Spray-Freezing into Liquid

The spray freezing into liquid (SFL) process creates micronized powders with enhanced dissolution rates... 

Yu, Z. Garcia, A.S. Johnston, K.P. Williams I., Robert O. Spray freezing into liquid nitrogen for highly stable protein nano structured microparticles. Eur. J. Pharm. Biopharm. 2004, 58 (3), 529-537. 

Johnston, K.P. Williams, R.O. Enhanced aqueous dissolution of a poorly water soluble drug by novel particle 75. engineering technology spray-freezing into liquid with atmospheric freeze-drying. Pharm. Res. 2003, 20 (3),... 

Yu ZC, Rogers TL, Hu JH, Johnston KP, Williams RO. Preparation and characterization of microparticles produced by a novel process spray freezing into liquid. Eur J Pharm Biopharm 2002 54 221-228. 

A variation of this process is spray freezing into liquid, where the impingement of the feed solution onto the cryogenic liquid results in intense atomization into... 

Vaughn JM, Gao X, Yacaman MJ, Johnston KP, Williams RO HI (2005) Comparison of powder produced by evaporative precipitation into aqueous solution (EPAS) and spray freezing into liquid (SFL) technologies using novel Z-contiast STEM and complimentary techniques. Eur J Pharm Biopharm 60(l) 81-89... 

Hu J, Rogers TL, Brown J, Young T, Johnston KP, Williams RO. Improvement of dissolution rates of poorly water soluble APIs using novel spray freezing into liquid technology. Pharm Res 2002 19(9) 1278-1284. 

Rogers TL, Johnston KP, Williams RO. Physical stability of micronized powders produced by spray-freezing into liquid (SFL) to enhance the dissolution of an insoluble drug. Pharm Dev Technol 2003 8(2) 187-197. 

Spray freezing into liquid (SEE) evaporative precipitation into aqueous solution (EPAS) and... 

Identification of radical 3 as a species that is present in the steady-state phase of the reaction does not prove that it is an intermediate—it could be a species that is peripheral to the real reaction mechanism. Proof that a species is an intermediate requires a demonstration that it is kinetically competent to participate in the mechanism. In the case of a metastable radical, the usual procedure is to conduct transient kinetic studies using a rapid mixing apparatus equipped to quench samples by spraying them into liquid isopentane. The frozen aqueous samples (snows) from the timed cold quenches are then packed into EPR tubes and analyzed spectroscopically. Simple mixing of enzyme with SAM and lysine followed by freeze-quenching on the millisecond time scale does not work because the activation by SAM takes about 5 s. However, a preliminary mix of enzyme with SAM and [2- C]lysine, aging of the solution for 5 s within the apparatus. 

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). 

The freezing of a slice of beef in direct contact with a model liquid has been used to demonstrate the influence of the two terms w and u. To freeze a product for freeze-drying, two methods are mainly used (i) freezing of the product in trays or in vials on cooled surfaces or (ii) in a flow of cold air. If these methods do not result in a sufficient freezing rate, liquid nitrogen (LN2) in direct contact with the vials is used (see Figures 2.2.1 and 2.2.2) or droplets of the product are sprayed into LN2 (see Section 2.1.4). 

Another freezing technique involves spraying the solution directly into liquid The lower temperature could promote more rapid freezing, but this potential advantage is offset by poor thermal contact of the solution with the liquid N2, due to an insulting layer of gas around the solution droplets. A pneumatic rather than hydraulic nozzle can also be used to disperse the solution into a fine aerosol whose droplets can be frozen quickly because of their small size. This technique is less manageable because it is difficult to separate the fine aerosol droplets from the gas before freezing. 

The advantages of spray-freezing tmd jet-freezing were combined in such a way that the sample which is sandwiched between two copper plates is shot into liquid propane. Recently a new device was developed in which the freezing can be done in a very controlled way and which can also be used for metal mirror freezing [27]. 

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