Indo. J. Chem., 2010, 10 (3), 269 - 275 269 DIFFUSION BEHAVIOR OF KETOPROFEN THROUGH CHITOSAN-ALGINATE MEMBRANES Purwantiningsih Sugita*, Rini Siswati Asnel, Budi Arifin, and Tuti Wukirsari Department of Chemistry, Bogor Agricultural University, Gedung Fapet W2 Lt 4-5, Jl. Agatis Kampus IPB Darmaga, Indonesia Received July 27, 2010; Accepted August 5, 2010 ABSTRACT Chitosan-alginate membrane diffusion behavior has been investigated for its application in drugs delivery system. Ketoprofen diffusion behavior assay were performed at 37 and 42 °C to membrane thickness (h) and donor cell concentration of ketoprofen variations (A). The results showed that equilibrium concentrations (C s ) of ketoprofen equation was 27.0087 + 0.09067T − 1.7499h + 0.1030A + 0.0161h 2 − 0.0022A 2 + 0.0040Th − 0.0018TA + 0.0095hA. The value of C s was closer to the expected therapy concentration at 50 and 75 mg/L with thin membrane (10-34 μm). Based on Higuchi equation, the model for J and D were J = 11.0849 – 0.2713T – 0.3132h – 0.7461C s – 0.0096A – 0.0001h 2 – 0.0131C s 2 + 0.0002A 2 + 0.0084Th + 0.0275TC s – 0.0018TA – 0.0059hC s + 0.0021hA + 0.0037C s A with R 2 = 97.9% and D = –12.5000 + 0.2266T + 0.1313h + 0.1538C s + 0.1200A − 0.0009h 2 + 0.0240 C s 2 − 0.0009A 2 + 0.0015Th − 0.0150 TC s − 0.0011TA – 0.0096hC s + 0.0004hA + 0.0039C s A with R 2 = 98.7%, respectively. The two dimensional contour maps of J versus A and h, both at 37 and 42 °C, showed an increasing of J value as A, h, or T increased. Keywords: ketoprofen, chitosan-alginate, diffusion INTRODUCTION The ability of chitosan to form membrane has been much studied. The membranes chitosan are potential to be used in drug delivery systems. Yamada et al. [1] and Sutriyo et al. [2] have coated ketoprofen anti- inflammatory drugs and propranolol hydrochloride anti- hypertension drugs by chitosan membranes, respectively. However, its fragile membrane property needs to be strengthened by adding glutaraldehyde as a cross-linker and natural or synthetic polymer as an interpenetrating agent. Sugita et al. have been investigated chitosan modified membranes by adding glutaraldehyde and natural hydrocolloid like guar gum [3], alginate [4], carboxymethylcelullose (cmc) [5] and xanthan gum [6], respectively. The chitosan modified are potential for membranes to be used in drug delivery systems. The potential of chitosan-guar gum membranes as drug delivery system have investigated by Nata et al. [7] and Sugita et al. [8] through such ketoprofen diffusion and in vitro dissolution behaviors, respectively. * Corresponding author. Email address : ugiet@yahoo.com Nata et al. [7] reported that ketoprofen diffusion through such chitosan-guar gum membrane was initiated by swelling process followed with membrane pores opening that release the drugs content from the matrix. Sugita et al. [8] reported that microphotographs of ketoprofen microcapsules in the gastrointestinal (KCl- HCl solution, pH 1.2) after 30 min of dissolution were shattered, so ketoprofen release became uncontrollable. Guar gum was not hold out to acid solution at pH < 3.0. Microphotographs of ketoprofen microcapsules in the intestinal (buffer phosphate solution, pH 7.4) after 90 min of dissolution were still controllable and coated of ketoprofen content about 31.5%, but release time was too fast. On the other hand, shelf life of microcapsules are about 18.92 months if kept in climatic chamber at (40 ± 2) °C and RH (75 ± 5)% for 3 months [9]. Herdini [10] have been used chitosan-alginate membranes as drug delivery system for curcuma. Sarmento et al. [11], Van den Berg et al. [12], and Pandey & Khuller [13] have also used it for coating insulin hormone, protein, and antibiotics drug (like riphamicyne, isonyazide tuberculosis, pirazynamide), respectively. The membranes were applicable as coating material on slow-released drug preparation and hold out to acid solution at pH < 3.0 [14]. In previous research, Sugita et al. [4] reported that the membrane is also potential for membranes to be used in drug delivery systems. In this research, the membranes could be used to coat a ketoprofen. This membrane has not been investigated practically. Ketoprofen is a non-steroid anti-inflammatory drug (NSAID) with poor- solubility in water. Serious gastrointestinal toxicity, such as bleeding, ulceration, and perforation, can occur in patients treated chronically with ketoprofen therapy. This weakness can be overcome by microencapsulation the ketoprofen. It is hoped that the microcapsule can control the released of the ketoprofen. Chitosan-alginate membranes are expected to be more effectively coat and control the drug release. Purwantiningsih Sugita et al.