FACTORS INFLUENCING DELAYED RELEASE FOLLOWED BY RAPID PULSE RELEASE OF DRUGS FROM COMPRESSION COATED TABLETS FOR COLON TARGETING Original Article AMRITA CHAKRAVORTY a , MAINAK CHAKRABORTY b , BISWANATH SA a* a Division of Pharmaceutics, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032, India, b Division of Pharmacology, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032, India. Email: biswanathsa2003@yahoo.com Received: 13 May 2016 Revised and Accepted: 20 Jun 2016 ABSTRACT Objective: This work was undertaken to develop colon targeted tablets that can minimize premature release of ibuprofen (IBP) and metronidazole (MNZ) in a lag period of 7h during which the tablets are likely to remain in the upper gastro-intestinal tract, and produce rapid pulse release within 1-5 h after the lag period when the tablets could be located in the colon with or without intervention of colonic microflora. Methods: Core tablets of ibuprofen and metronidazole containing different amounts of tri-sodium citrate (TSC) as osmogen were compression coated with locust bean gum (LBG) and carboxymethyl LBG (CMLBG). In vitro drug release studies were performed in a dynamic pH shift condition with or without rat cecal matters. The release of the drugs were also monitored at different hydrodynamic conditions. Results: In vitro release studies revealed that increase in the amount of TSC, decrease in coat-weight and change in hydrodynamic conditions influenced the drug release considerably. While LBG coated tablets under the stated conditions failed to provide complete release of the drugs in 12 h, CMLBG coated tablets produced complete release rapidly in the post lag period minimizing the release in the initial 7 h. Presence of rat cecal matter in dissolution medium further accentuated the release of the drugs from CMLBG compression coated tablets in the post lag period. Conclusion: The study revealed that tablets containing appropriate amount of osmogen in the core and compression coated with suitable amount of CMLBG may be suitable for colon targeting of drugs even in the absence of colonic microflora. Keywords: LBG, CMLBG, Osmogen, Rat cecal content, In vitro dissolution © 2016 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/) INTRODUCTION Development of colon-targeted drug delivery systems intended for administration through oral route has become the most challenging task to the pharmaceutical researchers because of the possibility of premature drug release in the upper gastrointestinal tract (g.i.t.) before reaching the colon. Colon specific dosage forms are of immense importance for the treatment of colon-related diseases such as Crohn’s disease, ulcerative colitis, inflammatory bowel syndrome and colorectal cancer [1], as they provide high local drug concentration at the afflicted site of colon, and thereby, produce optimum therapeutic response and reduce the emergence of adverse drug-effects associated with premature drug release and subsequent absorption through the upper g.i.t. [2-5]. As the gastric residence time of tablets ranges from 0.5 h to about 2 h and small intestinal transit time of about 3 h is fairly constant [6], the time required for a tablet dosage form to reach colon may be considered as 5 h. Adding a buffer time of 2 h due to further variation in transit time if any, the strategy for designing a colon-targeted dosage form should be to prevent or minimize premature drug release (below 10 %) for a period of 7 h (lag period) following which the drug should be released rapidly and completely within 7-12 h (post lag time) to provide high local concentration of drug in colon. Various methods such as coating with pH-sensitive polymers, time- dependant release systems, compression coating with bio- degradable polysaccharides have been developed for achieving colon targeting of drugs [7]. Principally these dosage forms consist of a reservoir system in which an immediate release core is covered with a suitable barrier coating to protect the drug release in lag period. The barrier may be a pH-sensitive polymer such as methacrylic acid and methylmethacrylate copolymers [8] or a polysaccharide degradable by colonic microflora [9,10]. The rationale of compression coating of tablets with polysaccharides for colon targeting of drugs is that large number of anaerobic bacteria present in the human colon secrete various enzymes to degrade polysaccharides which are not digested in the upper g.i.t. [11]. Although the composition of human gut ecosystem may be altered by various factors [12], microbially triggered systems which are based on compression coating of an immediate release tablet with a biodegradable polysaccharide have been investigated extensively [13-17]. However, available literatures indicate that after a satisfactory lag period, the drugs from compression coated tablets are released in the colon in a sustained release manner rather than in a rapid pulse release fashion [13-16]. Osmotic pressure controlled drug delivery systems with several modifications have been developed. When a tablet consisting of a core of an osmotically active drug, or a core of osmotically inactive drug in combination with an osmotically active salt and surrounded by a semi permeable membrane is brought into contact with water, the release of the drug takes place through an orifice at a constant rate due to osmotic pressure difference. In the absence of orifice, imbibed water develops hydraulic pressure inside the tablet until the core ruptures and the contents are released [18]. It is therefore possible that presence of an osmotically active salt (osmogen) in the core of a compression coated tablet may induce complete release of the drug rapidly in the post lag period. In addition, variable environment of human gut system in colon-related diseases may alter the hydrodynamic condition and subsequently, affect the drug release behavior from compression coated tablets in both lag and post lag time periods. The objective of the present work was to develop locust bean gum (LBG) and carboxymethyl locust bean gum (CMLBG) compression coated tablets of ibuprofen (IBP) and metronidazole (MNZ) containing different amounts of osmogen in the core and polysaccharides in the coat, and to evaluate the effect of osmogen, coat weight and hydrodynamic condition on in vitro release behavior of drugs during the lag and post lag periods. The effect of microbial flora on the drug release in the post lag period was examined using rat cecal matter in dissolution medium. LBG and CMLBG were selected as polysaccharides for compression coating as LBG is susceptible to International Journal of Pharmacy and Pharmaceutical Sciences ISSN- 0975-1491 Vol 8, Issue 8, 2016