Supercritical fluid technology in particle engineering

Supercritical Fluid Technology in Particle Engineering
Ipar Nimet Uzuna*, Oya Sipahigilb, Salih Dincera a Yıldız Technical University, Faculty of Chemical and Metallurgical Engineering, Department of Chemical Engineering, 34210 Esenler, Istanbul, Turkey b Marmara University, Faculty of Pharmacy, Department of Pharmaceutical Technology, 34668 Abstract
The combination of active substances together with polymeric carrier materials to form composite particles has a great potential in pharmaceutical, cosmetic and food industries. Composite particles are generally produced either by coating a core of active substance with a polymer or dispersing it within a polymer matrix. Composite particles have several advantages such as protection and stabilization of active substances, increasing the bioavailability of poorly soluble molecules by improving solubility and design of controlled release formulations of the drugs with high water solubilities to reduce adverse side effects and improve the therapeutic efficacy [1–3]. There are several traditional methods to prepare drug-polymer composite particles such as milling, emulsion/solvent evaporation, crystallization/precipitation, phase separation, spray drying, freeze drying and interfacial polymerization. But each process has unique disadvantages which affect product quality unfavorably. In mechanical processes such as milling, thermal and frictional stresses caused by mechanical forces damage particles. Final products contain solvent residues due to excessive solvent use in emulsion/solvent evaporation and crystallization/precipitation processes necessitating further processing. Thermally labile compounds degrade because of high temperatures used in spray drying process. Supercritical particle formation processes, which can be operated in mild conditions at one stage, offer green solutions eliminating the drawbacks caused by conventional particle formation processes. Therefore, in the past two decades preparation of composite particles of drug and polymer using supercritical fluid technology has emerged as an alternative and promising method. Solubility of materials in supercritical fluid is an important parameter which must be taken into consideration when designing the processes inducing diversity in applications [4, 5]. In this work, various applications of supercritical fluid technology in particle formation were described and a special emphasis was put on two processes which supercritical carbondioxide was used: Supercritical Antisolvent (SAS) and Depressurization of an Expanded Liquid Organic Solution (DELOS). Various couples of drug (Cefuroxime Axetil-antibiotic and Paroxetine-antidepressant) and polymer (polymethylmethacrylate based polymers, polyethylene glycol, polyvinylpyrrolidone, some cellulosic polymers and beta-cyclodextrin) were coprecipitated in order to prepare drug-polymer composite particles using the two methods above. Crystallographic, morphological and dimensional properties of particles were investigated using SEM, DSC, XRD, IR and particle size analysis. Drug loadings and release profiles were determined by HPLC analysis and dissolution tests. The results were evaluated in order to compare and optimize the two methods. References
[1] M. Bahrami, S. Ranjbarian, Production of micro-and nano-composite particles by supercritical carbondioxide, J.Supercritical Fluids 40 (2007) 263– 283. [2] M. J. Cocero, A. Martin, F. Mattea, S. Varona, Encapsulation and co-precipitation processes with supercritical fluids: Fundamentals and applications, J.Supercritical Fluids 47 (2009) 546–555. [3] E. Reverchon, R. Adami, S. Cardea,G. DellaPorta, Supercritical fluids processing of polymers for pharmaceutical and medical applications, J.Supercritical Fluids 47 (2009) 484–492. [4] I. Pasquali, R. Bettini, F. Giordano, Solid-state chemistry and particle engineering with supercritical fluids in pharmaceutics, European J. Pharmaceutical Sciences 27 (2006) 299–310. [5] I. N. Uzun, O. Sipahigil, S. Dincer, Coprecipitation of CefuroximeAxetil–PVP composite microparticles by batch supercritical antisolventprocess, J.Supercritical Fluids, article in press (doi:10.1016/j.supflu.2010.09.035). Corresponding author email: Tel: 00902123834765, Fax: 00902123834725


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