Abstract
Most of the novel highly potent drugs, developed on the basis of modern molecular medicine, taking into account cell surface recognition techniques, show poor water solubility. A chemical modification of the drug substance enhancing the solubility often decreases the pharmacological activity. Thus, as an alternative an increase of the solubility can be obtained by the reduction of the size of the drug particles. Unfortunately, it is often difficult to obtain micro or nanosized drug particles by classical or more advanced crystallization using supercritical gases or by milling techniques. In addition, nanosized particles are often not physically stable and need to be stabilized in an appropriate matrix. Thus, it may be of interest to manufacture directly nanosized drug particles stabilized in an inert hydrophilic matrix, i.e. nanostructured and nanocomposite systems. Solid solutions and solid dispersions represent nanostructured and nanocomposite systems. In this context, the use of the vacuum-fluidized-bed technique for the spray-drying of a low water soluble drug cosolubilized with a hydrophilic excipient in a polar organic solvent is discussed. In order to avoid the use of organic solvents, a special spray-freeze-drying technique working at atmospheric pressure is presented. This process is very suitable for temperature and otherwise sensitive drugs such as pharmaproteins.
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References
Benet L.Z., C.-Y.Wu, M.F. Herbert &; V.J.Wacher, 1996. Intestinal drug metabolism and antitransport processes. A potential paradigm shift in oral drug delivery. J. Contr. Release 39, 139-1143.
Bongartz C., 2002. PhD Thesis, University of Basel (to be published).
Chiou W.L. &; S. Riegelmann, 1971. Absorption characteristics of solid dispersed and micronized Griseofulvin in man. J. Pharm. Sci. 60, 1376-1380.
Chiou W.L. &; S. Niazi, 1976. Pharmaceutical applications of solid dispersion systems: Dissolution of Griseofulvin-Succinic acid eutectic mixture. J. Pharm. Sci. 65, 1212-1214.
Chiou W.L. &; S. Riegelmann, 1969. Preparation and dissolution characteristics of several fast-release solid dispersions of griseofulvin. J. Pharm. Sci. 58, 1505-1510.
Friömming K.-H., K. Heyer &; R. Hosemann, 1981. Schmelzeinbettung des Griseofulvins in Pluronic F68, Deutsche Apoth. Zeitung 121, 2276-2280.
Geldart D., N. Harby &; A.C. Wong, 1983. Fluidization of cohesive powders in 'The role of particle interactions' in powder mechanics, preprint of Int. Symp. Eindhoven, August 29-31, p. 24.
Komiyama H., K. Sunouchi, Y. Egashira &; Y. Shimogaki, 1990. Mechanism of particle formation in chemically reactive systems. In: Proceedings of Second World Congress Particle Technology, Society of Powder Technology, September 19-22, Kyoto, Japan, Vol. II, pp. 245-256.
Leuenberger H., B. Luy &; P. Hirschfeld, 1990. Experiences with a novel fluidized bed system operating under vacuum conditions. In: Proceedings of Preworld Congress Particle Technology, September 17-18, pp. 113-122, Gifu, Japan.
Lindenbaum J., J.R. Butler, J.E. Murphy &; R.M. Cresswell, 1973. Correlation of digoxin-tablet dissolution rate with biological availability. Lancet 1, 1215-1217.
Luy B., P. Hirschfeld &; H. Leuenberger, 1989a. Granulation and Drying inVacuum Fluid Bed Systems, Drugs made in Germany, 32, 3-8.
Luy B., P. Hirschfeld &; H. Leuenberger, 1989b. Granulieren und Trocknen in der Vakuum-Wirbelschicht. Pharm. Ind. 51, 89-94.
Maung M.C., K. Patel &; R.T. Borchardt, 1989. Stability of protein pharmaceuticals. Pharm. Res. 11, 903-918.
Mennet H.P., 1994. Sprüh-Gefriertrocknung bei Atmosph ¨arendruck: Ein Beitrag zur Untersuchung des Prozesses und seiner Anwendungsmöglichkeiten, PhD Thesis, University of Basel.
Mumenthaler M. &; H. Leuenberger, 1991. Atmospheric sprayfreeze drying: A suitable alternative in freeze drying technology. Int. J. Pharm. 72, 97-110.
Pikal M.J., M.L. Roy &; S. Shah, 1984. Mass and heat transfer in vial freeze-drying of pharmaceuticals: Role of the vial. J. Pharm. Sci. 73, 1224-1237.
Pikal M.J., K.M. Dellerman, M.L. Roy &; R.M. Riggin, 1991. The effect of formulation variables on the stability of freeze-dried human growth hormone. Pharm. Res. 8, 427-436.
Robertson J., M.B. King, J.P.K. Seville, D.R. Merrifield &; P.C. Buxton, 1998. Recrystallization of Organic Compounds Using Near critical Carbon Dioxide, Preprints of the 1st European Symposium Process Technology in Pharmaceutical and Nutritional Sciences, PARTEC 98, 10-12 March, Nürnberg, Germany (H. Leuenberger, ed.), pp. 131-140. ISBN 3-921590-55-8.
Shaw T.R.D. &; J.E. Careless, 1974. Effect of particle size on the absorption of digoxine. Eur. J. Clin. Pharmacol. 7, 269-273.
Soldner A., U. Christians, M. Susanto, V.J. Wacher, J.A. Silverman &; L.Z. Benet, 1999. Grapefruit Juice activates P-Glycoprotein-mediated drug transport. Pharm. Res. 16, 478-485.
Stella B, S. Arpicco, M.T. Peracchia, D. Desmaele, J. Hoebeke, M. Renoir, J. D'Angelo, I. Cattel &; P. Couvreur, 2000. Design of folic acid-conjugated nanoparticles for drug targeting. J. Pharm. Sci. 89, 1452-1464.
Tanaka T, 1995. Optimum design for fine and ultrafine grinding mechanisms using grinding media. KONA 13, 19-29.
Weber A, J. Tschernjaew, M. Beutin &; R. Kümmel, 1998. Fine particle production by precipitation with compressed or supercritical fluids, Preprints of the 1st European Symposium Process Technology in Pharmaceutical and Nutritional Sciences, PARTEC 98, 10-12 March, Nürnberg, Germany (H. Leuenberger, ed.), pp. 121-130. ISBN 3-921590-55-8.
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Leuenberger, H. Spray Freeze-drying – The Process of Choice for Low Water Soluble Drugs?. Journal of Nanoparticle Research 4, 111–119 (2002). https://doi.org/10.1023/A:1020135603052
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DOI: https://doi.org/10.1023/A:1020135603052