International Journal of Pharmaceutics 236 (2002) 43 – 55 Studies on the development of oral colon targeted drug delivery systems for metronidazole in the treatment of amoebiasis Y.S.R. Krishnaiah *, P.R. Bhaskar Reddy, V. Satyanarayana, R.S. Karthikeyan Department of Pharmaceutical Sciences, Andhra Uniersity, Visakhapatnam 530 003, India Received 1 October 2001; received in revised form 21 December 2001; accepted 25 December 2001 Abstract The aim of the present study is to develop colon targeted drug delivery sytems for metronidazole using guar gum as a carrier. Matrix, multilayer and compression coated tablets of metronidazole containing various proportions of guar gum were prepared. All the formulations were evaluated for the hardness, drug content uniformity, and were subjected to in vitro drug release studies. The amount of metronidazole released from tablets at different time intervals was estimated by high performance liquid chromatography method. Matrix tablets and multilayer tablets of metronidazole released 43 – 52% and 25 – 44% of the metronidazole, respectively, in the physiological environment of stomach and small intestine depending on the proportion of guar gum used in the formulation. Both the formulations failed to control the drug release within 5 h of the disolution study in the physiological environment of stomach and small intestine. The compression coated formulations released less than 1% of metronidazole in the physiological environment of stomach and small intestine. When the dissolution study was continued in simulated colonic fluids, the compression coated tablet with 275 mg of guar gum coat released another 61% of metronidazole after degradation by colonic bacteria at the end of 24 h of the dissolution study. The compression coated tablets with 350 and 435 mg of guar gum coat released about 45 and 20% of metronidazole, respectively, in simulated colonic fluids indicating the susceptibility of the guar gum formulations to the rat caecal contents. The results of the study show that compression coated metronidazole tablets with either 275 or 350 mg of guar gum coat is most likely to provide targeting of metronidazole for local action in the colon owing to its minimal release of the drug in the first 5 h. The metronidazole compression coated tablets showed no change either in physical appearance, drug content or in dissolution pattern after storage at 40 °C/75% RH for 6 months. © 2002 Elsevier Science B.V. All rights reserved. Keywords: Guar gum; Metronidazole; Colon targeting; In vitro dissolution; Compression coating www.elsevier.com/locate/ijpharm 1. Introduction Amoebiasis is an infection of the large intestine caused by Entamoeba histolytica, a single celled * Corresponding author. Tel.: +91-891-530272; fax: +91- 891-747969/755547. E-mail address: krishnaysr112@rediffmail.com (Y.S.R. Kr- ishnaiah). 0378-5173/02/$ - see front matter © 2002 Elsevier Science B.V. All rights reserved. PII:S0378-5173(02)00006-6