Controlled Release of Diclofenac Sodium and Ibuprofen through Beads of Sodium Alginate and Hydroxy Ethyl Cellulose Blends K. S. V. Krishna Rao, 1 M. C. S. Subha, 1 B. Vijaya Kumar Naidu, 2 M. Sairam, 2 N. N. Mallikarjuna, 3 T. M. Aminabhavi 2 1 Department of Chemistry, Sri Krishnadevaraya University, Anantapur 515003, Andhra Pradesh, India 2 Drug Delivery Division, Center of Excellence in Polymer Science, Karnatak University, Dharwad 580 003, Karnataka, India 3 US Environmental Protection Agency, Cincinnati, Ohio Received 19 November 2005; accepted 16 March 2006 DOI 10.1002/app.25087 Published online in Wiley InterScience (www.interscience.wiley.com). ABSTRACT: Controlled release of diclofenac sodium (DS) and ibuprofen (IB) drugs through sodium alginate (NaAlg)- hydroxy ethyl cellulose (HEC) blend polymeric beads has been investigated. Beads were prepared by precipitating the viscous solution of NaAlg and HEC blend in alcohol fol- lowed by crosslinking with calcium chloride. Different for- mulations were developed in bead form by varying the amount of HEC, crosslinking agent, and drug concentration. Swelling studies in water, percent encapsulation of drugs, and release studies were carried out. The DS-loaded beads have shown better release performance than the IB-loaded beads. Diffusion parameters were evaluated from the Fick- ian diffusion theory. Mathematical modeling studies and drug release characteristics through bead matrices were studied by solving Fick’s diffusion equation. The results are discussed in terms of drug release patterns and theoretical concentration profiles generated through matrices, consider- ing spherical geometry of the beads. Ó 2006 Wiley Periodicals, Inc. J Appl Polym Sci 102: 5708–5718, 2006 Key words: sodium alginate; hydroxy ethyl cellulose; diclo- fenac sodium; ibuprofen; controlled release INTRODUCTION In the literature of pharmaceutics, a variety of poly- mers have been used for developing controlled release (CR) formulations to enhance the release rates of drugs. Among various polymers employed, hydro- philic biopolymers are quite suitable in oral applica- tions because of their inherent advantages over the synthetic polymers. Sodium alginate (NaAlg), a natu- ral polysaccharide, can be derived from brown sea- weeds. It is composed of D-mannuronic acid and D- guluronic acid. This polysaccharide is extensively used in food industry as a gelling agent and for encap- sulating living cells. 1–3 Because the polymer is biode- gradable and biocompatible and can be used in drug delivery applications. 4–7 There are many applications of NaAlg in agriculture 2,8,9 when it is crosslinked with glutaraldehyde. Hydroxy ethyl cellulose (HEC), a nonionic water-soluble and water-swellable cellulose ether, is compatible with a wide range of other water- soluble polymers. 6,10,11 It is commercially used in paints, paper finishes, and membrane designing. 10 From a perusal of the literature, it is found that no studies have been made on the blends of NaAlg with HEC to study the CR of nonsteroidal antiinflammatory (NASID) drugs. This prompted us to undertake a detailed study on two model drugs, viz., diclofenac so- dium (DS), a water-soluble drug, and ibuprofen (IB), a water insoluble drug. Both the drugs have antiinflam- matory properties and are used in the treatment of rheumatoid arthritis, osteoarthritis, and anlylosing spondylitis for the quick relief of pain. 3,12 Both the drugs are readily absorbed throughout the gastrointes- tinal tract (GIT). Of these, elimination of IB is some- what rapid after administration. To avoid the side effects of DS and IB caused by the high plasma peaks, we have attempted here to develop their CR formula- tions with NaAlg. Earlier, CR of antihypertensive drugs through the tableted microspheres of cellulose derivatives has been reported. 10,12,13 In continuation of our ongoing program of research, 7,12,14 we now report in vitro results on the CR of DS and IB drugs through the beads prepared from NaAlg and HEC polymers blends in different combinations. The effect of HEC content, crosslinking agent, and drug concentrations on the release rates of DS and IB are discussed. Mathe- matical modeling and drug release characteristics have This article is CEPS communication No # 53. Correspondence to: T. M. Aminabhavi (aminabhavi@yahoo. com). Contract grant sponsor: University Grants Commission (UGC), New Delhi; contract grant numbers: F1-41/2001/ CPP-II and F 12-202002/(SR-I). Journal of Applied Polymer Science, Vol. 102, 5708–5718 (2006) V V C 2006 Wiley Periodicals, Inc.