Pharmaceutical nanotechnologyFloating tablets for controlled release of ofloxacin via compression coating of hydroxypropyl cellulose combined with effervescent agent
Graphical abstract
Introduction
Oral route was one of the most convenient and preferable ways for drug administration (Kagan and Hoffman, 2008), when the bioavailability of peroral drug delivery systems was determined by various factors, including the retention time of those dosage forms within the gastrointestinal tract (GIT). It has been reported that the extent of drug absorption from the GIT was related to their contact time with the small intestinal mucosa (Deshpande et al., 1996, Hirtz, 1985), while most of the conventional oral delivery systems have shown some limited bioavailability due to fast gastric-emptying time (Acharya et al., 2014). Thus, the real challenge of developing a controlled drug delivery system was not just to sustain the drug release but also to prolong the residence time of the dosage form in the stomach or the upper small intestine until all drug released at the desired rate (Zhu et al., 2014). Hence, an optimum gastro retentive dosage forms (GRDF) system could be defined as a system which would retain in the stomach for a sufficient time interval against physiological barriers with drug releasing in a controlled manner, and finally be easily metabolized in the body (Pawar et al., 2011). Currently, GRDF may be broadly classified into: high-density (sinking) systems, low-density (floating) systems, expandable systems, superporous hydrogel systems, mucoadhesive systems and magnetic systems (Bardonnet et al., 2006).
Among them, floating drug delivery system (FDDS) could basically float in the gastric fluid and prolong GRT to obtain sufficient drug bioavailability (Baumgartner et al., 2000, Sauzet et al., 2009, Singh and Kim, 2000), because of their lower bulk density compared to that of the aqueous medium. Typically, FDDS could be divided into two types: effervescent drug delivery systems which depended on the generation of carbon dioxide gas upon contact with gastric fluids and non-effervescent drug delivery systems. According to previous report, FDDS was desirable for those drugs: (i) act locally in stomach; (ii) have a narrow absorption window in the small intestinal region; (iii) are unstable in the intestinal environment and (iv) have poor solubility in a high pH environment (Bardonnet et al., 2006, El Gamal et al., 2011, Nagarwal et al., 2010, Talukder and Fassihi, 2004).
Ofloxacin is a fluoroquinolone antibacterial agent, which has a broad antimicrobial spectrum against both gram-positive and gram-negative bacteria, which has been approved for use in the treatment of gastrointestinal infections, respiratory tract infections and urinary tract infections (Zivanovic et al., 2006). Ofloxacin was readily soluble in stomach of acidic environment, but prone to precipitate in the intestine of neutral or slightly alkaline pH values, which affected their absorption in the lower section of the intestine. Apart from solubility, the absorption site is the upper part of the gastrointestinal tract (Chavanpatil et al., 2005). Therefore, various floating systems for ofloxacin have already been investigated. Chavanpatil et al. (2005) have developed ofloxacin sustained release tablet using psyllium husk, HPMC K100 M, crospovidone and sodium bicarbonate. However, when the tablets were immersed in simulated gastric fluid, the floating tablets showed burst drug release in the first 2 h. Zhang et al. (2012) reported a floating multi particulate system for ofloxacin based on a multilayer structure by coating with a release retarding film (EC), an effervescent layer (NaHCO3) and a gas-entrapped polymeric membrane (Eudragit® RL 30D), respectively. The analysis of the release mechanism showed a zero-order release for the first 8 h. However, the film coating technique is complicated and expensive (Zhang et al., 2012).
In order to overcome those drawbacks mentioned above, we combined floating drug delivery systems with controlled release systems to realize simultaneous control of drug release rate and location. Moreover, researchers found that compression-coated tablet was promising candidate to control drug release rate. A novel compression coating tablet is design to achieve zero-order release by similar release manner with the osmotic systems (Guo and Shi, 2009). Drawing on the concept, we design a novel floating drug delivery system based on the compression coating technology combined with effervescent agent.
The aim of this study were to prepare fine floating tablets via compression coating and investigate the possibility of those tablets as a delivery system for controlled release of ofloxacin. The hydrophilic polymer (hydroxypropyl cellulose) combined with effervescent agent (sodium bicarbonate) was used as the functional materials, while the sodium alginate was also utilized in the coating layer to control the drug release rate. The effects of formulation factors on the in vitro drug release behavior of those zero-order released floating tablets were studied, as well as the swelling and floating ability. Moreover, the oral bioavailability evaluation was executed in rabbits compared with market tablets TaiLiBiTuo®.
Section snippets
Materials
Ofloxacin (OFLX) was obtained from Yangtze Pharmaceutical Co., Ltd. (Taizhou, China). Three viscosity grades of hydroxypropyl cellulose (HPC) (HPC-SL: 4.0 mPa s; HPC-L: 8.0 mPa s; HPC-M: 350 mPa s) were gifted from Nippon Soda Co., Ltd. (Yokyo, Japan), and were used as a binder and hydrophilic materials to control the release rate of the compression-coated tablet. Sodium bicarbonate was obtained from Lingfeng Chemical Reagent Co., Ltd. (Shanghai, China). Magnesium stearate was obtained from Sunhere
Physicochemical characteristics of tablets
Controlled-release ofloxacin effervescent floating tablets were investigated using release-retarding gel-forming polymer like HPC and sodium alginate and a gas-forming agent like NaHCO3. In the previous work, hardness was a determining factor to the buoyancy ability of the tablets but had little effect on the drug release profile (Singh et al., 2014). Increasing the hardness would possibly lead to prolongation of the floating lag time by affecting the rate tablet penetration by the dissolution
Conclusion
In the present study, controlled-release floating tablets of ofloxacin were successfully formulated by employing NaHCO3 as a gas-forming agent, Na alginate as retarding agent and HPC as matrix. The tablets could float on the surface of artificial gastric fluid over 12 h and control the drug release for 12 h. Furthermore, the controlled-release floating tablets could improve the bioavailability without increasing the fluctuation of plasma concentrations. In summary, the controlled-release floating
Acknowledgments
This work was financially supported by the Fundamental Research Funds for the Central Universities (Program Nos. 2015ZD007, 2015PT052), the National Natural Science Foundation of China (No. 81402859) and the Natural Science Foundation of Jiangsu Province (No. BK20130663).
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These authors contributed equally to this work.