International Journal of Drug Delivery Technology
Volume 14, Issue 3

Development and Analysis of Colon-Specific, pH-Responsive Polymer Delivery of Irinotecan Hydrochloride Tablets for Colon Cancer Treatment

Mahalekshmi V1,, Balakrishnan N2, Ajay Kumar T.V3 and Parthasarathy V4*

1Research Scholar, Department of Pharmacy, Annamalai University, Annamalai Nagar, Tamil Nadu, India.

2S.A. Raja Pharmacy College, Vadakangulam, Tirunelveli, Tamil Nadu, India.

3Accent Pharma, Pipdic Industrial Estate, Mettupalayam, Puducherry, India.

4Immunology Laboratory, Department of Pharmacy, Annamalai University, Annamalai Nagar, Tamil Nadu, India. 

Received: 24th March, 2024; Revised: 12th July, 2024; Accepted: 09th August, 2024; Available Online: 25th September, 2024

ABSTRACT

For the formulation of enteric-coated tablets containing irinotecan hydrochloride, this thesis focuses on HPMC and ethylcellulose, both of which are pH- and oxidation-resistant polymers. The integrated polymer-drug tablet mixture was coated with 15% of eudragit S100 and L100, which is a methacrylic acid copolymers, that’s soluble at pH 7. Both the physical characteristics with the invitro release kinetics pattern of the enteric-coated tablets were characterized. In the invitro release study, different pH environments were used, comparable to the gastrointestinal tract (GIT): 0.1 N HCl solution for two hours, pH 6.8 phosphate buffer for three hours, and pH 7.4 phosphate buffer for six hours. Using this device, you can simulate the pH level of the mouth, the digestive tract, and the urinary tract. As a result of consistent release studies, formulation F7 released 88.2% of the drug after 12 hours. Models such as Higuchi, Korsmeyer-Peppas, and zero-order reactions were used to analyze the GIT. This directed the development of a sustained delivery pattern that may be perfect for colonic IRT administration in the eventual treatment of colon cancer. Among the nine formulations, F7 formulated with EC and HPMC extended best sustained release pattern of drug, hence it is suitable for treating colon cancer. Keywords: Irinotecan hydrochloride, colon cancer, hydrophilic polymer, hydrophobic polymer, methacrylic acid copolymer. International Journal of Drug Delivery Technology (2024); DOI: 10.25258/ijddt.14.3.17 How to cite this article: Author Name. Title. International Journal of Drug Delivery Technology. 2024;14(3):1370-1376.

REFERENCES

  1. Elkhodairy KA, Elsaghir HA, Al-Subayiel Formulation of indomethacin colon targeted delivery systems using polysaccharides as carriers by applying liquisolid technique. BioMed Research Inter national. 2014 (1):704362 . doi: 10.1155/2014/704362.
  2. Chourasia MK, Jain SK. Pharmaceutical approaches to colon targeted drug delivery systems. Journal of Pharmacy and Pharmaceutical Sciences. 2003;6(1):33-66.
  3. Hua Physiological and pharmaceutical considerations for rectal drug formulations. Frontiers in pharmacology. 2019;10:1196. doi: 10.3389/fphar.2019.01196.
  4. Arévalo-Pérez R, Maderuelo C, Lanao Recent advances in colon drug delivery systems. Journal of Controlled Release. 2020;327:703-724.doi: 10.1016/j.jconrel.2020.09.026.
  5. Amidon S, Brown JE, Dave Colon-targeted oral drug delivery systems: design trends and approaches. Aaps Pharmscitech. 2015;16:731-741. doi: 10.1208/s12249-015-0350-9.
  6. Banerjee A, Pathak S, Subramanium VD, Dharanivasan G, Murugesan R, Verma Strategies for targeted drug delivery in treatment of colon cancer: current trends and future perspectives. Drug discovery today. 2017;22(8):1224-1232.doi: 10.1016/j.drudis.2017.05.006.
  7. Debotton N, Dahan Applications of polymers as pharmaceutical excipients in solid oral dosage forms. Medicinal research reviews. 2017;37(1):52-97. doi: 10.1002/med.21403.
  8. Cui N, Friend DR, Fedorak RN. A budesonide prodrug accelerates treatment of colitis in rats. Gut. 1994;35(10):1439- 1446. doi: 10.1136/gut.35.10.1439.
  9. Davis SS, Hardy JG, Fara Transit of pharmaceutical dosage forms through the small intestine. Gut. 1986;27(8):886-892.doi: 10.1136/gut.27.8.886.
  10. Lachman L, Herbert A and Liberman J In: The Theory and Practice of Industrial Pharmacy, Varghese publishing House, Hind Rajasthan Building Dadar Mumbai-400001, 1990; 3rd Edn., p.318.
  11. Acharya DR, Patel DB, Patel VV. Development and validation of first order derivative spectrophotometric method for simultaneous estimation dicloxacillin and cefdoxime proxetil in tablet dosage form. Journal of Drug delivery and Therapeutics. 2012;2(1).10.25258/ijpqa.11.1.9.
  12. Vemula SK. Colon specific drug delivery: Effect of eudragit enteric coating on hydroxypropyl methylcellulose matrix tablets of flurbiprofen. Journal of Young pharmacists. 2015;7(4):373- 10.5530/jyp.2015.4.12.
  13. Krishnaiah YS, Karthikeyan RS, Sankar VG, SatyanarayanaThree-layer guar gum matrix tablet formulations for oral controlled delivery of highly soluble trimetazidine dihydrochloride. Journal of controlled release. 2002 May 17;81(1- 2):45-56.doi: 10.1016/s0168-3659(02)00031-7.
  14. Government of India Ministry of Health and Family Welfare In: Indian Pharmacopoeia. Published by Controller of Publication, Delhi. 1996; Vol. II, p.736.
  15. Mundargi RC, Patil SA, Agnihotri SA, Aminabhavi TM. Development of polysaccharide-based colon targeted drug delivery systems for the treatment of amoebiasis. Drug development and industrial 2007;33(3):255-264. doi: 10.1080/03639040600897127.
  16. Hadi MA, Rao NR, Rao AS. Formulation and evaluation of ileo-colonic targeted matrix-mini-tablets of Naproxen for chronotherapeutic treatment of rheumatoid arthritis. Saudi pharmaceutical journal. 2016;24(1):64-73. doi: 10.1016/j. 2015.03.001.
  17. Banjare T, Alexander A, Agrawal P, Bhandarkar A, Bhatt A, Gupta S, Sahu H, Diwedi SD, Sahu P, Sahu SK, Yadav Formulation and evaluation of colon specific matrix tablet of metronidazole. Research Journal of Pharmacy and Technology. 2018;11(5):2040- 2044. https://doi.org/10.5958/0974-360X.2018.00378.5
  18. Maddiboyina B, Hanumanaik M, Nakkala RK, Jhawat V, Rawat P, Alam A, Foudah AI, Alrobaian MM, Shukla R, Singh S, Kesharwani P. Formulation and evaluation of gastro-retentive floating bilayer tablet for the treatment of Heliyon. 2020 13;6(11):e05459. doi: 10.1016/j.heliyon.2020.e05459. PMID:33241144; PMCID: PMC7674293.
  19. Pawar, Pravin & Gautam, Chinanshu. Design, optimization and evaluation of mesalamine matrix tablet for colon drug delivery system. Journal of Pharmaceutical Investigation, 2015; 10.1007/s40005-015-0214-z.
  20. Patra CN, Priya R, Swain S, Jena GK, Panigrahi KC, GhosePharmaceutical significance of Eudragit: A review. Future Journal of Pharmaceutical Sciences. 2017;3(1):33-45.10.1016/j. fjps.2017.02.001
  21. Kumar A, Gulati M, Singh SK, Gowthamarajan K, Prashar R, Mankotia D, Gupta JP, Banerjee M, Sinha S, Awasthi A, CorrieEffect of co-administration of probiotics with guar gum, pectin and eudragit S100 based colon targeted mini tablets containing 5-Fluorouracil for site specific release. Journal of Drug Delivery Science and Technology. 2020;60:102004.
  22. Pasa G, Choudhury PK, Panigrahi G, Maharana Formulation design and optimization of floating matrix tablets of ciprofloxacin HCl by using HPMC and ethyl cellulose with experimental design. International Journal of Pharmaceutical Sciences and Drug Research. 2019:7-15. 10.25004/IJPSDR.2019.110102.
  23. Gunda RK, Suresh Kumar JN, Satyanarayana V, Ameer Pasha SK, Batta S. Formulation design, optimization and evaluation of domperidone maleate gastro retentive floating tablets. Der Pharmaceutical Letters. 2016;8:198-207.
  24. Sharma, Renuka & Walker, Roderick & Pathak, Kamla. Evaluation of the Kinetics and Mechanism of Drug Release from Econazole nitrate Nanosponge Loaded Carbapol Indian journal of pharmaceutical education and research.2011;45:25-31.
  25. Bash, N., & Prakasam, K. Formulation and evaluations of gel containing fluconazole-antifungal agent. International Journal of Drug Development & Research, 2011;3(4):109-128
  26. Wang Z, Zhou X, Mao Z, Ye R, Mo Y, Finlow Synthesis and characterization of biodegradable poly (lactic acid-co-glycine) via direct melt copolymerization. Iranian Polymer Journal. 2008;17:791-798.
  27. Shoaib MH, Tazeen J, Merchant HA, Yousuf RI. Evaluation of drug release kinetics from ibuprofen matrix tablets using Pakistan journal of pharmaceutical sciences. 2006;19(2):119-124.
  28. Gouda R, Baishya H, Qing Z. Application of mathematical models in drug release kinetics of carbidopa and levodopa ER tablets. Journal of developmental drugs.2017;6(02):1-8. 4172/2329-6631.1000171.
  29. Hamzah O, Ali Studying the release characteristics of naproxen sustained release matrix tablet using natural polyelectrolytes. International Journal of Drug Delivery Technology.2019;9:10.25258/ijddt.v9i3.5.