Characterization of New Topical Ketoprofen Formulations Prepared by Drug Entrapment in Solid Lipid Matrices ANNA ARGEM ´ I, 1 CONCEPCI ´ ON DOMINGO, 2 ANA RAQUEL SAMPAIO DE SOUSA, 3 CATARINA M. M. DUARTE, 3,4 CARLOS A. GARC ´ IA-GONZ ´ ALEZ, 2 JAVIER SAURINA 1 1 Department of Analytical Chemistry, University of Barcelona, E-08028 Barcelona, Spain 2 Instituto de Ciencia de Materiales de Barcelona (CSIC), Campus de la UAB s/n, E-08193 Bellaterra, Spain 3 Instituto de Biologia Experimental e Tecnol´ ogica (IBET), 2781-901 Oeiras, Portugal 4 Instituto de Tecnologia Qu´ ımica e Biol ´ ogica (ITQB), 2780-157 Oeiras, Portugal Received 10 March 2011; revised 11 May 2011; accepted 9 June 2011 Published online 24 June 2011 in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/jps.22684 ABSTRACT: This paper describes the evaluation of a new pharmaceutical formulation based on ketoprofen entrapment in a solid lipid particle (SLP) matrix. The drug–SLP samples, which were elaborated using a processing technology based on supercritical CO 2 , consisted of a model of a controlled-release system for topical applications. Some of the samples contained silanized TiO 2 as an additional ingredient to increase the interaction between drug and lipid matrix. The study of the sample features relied on reversed-phase high-performance liquid chromatography with a C 18 column and ultraviolet spectroscopic detection at 266 nm. Characterization assays comprised the determination of the overall amount of ketoprofen in the samples, the assessment of the release–permeation kinetic profiles, and the evaluation of impurities and decomposition products. The release and permeation of encapsulated ketoprofen were assayed at 32 ◦ C and pH 6.8 by using a static diffusion cell. Results showed a sustained drug delivery for at least 24 h. Besides, no degradation species were detected throughout the release–permeation processes, which indicated that the stability of the drug in the SLP system was preserved. © 2011 Wiley- Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:4783–4789, 2011 Keywords: ketoprofen determination; HPLC–UV; solid lipid particles; controlled release; microencapsulation; diffusion cell; in-vitro models; kinetics INTRODUCTION The administration of drugs via the skin is increas- ingly exploited for both topical and transdermal treat- ments. The encapsulation of active agents is regarded as a technological solution to stabilize the drug, to op- timize the release pattern, and to enhance penetra- tion in transdermal delivery. 1 Ketoprofen is a therapeutic agent with anti- inflammatory, antipyretic, and analgesic activity that has been selected in this paper as a model compound for the preparation of controlled delivery systems for topical and transdermal applications. Ketoprofen is usually administered topically to treat musculoskele- tal disorders such as rheumatoid arthritis and os- Correspondence to: Javier Saurina (Telephone: +34 93 4039778; Fax: +34 93 4021233; E-mail: xavi.saurina@ub.edu) Journal of Pharmaceutical Sciences, Vol. 100, 4783–4789 (2011) © 2011 Wiley-Liss, Inc. and the American Pharmacists Association teoarthritis. The physicochemical characteristics of this molecule regarding lipophilicity (log P = 2.8) and molecular weight are adequate for penetration through the human stratum corneum. 2,3 Lipid-based matrices are often used to encapsu- late lipophilic topical and transdermal drugs 4,5 be- cause they may serve as drug carriers as well as drug localizers. Among them, solid lipid particles (SLPs) provide good properties for the elaboration of controlled-release systems, 6–8 excellent tolerability, 9 protection of active compounds against chemical decomposition, 10,11 and physical stability. 12 A lipid matrix consisting of a mixture of hydro- genated castor oil and glyceryl monostearate has been used in this paper to tackle the ketoprofen encapsula- tion. The physicochemical characteristics of the mix- ture of these lipids are suitable for the preparation of SLPs for pharmaceutical and cosmetic applications. 10 In addition, nanoparticles of TiO 2 and silanized TiO 2 JOURNAL OF PHARMACEUTICAL SCIENCES, VOL. 100, NO. 11, NOVEMBER 2011 4783