Nektar

Pre-approval safety and efficacy clinical studies involved product administration to 2500 adults with either type-1 or -2 diabetes. The primary efficacy parameter measured was glycaemic control (as measured by the reduction from baseline in haemoglobin Ale). Hypoglycaemia was the most commonly reported adverse effect. Trials also showed a greater decline in pulmonary function in the Exubera group, and product should not be administered to patients with underlying lung disease, or to smokers. Exubera was developed by Nektar Inc. and is marketed under licence by Pfizer. 

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. 

Figure 8.10 PDS device developed by Nektar Therapeutics for pulmonary delivery of insulin.

The MicroDose DPI (MicroDose Technologies, United States) is a breath-activated device that includes a piezoelectric vibrator that converts electrical energy from a battery to mechanical motion that is then transferred into the dry powder. The vibration energy deaggregates and aerosolizes the dose. By controlling the energy input, i.e., the amplitude and frequency of the vibration, the DPI is claimed to be usable for various compounds. As with the devices from Nektar and Dura, the MicroDose DPI uses accurately filled unit-dose blisters. 

Figure 8.13 Scanning electron micrograph of spray-dried PulmoSol particles (left) and PulmoSpheres particles (right), both developed by Nektar Therapeutics. [From Peart and Clarke (2001). Reproduced with permission from Russell Publishing.]...

Activated PEGs are available commercially from many sources, in particular Nektar Therapeutics, which now supplies the starting material for most such drug products that are FDA approved or in advanced clinical development. 

Insulin inhalation - Pfizer/NektarTherapeutics HMR 4006, inhaled PEG-insulin - Nektar, PEGylated insulin - Nektar, Drugs R D 2004. 5 166-170. 

Stevenson, C. Hastedt, J.E. Lehrman, S.R. Chiang, H.S. Bennett, D.B. Lesikar, D. Yang, B. Gong, D. Cabot, K. Inhaleable spray dried 4-helix bundle protein powders having minimized aggregation. US patent 6,569,406, Aug 7, 2001, Nektar Therapeutics San Carlos, CA. 

Herm E. Snyder Nektar Therapeutics, San Carlos, California, U.S.A. 

FIGURE 2 Clinical spray drying facility. Source Courtesy of Nektar Therapeutics. 

FIGURE 18 Spray dried panicles using NEKTAR Technology (www.nektar.com). 

The authors would like to thank the following people at Nektar Therapeutics whose work contributed to this chapter Andrew Boeckl. Dr. Christopher Varga, and Dr. Zhuoxiong Mao. 

Bennett DB, K. BT, Snyder HE, Platz RM, Inventors Nektar Therapeutics, Inc., assignee. Spray drying process control of drying kinetics. US patent 20030044460, 2000. 

Methoxy poly(ethylene) glycol butyraldehyde (MW 2,000), mPEG-SH (MW 2,000) (all from Nektar Therapeutics, Huntsville, AL). 

Maleimide-PEGjggg-DSPE (Shearwater Polymers, Huntsville, AL, USA, currently Nektar Pharmaceuticals). This lipid can be stored as powder or as stock solution in ethanol at -20°C. 

Much interest has been focused recently on developing delivery systems that deaggregate the powder [63], for this effectively minimizes formulation development work. Some of these systems are extremely complex in operation and may prove difficult to achieve in everyday operations. In addition, some designs that have already been achieved (e.g., Nektar Therapeutics Enhance ... 

A variety of mechanisms for assisting with the dispersion of the powder have been adopted, including impellors (Spiros), compressed air assist (Nektar), vibration (Oriel, Microdose), and impact hammers (3M, DelSys). 

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