Studying the Release Profile of 5-Fluorouracil Prepared By Controlled Porosity Osmotic System As A Colon Targeting
DOI:
https://doi.org/10.59480/phahs.v1i2.23Keywords:
Controlled Porosity Osmotic System (CPOP-CT), Osmotic Pressure, low molecular weight chitosan (LMCh), medium molecular weight chitosan (MMCh), semipermeable cellulose acetate membrane (CAM), Enzyme, 5-FUAbstract
In this study, different formulas (F1-F7) containing 4 mg of 5-fluorouracil (5-FU) were prepared as a tablet in form of CPOP-CT. The core of these formulas contained citric acid, sodium chloride, LMCh, MMCh, ProSolv SMCC®90 and magnesium stearate mixed with 5-FU. The formulas were double coated by an inner layer containing chitosan and PEG-400 and outer layer as an enteric coating containing Eudragit®L100-55, triethyl citrate and talc. The solubility of 5-FU in different dissolution media (pH 5, pH 7) was studied. The results indicated increase of LMCh and decrease of citric acid lead to slow the release of 5-FU for F1, F2, F3, F4, F5, F6 and F7 in simulated colonic fluid with 61%, 29%, 32%, 43%, 52%, 39% and 68%, respectively within 21 h. In addition, the release rate of 5-FU was affected by changing the weight gain percentages of semipermeable CAM. 6% and 10% weight gains of F3 released 5-FU completely within times (t100% ) of 46 h and 65 h, respectively which are acceptable with colonic transit time (78 h) compared with 14% weight gain (t100% = 135 h). In SCF, the enzymatic effect on the release of 5-FU within 21 h for F6 was studied which synthetic almond emulsin β-glucosidase and human fecal enzyme increased release of 5-FU with 26% and 39%, respectively compared to 18% release with no enzyme. Degradation effect of these enzymes made pores in semipermeable to release drugs and then modulate the drug kinetic from zero order into first order.
References
Leopold CS. Coated dosage forms for colon-specific drug delivery. Pharm Sci Tech Tod 1999; 2(5): 197-204.
Liu H, X Yang G, Nie SF, Zhou LL, Liu H, Tang R, Pan WS, Chitosan-based controlled porosity osmotic pump for colon-specific delivery system: Screening of formulation variables and in vitro investigation. Int J Pharm 2006; 24 Sep: 1-10.
Zhang H and Neau SH. In vitro degradation of chitosan by bacterial enzymes from rat cecal and colonic contents. Biomaterials 2002; 23(13): 2761-2766.
Chourasia, MK, Jain SK, Pharmaceutical approaches to colon targeted drug delivery systems, J Pharm Pharmaceut Sci 2003; 6(1): 33-66.
Kelm GR, Kondo K, Nakajima A. Pharmaceutical dosage form with multiple enteric polymer coatings for colonic delivery. US Patent 5914132 1999; 22: 1-18.
Santus G, Baker RW. Osmotic drug delivery: A review of the patent literature. J Control Release 1995; 35: 1–21.
Liu L, Khang G, Rhee JM, Lee HB. Monolithic osmotic tablet system for nifedipine delivery. J Control Release 2000; 67: 309–322.
Lamprecht A, Yamamoto H, Takeuchi H, Kawashima Y. Microsphere design for the colonic delivery of 5-fluorouracil. J Control Rel 2003; 90: 313–322.
Duschinsky R, Pleven A, Heidelberger C. The Synthesis of 5-Fluoro- Pyrimidines. J Am Chem Soc 1957; 79: 4559-4560.
Heidelberger C. In: Antineoplastic and Immunosuppressive Agents. Sartorelli AC, John DG, eds. Part 11, Springer, Berlin, Heidelberger, New York 1975: 193-231.
Malet MM, Martino R. Clinical studies of three oral prodrugs of 5-fluorouracil (capecitabine, UFT, S-1): A review. Oncologist 2002; 7(4): 288-323.
Mandel HG. The incorporation of 5-fluorouracil into RNA and its molecular consequences. Prog Mol Subcell Biol 1969; 1: 82-135.
Nei S, Fan X, Peng Y, Yang X, Wang C, Pan S. In vitro and in vivo studies on the complexes of vinpocetine with hydroxypropyl-β-cyclodextrin. Arch Pharm Res 2007; 30(8): 991-1001.
US Pharmacopeia XXIII. Buffer Solution. US Pharmacopeial Convention. Rockville MD 1995: 2053.
Kohler F. Buffer solutions. In: Scientific Tables. Lentner C ed. Geigy. Basle, Ciba-Geigy Ltd 1984: 58–60.
Singh BN. Modified-Release Solid Formulations for Colonic Delivery. Recent Patents on Drug Delivery Formulation 2007; 1: 53-63.
Sekigawa F, Onda Y. Coated solid medicament from having releasability in large intestine. US patent 5217720 1993; 8: 1-10.
Cappuccino JG, Sherman N. Techniques for the Cultivation of Anaerobic Microorganisms. In: Microbiology a Labrotary Manual, 8th. San Francisco, USA 2008: 127-128.
US Pharmacopeia XXIII. 711 Dissolution. US Pharmacopeial Convention. Rockville MD 1995: 1578-1579.
Kanagale P, Lohray BB, Misra A, Davadra P, Kini R. Formulation and Optimization of Porous Osmotic Pump–based Controlled Release System of Oxybutynin, AAPS Pharm Sci Tech 2007; 8(3): E1-E7.
Kristl J, Smid- Korbar J, Struc E, Schara M, Rupprecht H. Hydrocolloids and gels of chitosan as drug carriers. Int J Pharm 1993; 99: 13- 19.
Nangia A, Li B, Dely A, Lodin U, Cardinal JR. Controlled release composition with semi-permeable membrane and poloxamer flux enhancer. US Patent 0048119 2005; 3: 1-7.
Nakatsuka SH. Cellulose acetate semipermeable membrane and process for producing the cellulose acetate semipermeable membrane. US Patent 6372136 B1 2002; 16: 1-12.
Petereit HU, Weisbrod W. Formulation and process considerations affecting the stability of solid dosage forms formulated with methacrylate copolymers. Euro J Pharma Biopharm 1999; 47: 15-25.
Säkkinen M. Ph.D. Thesis .Biopharmaceutical Evaluation of Microcrystalline Chitosan as Release- Rate- Controlling Hydrophilic Polymer in Granules for Gastro- Retentive Drug Delivery. Department of Pharmacy. Division of Biopharmaceutics and Pharmacokinetics, University of Helsinki 2003: 1-63.
Nykänan P. Ph.D. Thesis. Development of Multiple-Unit Oral Formulations for Colon-Specific drug Delivery Using Enteric Polymers and Organic Acids as Excipients, Department of Pharmacy. Division of Biopharmaceutics and Pharmacokinetics, University of Helsinki 2003: 1-55.
Anagale P, Lohray BB, Misra A, Davadra P, and Kini R. Formulation and Optimization of Porous Osmotic Pump–based Controlled Release System of Oxybutynin, AAPS Pharm Sci Tech 2007; 8(3): 1-7.
Säkkinen M, Tuononen T, Jürjenson H, Veski P, Marvola M Evaluation of microcrystalline chitosan for gastro- retentive drug delivery. Eur J Pharm Sci 2003: 19: 345-353.
McClelland GA, Sutton SC, Engle K, Zentner GM. The solubility-modulated osmotic pump: In vitro/in vivo release of diltiazem hydrochloride. Pharm Res 1991; 8: 88–92.
Verma RK, Mishra B, Garg S. Osmotically controlled oral drug delivery. Drug Dev Ind Pharm 2000; 26: 695–708.
Jensen JL, Appel LE, Clair JH, Zentner GM. Variables that affect the mechanism of drug release from osmotic pumps coated with acrylate/methacrylate copolymer latexes. J Pharm Sci 1995; 84: 530–533.
Ozturk AG, Ozturk SS, Palsson BO, Wheatley TA, Dressman JB. Mechanism of release from pellets coated with an ethylcellulose-based film. J Control Rel 1990; 14: 203–213.
McClelland GA, Sutton SC, Engle K, Zentner GM. The solubility-modulated osmotic pump: In vitro/in vivo release of diltiazem hydrochloride. Pharm Res 1991; 8: 88–92.
Theeuwes F. Elementary osmotic pump. J Pharm Sci 1975; 64: 1987–1991.
Wu PC, Tsai MJ, Huang YB, Chang JS, Tsai YH. In vitro and in vivo evaluation of potassium chloride sustained release formulation prepared with saturated polyglycolyed glycerides matrices. Int J Pharm 2002; 243: 119-124.
Verma RK, Garg S. Development and evaluation of osmotically controlled oral drug delivery system of glipizide. Eur J Pharm Biopharm 2004; 57: 513-525.
Nunthanid J, Huanbutta K, Luangtana-anan M, Sriamornsak P, Limmatvapirat S, Puttipipatkhachorn S. Development of time-, pH-, and enzyme-controlled colonic drug delivery using spray-dried chitosan acetate and hydroxypropyl methylcellulose. Eur J Pharm Biopharm 2007; 31(5): 1-7.
Zambito Y, Di Colo G. Preparation and in vitro evaluation of chitosan matrices for colonic controlled drug delivery. J Pharm Pharmaceut Sci 2003; 6(2): 274- 281.
Cummings JH, Macfarlane GT. The Colonic Flora, Fermentation and Large Bowel Digestive Function. In: The large intestine: Physiology, Pathophysiology and Disease. Philips SF, Pemberton JH, Shorter RG eds. Raven press Ltd., New York 1991: 51-92.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2023 Muath Mohammed Ameen, Alaa A. Abdul Rasool
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
All PHAHS Journal articles are published under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND 4.0) which allows authors retain copyright and others may not use the material for commercial purposes. A commercial use is one primarily intended for commercial advantage or monetary compensation. If others remix, transform, or build upon the material, they may not distribute the modified material.
Copyright on any research article published by the PHAHS Open Access journal is retained by the author(s). Authors also grant any third party the right to use the article freely as long as its original authors, citation details and publisher are identified.
Use of the article in whole or part in any medium requires attribution suitable in form and content as follows: [Title of Article/Author/Journal Title and Volume/Issue. Copyright (c) [year] [copyright owner as specified in the Journal]. Links to the final article on PHAHS website are encouraged where applicable.
The CC BY-NC-ND 4.0 Creative Commons Attribution License does not affect the moral rights of authors, including without limitation the right not to have their work subjected to derogatory treatment. It also does not affect any other rights held by authors or third parties in the article, including trademark or patent rights, or the rights of privacy and publicity. Use of the article must not assert or imply, whether implicitly or explicitly, any connection with, endorsement or sponsorship of such use by the author, publisher or any other party associated with the article.
Pharmacy and Applied Health Science: A Scientific Periodical Open Access Journal and has no APC & ASC.