Formulation and evaluation of mastic gum as a compression coat for colonic delivery of 5-flurouracil
Keywords:
Mastic gum, 5-flurouracil,, Compression coating, Colonic deliveryAbstract
Mastic gum has been reported to possess considerable anti-tumor activity against human colorectal cancer. The purpose of this work was to evaluate mastic gum in formulation of colon-specific 5-flurouracil delivery system for effective treatment of colorectal cancer. Compression coated tablets, containing 5-flurouracil in the core tablet coated with 200 mg of different coating materials containing various proportions of mastic gum were evaluated for their 5-flurouracil in vitro release. The results indicated that the concentrations of mastic gum, sodium chloride as well as hydroxypropyl methyl cellulose (HPMC) in the coating materials significantly modify the drug release. The coating material (F6) consisted of 60% mastic gum, 15% sodium chloride and 25% HPMC is considered as a promising formula for achieving colon targeting of 5-flurouracil. Further, gamma-scintigraphic studies were carried out in healthy male volunteers to evaluate in vivo release of F6. The results showed that tablets remained intact in stomach and small intestine, however partial and complete release of the tracer occurred in the colon. The in-vitro antitumor activity of 5-flurouracil-mastic gum combination mixed in a ratio representing their concentrations in tablets coated with F6 was carried out against colon cancer cell line using MTT assay. The results revealed that 5-flurouracil-mastic gum mixture was more effective in arresting cell growth in comparison to that shown by 5-flurouracil or mastic alone. In conclusion, this new colonic drug delivery system is potentially useful for 5-flurouracil colon targeting. However, clinical benefits of using mastic in formulation of 5-flurouracil colonic tablets need further evaluation.
References
Ricchi P, Zarrilli R, Di Palma A, Acquaviva AM. Nonsteroidal anti inflammatory drugs in colorectal cancer: from prevention to therapy. Br J Cancer 2003; 88:803–807.
Michor F, Iwasa Y, Lengauer C, Nowak MA. Dynamics of colorectal cancer. Semin Cancer Biol 2005; 15 (6):484-493.
Krishnaiah YSR, Satyanarayan S. Colon-specific drug delivery systems. In: Jain NK, ed. Advances in Controlled and Novel Drug Delivery. New Delhi, India: CBS Publishers and Distributors. 2001: pp 89 -119.
Chourasia MK, Jain SK. Pharmaceutical approaches to colon targeted drug delivery systems. J Pharm Pharm Sci 2003; 6 (1):33-66.
Basit AW. 2005. Advances in colonic drug delivery. Drugs 65(14):1991–2007.
Jain A, Gupta Y, Jain SK. Azo-chemistry and its potential for colonic delivery. Crit Rev Ther Drug Carrier Syst 2006; 25:349– 400.
Martindale-The Extra Pharmacopoeia, 28th edition. London, UK. The Pharmaceutical Press, 1982; p 315.
Al-Said MS, Ageel AM, Parmar NS, Tariq M. Evaluation of mastic, a crude drug obtained from Pistacia lentiscus for gastric and duodenal anti-ulcer activity. J Ethnopharmacol 1986; 15:271-278.
Al-Habbal MJ, Al-Habbal Z, Huwez FU. A double-blind controlled clinical trial of mastic and placebo in the treatment of duodenal ulcer. Clin Exp Pharmacol Physiol 1984; 5:541-544.
Huwez FU, Al-Habbal MJ. Mastic in treatment of benign gastric ulcers. Gastroenterol Jpn 1986; 3:273-274.
Dimas K, Hatziantoniou S, Wyche JH, Pantazis P. A mastic gum extract induces suppression of growth of human colorectal tumor xenografts in immunodeficient mice. In Vivo 2009; 23(1):63- 68.
Balan KV, Prince J, Han Z, Dimas K, Cladaras M, Wyche JH, Sitaras NM, Pantazis P. Antiproliferative activity and induction of apoptosis in human colon cancer cells treated in vitro with constituents of a product derived from Pistacia lentiscus L. var. chia. Phytomedicine 2007; 14(4):263-272.
Liu J. Oleanolic acid and ursolic acid: research perspectives. J Ethnopharmacol 2005; 100: 92-94.
Panagopoulou A, Georgarakis M. Effect of compression and diluent on drug release from mastic matrix tablets. A statistical analysis. Drug Dev Ind Pharm1990; 16:637-646.
Abdel-Aleem HM. Formulation and evaluation of mastic in antacid preparations. Alex J Phar Sci 1996; 10:65-68.
Georgarakis M, Groning R, Henzler P. Microencapsulation of potassium chloride with mastic. Pharmazie 1987; 42:455-456.
Assimopoulou AN, Papageorgiou VP, Kiparissides C. Synthesis and release studies of shikonin containing microcapsules prepared by the solvent evaporation method. J Microencapsul 2003; 20:581-596.
Assimopoulou AN, Papageorgiou VP. Preparation and release studies of alkannin containing microcapsules. J Microencapsul 2004; 21:161-173.
Micoli G, Turci R, Arpellini M, Minoia C. Determination of 5-flurouracil in environmental samples by solid-phase extraction and high-performance liquid chromatography with ultraviolet detection. J Chromatogr B Biomed Sci Appl 2001; 750: 25–32.
Yassin AE, Alsarra IA, Alanazi FK, Al-Mohizea AM, Al-Robayan AA, Al-Obeed OA. New targeted-colon delivery system: in vitro and in vivo evaluation using X-ray imaging. J Drug Target 2010; 18(1):59-66.
Chaurasia M, Chourasia MK, Jain NK, Jain A, Soni V, Gupta Y, Jain SK. Cross-Linked Guar Gum Microspheres: A Viable Approach for Improved Delivery of Anticancer Drugs for the Treatment of Colorectal Cancer. AAPS PharmSciTech 2006; 7 (3), article 74, E143-E151.
Krishnaiah YS, Satyanarayana V, Dinesh Kumar B, Karthikyan RS. In vitro drug release studies on guar gum-based colon targeted oral drug delivery systems of 5-flurouracil. Eur J Pharm Sci 2002; 16:185–192.
Lamprecht A, Yamamoto H, Takeuchi H, Kawashima Y. Microsphere design for the colonic delivery of 5-flurouracil. J Control Release 2003; 90:313–322.
Zhang G, Liu T, Chen YH, Chen Y, Xu M, Peng J, Yu S, Yuan J, Zhang X. Tissue specific cytotoxicity of colon cancer cells mediated by nanoparticle-delivered suicide gene in vitro and in vivo. Clin Cancer Res 2009; 15(1):201-207.
Zambito Y, Baggiani A, Carelli V, Serafín MF, Di Colo G. Matrices for site-specific controlled-delivery of 5-flurouracil to descending colon. J Control Release 2005; 102:669- 677.
Ramani CC, Puranik PK, Dorle AK. Study of diabietic acid as matrix forming material. Int J Pharm 1996; 137: 11-19.
World Health Organization. Quality control methods for medicinal plant materials. Geneva: World Health Organization 1998.
Costa P, Sousa JM. Modeling and comparison of dissolution profiles. Eur J Pharm Sci 2001; 13(2):123–133.
Pillay V, Fassihi R. Evaluation and comparison of dissolution data derived from different modified release dosage forms: an alternative method. J Control Release 1998; 55:45–55.
Korsemeyer RW, Gurny R, Doelker E, Buri P, Peppas NA. Mechanisms of solute release from porous hydrophilic polymers. Int J Pharm 1983; 15:25-35.
Siepmann J, Peppas NA. Modeling of drug release from delivery systems based on hydroxypropyl methylcellulose (HPMC). Adv Drug Deliv Rev 2001; 48:139–157.
Peppas NA. Analysis of Fickian and non-Fickian drug release from polymers. Pharm Acta Helv 1985; 60:110–111.
Krishnaiah YSR, Satyanarayana S, Rama Prasad YV, Narasimha Rao S. Evaluation of guar gum as a compression coat for drug targeting to colon. Int J Pharm 1998; 171: 137–146.
Sinha VR, Mittal BR, Rachna K. In vivo evaluation of time and site of disintegration of polysaccharide tablet prepared for colon-specific drug delivery. Int J Pharm 2005; 289: 79–85.
Kwabena OK, John TF, Harbans LS, Anne-Marie S. Gamma scintigraphic evaluation of film-coated tablets intended for colonic or biphasic release. Int J Pharm 2004; 270: 307–313.
United States Pharmacopoeia-XXIII, National Formulary-XVIII, United States Pharmacopeial Convention Inc. Rockville, MD. 1995; pp 1625–1626.
Kuksal A, Tiwary AK, Jain NK, Jain S. Formulation and In Vitro-In Vivo evaluation of extended-release matrix tablets of Zidovudine: Influence of combination of hydrophilic and hydrophobic matrix formers. AAPS Pharm Sci Tech 2006; 7(1), article 1, E1-E9.
González-Rodríguez ML, Pérez-Martínez JI, Merino S, Fini A, Rabasco AM. Channeling Agent and Drug Release from a Central Core Matrix Tablet. Drug Dev Ind Pharm 2001; 27(5): 439–446.
Dahl TC, Calderwood T, Bormeth A, Trimble K, Piepmeier E. Influence of Physico-chemical properties of hydroxypropyl methylcellulose on naproxen release from sustained release matrix tablets. J Control Release 1990; 14: 1–10.
Li CL, Martini LG, Ford JL, Roberts M. The use of hypromellose in oral drug delivery. J Pharm Pharmacol 2005; 57: 533–546.
Landgraf W, Nai-Hong L, James RB. Polymer microcarrier exhibiting zero-order release. Drug Delivery Technology 2003 ; Vol 3, No.1
Mosmann T. Rapid colorimetric assays for cellular growth and survival: Application to proliferation and cytotoxicity assays. J Immunol Methods 1983; 65:55-63.
