Spray-Freeze-Drying

Until atmospheric spray-freeze-drying equipment becomes commercially available, the development of formulation will be mainly based on the Trial and Error approach, and the validation of the classical lyophilization procedure will remain difLcult. 

FIGURE 20.8 A particle of dextran as a product of an atmospheric spray-freeze drying process. (From Leuenberger, HJ. Nanoparticle Res., 4, 111-119 (2002c).)... 

Leuenberger, H., Spray freeze drying-the process of choice for low water soluble ddu teho particle Res.,... 

Spray freeze drying also has been proposed as an alternative technology to produce light and porous particles for peptide and protein delivery. Liquid nitrogen is used as recipient agent, into which the formulation is sprayed. The formed microparticles are harvested and lyophilized eventually. DNase and monoclonal anti-IgE antibodies have been used to demonstrate the feasibility of this concept (Maa et al. 1999). Promaxx microspheres are manufactured in a phase-separation process between water-soluble polymers and therapeutically active protein that results in particles having a high protein payload of up to 90 percent (Brown et al. 1999). 

Maa, Y., Nguyen, P., Sweeney, T., et al. Protein inhalation powders Spray drying vs. spray freeze drying. Pharm. Res. 16(2) 249-254, 1999. 

Maa et al. [3.84] used spray drying and spray freeze-drying (see Chapter 5, [5.13, 5.14]) to produce protein powders for inhalation from deoxyribonuclease (rhDNase) and anti-IgE monoclonal antibody (anti-IgE Mab) with lactose as carrier. Spray freezedrying produced light and porous protein particles with superior aerosol performance. 

Fig. 5.3 Schematic diagram of the ultrasonic spraying freeze-drying apparatus.

Itatani, K., Akiyama, K., Aizawa, M., Scott Howell, F., Okada, I. Sinterability of apatite-zirconia composite powder prepared by ultrasonic spray freeze-drying technique. J. Soc. Inorg. Mater. Jpn. 286,194-202, 2000... 

Carrasquillo, K. G., Stanley, A. M., Aponte-Carro, J. C., DeJesus, P, Costantino, H. R., Bosques, C. J., and Griebenow, K. (2001), Non-aqueous encapsulation of excipient stabilized spray freeze dried BSA into poly(lactide-co-glycolide) microspheres results in release of native protein,/. Controlled Release,76,199-208. 

Other methodologies may be employed for specific drug products. For microencapsulated, spray-dried, and spray-freeze-dried formulations, an assessment of the particle size may be critical. Lyophilized, spray-dried, and spray-freeze-dried formulations must be... 

Constantine HR, et al. Protein spray-freeze drying. Effect of atomization conditions on particle size and stability. Pharm Res 17(11) 1374—1383, 2000. 

A more recent approach is the formation of a solid-in-oil-in-water emulsion (s/o/w) before solvent evaporation [18]. This involves the formation of solid protein particles by either spray drying or spray freeze-drying, followed by the dispersion of... 

Keywords Pulmonary Protein Spray-drying Spray freeze-drying Supercritical fluids Aerodynamic... 

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