their Turbuhaler [53]. This device is truly a metered-dose powder delivery system. The drug is contained within a storage reservoir and can be dispensed into the dosing chamber by a simple back-and-forth twisting action on the base of the unit (Fig. 7). The device is capable of working at moderate flowrates and also delivers carrier-free particles [54]. However, one of the drawbacks of the Turbuhaler has been the fact that it has... 

Unlike most other drug delivery systems, those in the respiratory area can have a major influence on physician/patient acceptance. A wide range of devices are available in the three main categories of dry powder inhalers (DPIs) and metered dose inhalers (MDIs), i.e., pressurised aerosols and nebulisers. The preferred type of inhaler varies considerably between countries (e.g., DPIs in Scandinavia and MDIs in the United States), and between patient groups (e.g., nebulisers for paediatrics). 

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