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Novel microbially triggered colon specific delivery system of 5-Fluorouracil: statistical optimization, in vitro, in vivo, cytotoxic and stability assessment.
Int J Pharm. 2011 Jun 15; 411(1-2):142-51.IJ

Abstract

The present study aimed to statistically optimize a colon specific formulation of 5-Fluorouracil for the treatment of colon cancer. A 3(2) full factorial design was used for optimization. The independent variables employed were amount of pectin and amount of starch paste, each at three levels. The evaluated responses were hardness, percent cumulative drug release (% CDR) at 5th h and t(90%) (time required for 90% of drug release). Drug release studies were carried out using change over media [pH 1.2, 7.4 and 6.5 in presence of 4% (w/v) rat caecal contents]. The optimized formulation was subjected to in vivo roentgenographic studies in New Zealand white rabbits to analyze the in vivo behaviour of the developed tablets. This formulation was also evaluated for cytotoxic potential using HT-29 human colon cancer cell lines. Pharmacokinetic studies in New Zealand white rabbits were conducted to determine the extent of systemic exposure provided by the developed formulation in comparison to an immediate release tablet. The optimized formulation consisting of pectin (66.67%, w/w) and starch paste (15%, w/w) released negligible amount of drug at pH 1.2 and pH 7.4 whereas significant (p < 0.05) drug release was observed at pH 6.5 in presence of 4% (w/v) rat caecal contents. Roentgenographic studies corroborated the in vitro observations, thus providing the "proof of concept". Pharmacokinetic studies revealed significant reduction in systemic exposure and cytotoxicity studies demonstrated enhanced cellular uptake of drug by the developed formulation. Shelf life of the formulation was found to be 2.83 years. The results of the study established pectin-based coated matrix tablet to be a promising system for the colon specific delivery of 5-FU so as to treat colon carcinoma.

Authors+Show Affiliations

Department of Pharmaceutics, Rajiv Academy for Pharmacy, Mathura 281001, UP, India.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

21463667

Citation

Dev, Rakesh Kumar, et al. "Novel Microbially Triggered Colon Specific Delivery System of 5-Fluorouracil: Statistical Optimization, in Vitro, in Vivo, Cytotoxic and Stability Assessment." International Journal of Pharmaceutics, vol. 411, no. 1-2, 2011, pp. 142-51.
Dev RK, Bali V, Pathak K. Novel microbially triggered colon specific delivery system of 5-Fluorouracil: statistical optimization, in vitro, in vivo, cytotoxic and stability assessment. Int J Pharm. 2011;411(1-2):142-51.
Dev, R. K., Bali, V., & Pathak, K. (2011). Novel microbially triggered colon specific delivery system of 5-Fluorouracil: statistical optimization, in vitro, in vivo, cytotoxic and stability assessment. International Journal of Pharmaceutics, 411(1-2), 142-51. https://doi.org/10.1016/j.ijpharm.2011.03.057
Dev RK, Bali V, Pathak K. Novel Microbially Triggered Colon Specific Delivery System of 5-Fluorouracil: Statistical Optimization, in Vitro, in Vivo, Cytotoxic and Stability Assessment. Int J Pharm. 2011 Jun 15;411(1-2):142-51. PubMed PMID: 21463667.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Novel microbially triggered colon specific delivery system of 5-Fluorouracil: statistical optimization, in vitro, in vivo, cytotoxic and stability assessment. AU - Dev,Rakesh Kumar, AU - Bali,Vikas, AU - Pathak,Kamla, Y1 - 2011/04/02/ PY - 2011/01/28/received PY - 2011/03/23/revised PY - 2011/03/27/accepted PY - 2011/4/6/entrez PY - 2011/4/6/pubmed PY - 2012/1/11/medline SP - 142 EP - 51 JF - International journal of pharmaceutics JO - Int J Pharm VL - 411 IS - 1-2 N2 - The present study aimed to statistically optimize a colon specific formulation of 5-Fluorouracil for the treatment of colon cancer. A 3(2) full factorial design was used for optimization. The independent variables employed were amount of pectin and amount of starch paste, each at three levels. The evaluated responses were hardness, percent cumulative drug release (% CDR) at 5th h and t(90%) (time required for 90% of drug release). Drug release studies were carried out using change over media [pH 1.2, 7.4 and 6.5 in presence of 4% (w/v) rat caecal contents]. The optimized formulation was subjected to in vivo roentgenographic studies in New Zealand white rabbits to analyze the in vivo behaviour of the developed tablets. This formulation was also evaluated for cytotoxic potential using HT-29 human colon cancer cell lines. Pharmacokinetic studies in New Zealand white rabbits were conducted to determine the extent of systemic exposure provided by the developed formulation in comparison to an immediate release tablet. The optimized formulation consisting of pectin (66.67%, w/w) and starch paste (15%, w/w) released negligible amount of drug at pH 1.2 and pH 7.4 whereas significant (p < 0.05) drug release was observed at pH 6.5 in presence of 4% (w/v) rat caecal contents. Roentgenographic studies corroborated the in vitro observations, thus providing the "proof of concept". Pharmacokinetic studies revealed significant reduction in systemic exposure and cytotoxicity studies demonstrated enhanced cellular uptake of drug by the developed formulation. Shelf life of the formulation was found to be 2.83 years. The results of the study established pectin-based coated matrix tablet to be a promising system for the colon specific delivery of 5-FU so as to treat colon carcinoma. SN - 1873-3476 UR - https://www.unboundmedicine.com/medline/citation/21463667/Novel_microbially_triggered_colon_specific_delivery_system_of_5_Fluorouracil:_statistical_optimization_in_vitro_in_vivo_cytotoxic_and_stability_assessment_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-5173(11)00293-6 DB - PRIME DP - Unbound Medicine ER -