International Journal of Pharmaceutics 358 (2008) 292–295 Contents lists available at ScienceDirect International Journal of Pharmaceutics journal homepage: www.elsevier.com/locate/ijpharm Note Nanocapsule@xerogel microparticles containing sodium diclofenac: A new strategy to control the release of drugs Let´ ıcia Sias da Fonseca a , Rodrigo Paulo Silveira a , Alberto Marc ¸ al Deboni a , Edilson Valmir Benvenutti a , Tˆ ania M.H. Costa a , S´ ılvia S. Guterres b , Adriana R. Pohlmann a,∗ a Programa de P´ os-Graduac ¸˜ ao em Qu´ ımica, Instituto de Qu´ ımica, Universidade Federal do Rio Grande do Sul, CP 15003, Porto Alegre 91501-970, RS, Brazil b Programa de P´ os-Graduac ¸˜ ao em Ciˆ encias Farmacˆ euticas, Faculdade de Farm´ acia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil article info Article history: Received 10 January 2008 Received in revised form 6 February 2008 Accepted 7 February 2008 Available online 15 February 2008 Keywords: Nanoparticle-coated microparticles Nanocapsule-coated xerogels Sol–gel Spray-drying Sodium diclofenac abstract The aim of this work was to evaluate the potentiality to control the drug release of a new architecture of microparticles organized at the nanoscopic scale by assembling polymeric nanocapsules at the surface of drug-loaded xerogels. Xerogel was prepared by sol–gel method using sodium diclofenac, as hydrophilic drug model, and coated by spray-drying. After coating, the surface areas decreased from 82 to 28m 2 /g, the encapsulation efficiency was 71% and SEM analysis showed irregular microparticles coated by the nanocapsules. Formulation showed satisfactory gastro-resistance presenting drug release lower than 3% (60 min) in acid medium. In water, the pure drug dissolved 92% after 5 min, uncoated drug-loaded xero- gel released 60% and nanocapsule coated drug-loaded xerogel 36%. After 60 min, uncoated drug-loaded xerogel released 82% and nanocapsule coated drug-loaded xerogel 62%. In conclusion, the new system was able to control the release of the hydrophilic drug model. © 2008 Elsevier B.V. All rights reserved. Microparticles have been extensively studied in the past 30 years. Their advantages, among others, are: ready distribution, higher bioavailability and accuracy in reproducibility dose by dose, more constant drug plasma levels, minor risk of toxicity due to the dose dumping, gastrointestinal tract protection and labile drug protection in the gastrointestinal tract (Benita, 1996). To prepare microparticles, the spray-drying technique exhibits advantages such as rapid and one step process, low cost and ease of industrial transposition (Wan et al., 1992). Nanoparticles have also been widely studied as drug carriers (Couvreur et al., 2002). Their main advantages are drug sustained release, increase of drug selectivity and effectiveness, improvement of drug bioavailability and decrease of drug toxicity. Polymeric nanoparticles are named nanocapsules, when they contain a poly- meric wall and an oil core (J¨ ager et al., 2007), or nanospheres, when they are formed by polymeric matrix stabilized by surfac- tants (Pohlmann et al., 2007). The spray-drying technique has been employed to dry nanoparticles improving their physico-chemical stability (Guterres et al., 2000). Powders have been obtained using Aerosil 200 ® , as drying adjuvant (Guterres et al., 2001)(Fig. 1a). The spray-drying technique has also been used to prepare organic–inorganic systems, in which the drug was dispersed in ∗ Corresponding author. Tel.: +55 51 33087237; fax: +55 51 33087304. E-mail address: pohlmann@iq.ufrgs.br (A.R. Pohlmann). agglomerates of Aerosil 200 ® , the inorganic phase, and the poly- meric nanoparticles were used as coating material (Beck et al., 2004)(Fig. 1b). The Aerosil 200 ® is an agglomerate of non-porous primary silica particles about 40 nm. So, the drug is entrapped in the silica macropores. Drug-loaded porous silica microparticles have been synthesized by sol–gel method (Unger et al., 1983), which is based on the catalyzed hydrolysis and condensation of alkoxysilanes giving a cross-linked network (Novak, 1993). The sol–gel method forms an inorganic matrix (xerogel silica) under soft conditions and low tem- perature allowing the incorporation of labile molecules in the gel (Santos et al., 1999). Two methods for drug incorporation in the xerogel have been used: drug incubation (Ahola et al., 1999) and the drug in situ incorporation (Kortesuo et al., 2000). The use of xerogels instead of Aerosil 200 ® to encapsulate drugs could have the advantage of delaying the drug release because the drug is also encapsulated in the mesoporous besides its encapsu- lation in the xerogel macropores. To diminish the burst release of drugs from xerogel mesopores, different strategies have been pro- posed (Slowing et al., 2007). Our strategy to avoid a high burst release is based on the use of polymeric nanocapsules as coating material for the agglomerates of drug-loaded xerogel. This complex architecture (Fig. 1c) considers that the polymeric nanocapsules are hydrophobic and, as a consequence, they could retard the contact of the microparticles with water (continuous phase), avoiding a burst and delaying the drug release. 0378-5173/$ – see front matter © 2008 Elsevier B.V. All rights reserved. doi:10.1016/j.ijpharm.2008.02.005