Volume 3(1): 011-015 (2011) - 011 J Bioequiv Availab ISSN:0975-0851 JBB, an open access journal Open Access Nanjwade et al. J Bioequiv Availab 2011, 3:1 DOI: 10.4172/jbb.1000050 Open Access Research Article Keywords: Sirolimus; Immunosuppressant; Solid lipid microparticulates; Hot homogenization technique; Biocompatible lipid microparticles; Glyceryl monostearate Introduction Sirolimus (Rapamycin, Rapammune) is a macrolide lactone produced by streptomyces hydroscopicus. It is an immunosupressive agent used for the prophylaxis of renal allograf rejection. Te drug was frst isolated from a soil sample from Rapa Nui, an island in the south pacifc, hence the prefx “Rapa”. It is extremely hydrophobic having molecular weight 914.2 g/mol [1,2,3]. Sirolimus is neither calcineurin inhibitor (as are cyclosporine and tacrolimus) nor an anti metabolite (as are mycophenolate mofetil and azathioprine). Sirolimus has a novel mechanism of immunosuppressant action involving the suppression of T-lymphocyte proliferation through inhibition of the target of rapamycin protein kinase complex (TORC) [4]. Mammalian TORC is critical for cell cycle progression and cell proliferation. Blockade of TORC inhibits cytokine-mediated proliferation in T cells, B cells and mesenchymal cells, including smooth muscle cells [5]. In recent years, biocompatible lipid micro- and nanoparticles have been reported as potential drug carrier systems as alternative materials to polymers [6]. Tey can be considered as physiologically compatible, physicochemically stable and allowing a large-scale production at a relative low production cost than liposomes [7]. Tese micrometer-sized particles consist of a solid fat core based on naturally occurring lipids and stabilized by a layer of surfactant molecules on the surface [8]. SLM are characterized by their better bio-compatibility as compared to competing polymeric microparticles [9]. Solid lipid micro- or nanoparticles are in the form of solid lipids and provide an alternative option for encapsulating lipophilic compounds. Protein stabilization could be achieved by a suitable particle formulation or a polymer mixture [10]. Diferent methods can be adopted to prepare solid lipid micro- or nanoparticles. In one of the study, modifed high shear homogenization and ultrasound method was utilized to formulate SLNs [11]. Reithmeier H and co- workers [12,13] in two diferent studies prepared peptide containing glyceryl palmitate microparticles as well as lipid microparticles by using modifed solvent evaporation method and a melt dispersion technique without the use of organic solvent. In this study, we prepared solid lipid microparticles by hot homogenization method [14,15]. Te main aim of this investigation was to develop and evaluate solid lipid microparticles of sirolimus for oral delivery. Te proposed sirolimus concentration in this formulation was chosen afer assay and moisture content correction of API (sirolimus). Furthermore, in the present investigation, we aimed at fabricating SLM of sirolimus by using hot homogenization method and with easily available solid lipids such as glyceryl monostearate (GMS) and characterized it for assay and in vitro release. Materials and Methods Materials Sirolimus (Zydus Cadila, Ahmedabad); Glyceryl monostearate (Fine organics Ltd., Mumbai, India); Sodium taurocholate, Acetone, Ethanol (All AR grade) and Acetonitile (ACN), H 3 PO 4 (HPLC grade) were purchased from S.D. fne chemicals (Mumbai, India). All the excipients and reagents were used as received. Double distilled water was prepared freshly when ever required. Preparation of solid lipid microparticles Solid lipid microparticles were prepared by a hot homogenization technique. Te formulations were optimized by frst preparing blank microparticles by varying the content of GMS and sodium taurocholate and also by varying the processing parameters as shown in Table 1 and 2. Blank SLMs were prepared by frst dissolving GMS in a mixture *Corresponding author: Dr. Basavaraj K. Nanjwade, Department of Pharmaceutics, KLE University College of Pharmacy, BELGAUM, INDIA – 590010, Tel: 00919742431000; Fax: 00918312472387; E-Mail: bknanjwade@yahoo.com Received December 07, 2010; Accepted January 24, 2011; Published February 01, 2011 Citation: Nanjwade BK, Patel DJ, Parikh KA, Nanjwade VK, Manvi FV (2011) Development and Characterization of Solid-Lipid Microparticles of Highly Insoluble Drug Sirolimus. J Bioequiv Availab 3: 011-015. doi:10.4172/jbb.1000050 Copyright: © 2011 Nanjwade BK, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Abstract Solid lipid microparticles (SLMs) represent an alternative carrier system to traditional colloidal carrier such as emulsion, liposomes and polymeric micro and nanoparticles. The purpose of this research work was to develop and evaluate solid lipid microparticles of sirolimus for oral delivery. Sirolimus is an immunosupressive drug used to prevent transplant rejection and to treat auto immune diseases. It is a macrolide lactone produced by streptomyces hydroscopicus. It is extremely hydrophobic. Sirolimus solid lipid microparticles were prepared by hot homogenization technique. The matrix chiefy consisted of glyceryl monostearate and sodium taurocholate. The SLMs were studied for its particle size analysis, drug content, entrapment effciency, in vitro release characteristics and also for stability analysis at different temperature and humidity conditions. Average particle size was found to be 21.40µm. Drug content of SLMs determined by HPLC analysis was found to be 98.6±0.31% while entrapment effciency achieved was 98.02%. Drug release from the fnal formulation was found to be 90.3% in 90 min. SLMs formulated with glyceryl monostearate and sodium taurocholate can be used for oral delivery of hydrophobic drugs with in-vivo study still to be explored. Development and Characterization of Solid-Lipid Microparticles of Highly Insoluble Drug Sirolimus Basavaraj K. Nanjwade*, Didhija J. Patel, Kemy A. Parikh, Veerendra K. Nanjwade and F. V. Manvi Department of Pharmaceutics, KLE University College of Pharmacy, Belgaum, India Journal of Bioequivalence & Bioavailability J o u r n a l o f B i o e q u iv a l e n c e & B i o a v a i l a b i l i t y ISSN: 0975-0851