Formulation and evaluation of colon targeted drug delivery system

The main objective of the present study was to develop colon targeted drug delivery systems for Nitrofurantoin using guar gum as a carrier. Matrix tablets containing various proportions of guar gum were prepared by wet granulation technique using starch paste as a binder. The in-vitro drug release study was undertaken at 37±0.5°C in 0.1N Hcl for 2 hr; followed by pH 7.4 phosphate buffer (3hr) finally in simulated colonic fluid pH 6.8 phosphate buffer containing 4% w/v rat ceacal content for 10 hr. It was found that 10.04% drug is released in first 5hr from F4 (GG-20%), where as the other matrix tablets released 20-30% of Nitrofurantoin in physiological environment of stomach and small intestine. When studies were continued in colonic fluids, matrix tablets released almost 100% drug. The results of the study show that matrix tablets containing 20% of guar gum are most likely to provide targeting of Nitrofurantoin in the colon. Key-Words: Colon targeted drug delivery, Nitrofurantoin, In-Vitro dissolution, Guar gum, Rat caecal content Introduction The oral route of drug administration is the most convenient and important method of administering drugs for systemic effect. Nearly 50% of the drug delivery systems available in the market are oral D.D.S. and these systems have more advantages due to patient acceptance and ease of administration [1, 2] . During the last decade there has been interest in developing site-specific formulations for targeting drug to the colon. Colonic drug delivery has gained increased importance not just for the delivery of the drugs for the treatment of local diseases associated with the colon like Crohn’s disease, ulcerative colitis, irritable bowel syndrome and constipation but also for the systemic delivery of proteins, therapeutic peptides, antiasthmatic drugs, antihypertensive drugs and antidiabetic agents [3, 4] . There are various methods or techniques through which colon drug targeting can be achieved, for example, formation of prodrug, coating with pH-sensitive polymers, coating with biodegradable polymers, designing formulations using polysaccharides, timed released systems, pressurecontrolled drug delivery systems, osmotic pressure controlled systems [5, 6] . Coating of the drugs with pHsensitive polymers provides simple approach for colonspecific drug delivery. * Corresponding Author E .Mail: [email protected] Material and Methods Materials Nitrofurantoin was a gift sample from Taj Pharmaceuticals Ltd., Mumbai. Guar gum, lactose, starch, talc, magnesium stearate, other chemicals and the solvents used were of analytical grade Preparation of Nitrofurantoin matrix tablets Matrix tablets of Nitrofurantoin were prepared by wet granulation method. Lactose was used as diluent and a mixture of talc–magnesium stearate (1:1) was used as lubricant. Guar gum was included in the formulations in various proportions. The compositions of different formulations used in the study containing 50 mg of Nitrofurantoin in each case are shown in Table 1. In all the formulations, guar gum was sieved (<250 μm) separately and mixed with Nitrofurantoin (<150 μm) and MCC (<250 μm). The powders were blended and granulated with 12% starch paste. The wet mass was passed through a mesh (1680 μm) and the granules were dried at 60 C for 2 hr. The dried granules were passed through a mesh (1190 μm) and these granules were lubricated with a mixture of talc–magnesium stearate (1:1). The lubricated granules were compressed at a compression force of 4000–4500 kg using 9 mm round, flat and plain punches on a single station tabletting machine (M / s Cadmach Machinery, India). Research Article [Singh, 3(12 Suppl.): Dec., 2012] CODEN (USA): IJPLCP ISSN: 0976-7126 Int. J. of Pharm. & Life Sci. (IJPLS), Vol. 3, Issue 12(Suppl.): December: 2012, 2265-2268 2266 Table 1: Composition of Nitrofurantoin matrix tablets containing 5% (F1), 10% (10%), 15% (F3) and 20% (F4) of guar gum Ingredients Quantity (mg) present per each matrix tablet