International Journal of Biological Macromolecules 74 (2015) 310–317 Contents lists available at ScienceDirect International Journal of Biological Macromolecules j ourna l ho me pa g e: www.elsevier.com/locate/ijbiomac Chitosan cocrystals embedded alginate beads for enhancing the solubility and bioavailability of aceclofenac Mani Ganesh a,∗ , Ung Jin Jeon a , Udhumansha Ubaidulla b , Pushparaj Hemalatha a , Arthanari Saravanakumar a , Mei Mei Peng a , Hyun Tae Jang a,∗ a Department of Chemical Engineering, Hanseo University, 360 Daegok-ri, Haemi-myun, Seoson-Si 356706, Chungcheongnam-do, Republic of Korea b Department of Pharmaceutics, C.L. Baid Metha College of Pharmacy, Chennai, India a r t i c l e i n f o Article history: Received 20 November 2014 Received in revised form 13 December 2014 Accepted 24 December 2014 Available online 31 December 2014 Keywords: Aceclofenac Cocrystal Sustained release SDDS Anti-inflammatory a b s t r a c t Enhanced oral bioavailability of aceclofenac has been achieved using chitosan cocrystals of aceclofenac and its entrapment into alginate matrix a super saturated drug delivery system (SDDS). Prepared SDDS were evaluated by various physiochemical and pharmacological methods. The result revealed that the primary cocrystals enhanced the solubility of the drug and the thick gelled polymer matrix that formed from swelling of calcium alginate beads makes it to release the drug in continuous and sustained manner by supersaturated drug diffusion. The C max , T max and relative bioavailability for aceclofenac cocrystal and aceclofenac SDDS were 2.06 ± 0.42 g/ml, 1 h, 159.72 ± 10.84 and 2.01 g/ml, 1 h, 352.76 ± 12.91, respectively. Anti-inflammatory activity of aceclofenac was significantly improved with the SDDS. With respect to the results, it revealed that the SDDS described herein might be a promising tool for the oral sustained release of aceclofenac and likely for that of various other poorly soluble drugs. © 2014 Elsevier B.V. All rights reserved. 1. Introduction In recent years, controlled release formulations containing aceclofenac has received much attention by the researchers in pharmaceutical industry and academic research. The most com- mercially viable formulation strategy currently employed for aceclofenac controlled release is a biphasic dosage form which consists of immediate release and a sustained release layer [1]. Vari- able gastric residence time, unpredictable gastric emptying rate and different pH of gastric region may alter the solubility, diffu- sion and absorption of the aceclofenac. Poor dissolution rate and bioavailability are the major drawbacks of orally administered ace- clofenac, these leads to severe gastric ulceration. Techniques such as solid dispersion and micro crystallization have been employed to improve its dissolution in stomach (pH 1.2) and subsequently attain a quick initial plasma concentration [2,3]. Therefore, con- trolled release of aceclofenac from its oral dosage forms in acidic pH is an important factor to maintain its narrow therapeutic window for longer duration. Recently Sougata et al. have reported a methods to deliver aceclofenac using alginate–locust bean gum based IPN ∗ Corresponding authors. Tel.: +82 41 660 1423; fax: +82 41 660 1119. E-mail addresses: chemgans@gmail.com (M. Ganesh), htjang@hanseo.ac.kr (H.T. Jang). microsphere [4], but that system only deliver the drug in intesti- nal pH (6.8) not in stomach. In the present study we attempted to produce a system that delivers the drug in acidic environment. Solid dispersions and spherical agglomerates and complexation techniques are mainly used to improve the solubility and disso- lution rate of aceclofenac [5]. Cocrystalization is one among the technique used to improve the oral solubility and dissolution rate of the drugs. In general pharmaceutical cocrystals improve the phys- ical properties such as solubility, hygroscopicity and compaction behaviors of the drug without affecting pharmacological nature of the drug [6]. For this generally synthetic organic molecules were used but they have the demerits of producing severe gastro intesti- nal (GI) irritation [7]. Cocrystals with biocompatible polymer were reported recently and evidenced their capability to improve the solubility and dissolution rate of the drug. Pharmaceutical cocrys- tals of aceclofenac dramatically improve the physical properties such as solubility, dissolution rate and pharmacokinetic proper- ties (peak plasma concentration (C max ), time to peak concentration (T max ) and bioavailability) in acidic condition are well documented. While considering the cocrystals, USFDA recommended, that the co-former used for cocrystalization should be safe to human inges- tion [8,9]. Cocrystals can induce supersaturation in the GI lumen and resulting with an improved solubility and dissolution prop- erties without being thermodynamically unstable [10]. Chitosan a well known biocompatible co-former used for the preparation of http://dx.doi.org/10.1016/j.ijbiomac.2014.12.038 0141-8130/© 2014 Elsevier B.V. All rights reserved.