A. ABD-ELBARY Original Article INCLUSION AND CHARACTERIZATION OF KETOPROFEN INTO DIFFERENT MESOPOROUS SILICA NANOPARTICLES USING THREE LOADING METHODS 1 , M. A. EL NABARAWI 1* , D. H. HASSEN 2 , A. A. TAHA 2 1 Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Kasr El- Aini Street, Cairo 11562, Egypt, 2 Department of Pharmaceutics and Industrial Pharmacy, College of Pharmacy, Misr University for Science and Technology (MUST), sixth of October city, Almotamayez District, Giza, Egypt. Received: 14 Jun 2014 Revised and Accepted: 20 Aug 2014 ABSTRACT Objective: The objective of the present study was to encapsulate ketoprofen into MCM-41, SBA-15 and uncalcined SBA-15 (unc SBA-15) using different loading methods. Investigate the effect of using different loading methods, and the effect of pore sizes on the loading capacity of mesoporous silica. Finally, determine if any changes in the mesoporous structure occurred after KP loading. Methods: Ketoprofen (KP) with about 1.5 nm molecular size was selected for encapsulation into three mesoporous silica nanoparticles (MSN). These MSN particles were selected to cover a wide range of pore diameters: MCM-41 (3.4 nm), SBA-15 (6.2 nm) and uncalcined SBA-15 (7.0 nm). Loading of KP was done by three loading methods namely rotavapor, soaking, and immersion method. The loading capacity was examined via solvent extraction. Characterization of the loaded mesoporous silica nanoparticles was done by high resolution transmission electron microscopy (HRTEM), small angle X-ray diffraction (SAXRD), nitrogen adsorption/desorption isotherms, differential scanning calorimetry (DSC), and Fourier transform infrared (FT-IR) spectroscopy. Results: KP was successfully encapsulated into MCM-41, SBA-15 and uncalcined SBA-15 without affecting the mesoporous structure. The loading process was done using three different loading methods. Rotavapor loading method yielded higher loading capacities compared to soaking and immersion method. Another important factor that affected the amount of loaded KP into MSN particles were the Pore sizes of the host particles. MCM-41, which had the smallest pore size, had the least amount of loaded drug. On the other hand, uncalcined SBA-15, which had the largest pore size, had the highest amount of loaded KP. Conclusion: This study is a promising issue for the incorporation of KP into different mesoporous silica nanoparticles. Email: nabrwima@hotmail.com Keywords: Ketoprofen, Mesoporous silica nanoparticles, MCM-41, SBA-15, Uncalcined SBA-15, Loading methods. INTRODUCTION The International Pure and Applied Chemistry (IUPAC) classified pore materials into three types: micropore material (˂ 2 nm), mesoporous material(2–50 nm) and macropore material (>50 nm). Nowadays, applications of the macroporous substances are limited owing to their low surface area and large non-uniform pores. On the contrary, numerous applications of micro- and mesoporous materials are applied due to their large surface area and uniform pore structure[1]. Silicon is the second abundant element in the earth’s crust after oxygen. Silicon occurs as oxygen containing compound termed Silicon dioxide (SiO2 2 ) which is known as silica. The first mesoporous silicananoparticles (MSN) were developed by Mobil Oil Corporation (Mobil) scientists in1992. This was named M41S series(the Mobil 41 Series), their pore diameters ranged from 15 Å and 100 Å [ , 3]. MSNs proved to bepromising candidates as drug delivery systems, they can be used either to control the release rates or to enhance the solubility of active substances[4-6]. MCM-41(Mobil Composition of Matter 41) is one of the members of M41S series. MCM-41 is characterized by uniform honeycomb structure with pore diameter that can be tailored from 20 to 100 Å. The first attempt to use MSNs as drug delivery system was done by Valet–Regi et al, where they successfully loaded ibuprofen into MCM-41[7]. SBA-15 was first reported by Zhao et al, at the University of California, Santa Barbara[8]. SBA is the abbreviation for Santa Barbara Amorphous; it is characterized by having two-dimensional hexagonal structure with pore diameters ranging from 46 to 300 Å. Ketoprofen (KP) is non steroidal anti-inflammatory drug (NSAID) belongs to the propionic acid NSAID class; its name is 2-(3-benzoyl phenyl) propionic acid. KP is a nonselective cyclooxygenase (COX) inhibitor; it has analgesic, antipyretic and antiarthritic effect through inhibiting the prostaglandin and leukotriene synthesis. KP has very strong anti-inflammatory effect which is more potent than ibuprofen, phenylbutazone and aspirin[9]. Itis used in the treatment of rheumatoid arthritis, osteoarthritis as well as in mild and moderate pain. KP is suitable for incorporation into ordered mesoporous silica having particle size about 15.3Å as well as having a carboxylic acid group, which can form hydrogen bonding with the silonal in mesoporous silica. The aim of this work is to encapsulate ketoprofen into MCM-41, SBA-15 (template occluded) and uncalcined SBA-15using different loading methods. MATERIALS AND METHODS Materials Ketoprofen was obtained as a gift sample from (Egyptian International Pharmaceutical Industries Company, Cairo, Egypt), Cetyltrimethylammonium bromide (CTAB) and Tetraethyl orthosilicate (TEOS) was obtained from (Sigma Aldrich, St. Lewis, USA), Pluronic P123 (BASF GmbH, Ludwigshafen, Germany). Other reagents and solvents were of HPLC grade. Methods Synthesis of MCM-41 MCM-41 synthesis was performed according to a previous report[10]. About 0.46 g sodium hydroxide was completely dissolved in 120 ml deionized water with stirring. After the solution became clear, 1.4 g CTAB was added and dissolved completely, 5.6 ml TEOS was poured into the above solution under vigorous stirring. Stirring continued for 24 hours and then the mixture was heated at 80 ° C for 48 hours. The mixture was filtered to obtain solid silica International Journal of Pharmacy and Pharmaceutical Sciences ISSN- 0975-1491 Vol 6, Issue 9, 2014 Innovare Academic Sciences