Porous freeze-drying

The collapse temperature is identified as the temperature at which this structure is observed to distort or to flow (formation of white zones on the microscopic images). Above the collapse temperature, the mechanical structure of the porous freeze-dried cake is destroyed. This identification is only an estimation since the collapse phenomenon (unlike melting) does not occur at a sharply defined temperature. 

Cationic HGs swell and release a drug in the low pH environment of the stomach (Fig. 3.6). Risbud et al. (2000) prepared a pH-sensitive, chitosan/ poly(vinyl pyrrolidone) (CS/PVP)-based, controlled drug release HG using air-dried and freeze-dried amoxiciUm. Porous freeze-dried hydrogel exhibited superior pH-dependent swelling properties over non-porous air-dried HGs. Freeze-dried membranes released around 73% of the amoxicillin (33% by air-dried) in 3 h at pH 1.0, and thus had the better drug release properties. 

Steinbach, G. Equations for the heat and mass transfer in freeze-drying of porous and non porous layers and bodiesm, p. 674 bis 683. International Institute of Refrigeration <1IR> (XIII, Washington 1971)... 

Fig. 2.17. Coils in a condenser covered by ice, observed through a window during two freeze drying processes. Left Smooth, solid surface. Right Porous, snow-like surface, which occurs typically, if the pressure of permanent gases during MD is high (photographs Dr. Otto Suwalck, D-48727 Billerbeck).

Fig. 3.25.1. Porous structure of collagen sponge produced by freezing in a cryogenic bath at -25 °C and subsequently freeze dried (scanning electron microscope, white bar = 1 mm) (from 13.67]).

Sehoof, H., Apel, J., Heschel, I., Rau, G. Influence of the freezing process on the porous structure of freeze dried collagen sponges (unpublished results, Helmholtz-Institute, Aachen, Germany... 

Nagai and Nishino [5.3] froze solutions of K2C03, Na2C03, MgS04 and A12(S04)3 18 H20 by spraying them into LN2, and freeze dried the frozen droplets at 0.13 mbar and 100 °C for 2-3 days. The dry product consisted of hollow and porous balls with a diameter from 150 to 200 pm, and had to be milled for 16 h in a ball mill to make it workable. The calcinated product had a spherical (0.1 pm diameter) or plate-like form of 0.2 to 2 pm. 

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 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. 

Fukasawa, T., Ando, M., Ohji, T. Fabrication of porous ceramics with complex pore structure by freeze drying process. Ceram. Trans. 112, Innovative Process-ing/Synthesis Ceramics, Glasses and Composites IV, 217-226, 2001... 

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