Cryogenic liquids, nanoparticles, and microencapsulation - Spray Freeze-Drying

Cryogenic liquids, nanoparticles, and microencapsulation
Received 22 March 2006; revised 23 March 2006; accepted 21 April 2006. Available online 28 April 2006.
Troy Purvisa, Jason M. Vaughna, b, True L. Rogersa, b, Xiaoxia Chena, b, Kirk A. Overhoffa, Prapasri Sinswata, Jiahui Hua, b, Jason T. McConvillea, Keith P. Johnstonb, , and Robert O. Williams IIIa
International Journal of Pharmaceutics
Volume 324, Issue 1 , 31 October 2006
ScienceDirect
Copyright ? 2006 Elsevier B.V. All rights reserved.
aCollege of Pharmacy, University of Texas at Austin, Austin, TX 78712, USA
bDepartment of Chemical Engineering, University of Texas at Austin, Austin, TX 78712, USA
Abstract
The biopharmaceutical classification system (BCS) is used to group pharmaceutical actives depending upon the solubility and permeability characteristics of the drug. BCS class II compounds are poorly soluble but highly permeable, exhibiting bioavailability that is limited by dissolution. The dissolution rate of BCS class II drug substances may be accelerated by enhancing the wetting of the bulk powder and by reducing the primary particle size of the drug to increase the surface area. These goals may be achieved by nucleating drug particles from solution in the presence of stabilizing excipients. In the spray freezing into liquid (SFL) process, a drug containing solution is atomized and frozen rapidly to engineer porous amorphous drug/excipient particles with high surface areas and dissolution rates. Aqueous suspensions of nanostructured particles may be produced from organic solutions by evaporative precipitation into aqueous solution (EPAS). The suspensions may be dried by lyophilization. The particle size and morphology may be controlled by the type and level of stabilizers. In vivo studies have shown increased bioavailability of a wide variety of drugs particles formed by SFL or EPAS. For both processes, increased serum levels of danazol (DAN) were observed in mice relative to bulk DAN and the commercial product, Danocrine?. Orally dosed itraconazole (ITZ) compositions, formed by SFL, produce higher serum levels of the drug compared to the commercial product, Sporanox? oral solution. Additionally, nebulized SFL processed ITZ particles suspended in normal saline have been dosed via the pulmonary route and led to extended survival times for mice inoculated with Aspergillis flavus. SFL and EPAS processes produce amorphous drug particles with increased wetting and dissolution rates, which will subsequently supersaturate biological fluids in vivo, resulting in increased drug bioavailability and efficacy.
Keywords: Spray-freezing into liquid (SFL); Evaporative precipitation into aqueous solution (EPAS); Poorly water soluble drugs; Oral delivery; Bioavailability; Pulmonary delivery

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Corresponding author at: College of Pharmacy, Mailstop A1920, University of Texas at Austin, Austin, TX 78712, USA. Tel.: +1 512 471 4681; fax: +1 512 471 7474.
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