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Abstract

Colon-Targeted Drug Delivery System (CTDDS) is able to improve local therapeutic effects in the treatment of colon-specific diseases, such as Crohn’s disease, Ulcerative Colitis (UC), and Irritable Bowel Syndrome (IBS). A colon can also be a suitable site for systemic delivery of drugs susceptible to extreme gastric pH, such as peptides and protein therapeutics. The physiological conditions of the gastrointestinal tract and the physicochemical properties of drugs are being considered to develop strategies and approaches to overcome emerging challenges. This review will discuss factors, challenges, strategies, and approaches to developing a colon-targeted drug delivery system.

References

Abbasi, M., Sohail, M., Minhas, M. U., Khan, S., Hussain, Z., Mahmood, A., Shah, S. A., & Kousar, M. (2019). Novel biodegradable pH-sensitive hydrogels: An efficient controlled release system to manage ulcerative colitis. International Journal of Biological Macromolecules, 136, 83–96. https://doi.org/10.1016/j.ijbiomac.2019.06.046

Ahmad, M. Z., Akhter, S., Ahmad, I., Singh, A., Anwar, M., Shamim, M., & Ahmad, F. J. (2012). In vitro and in vivo evaluation of Assam Bora rice starch-based bioadhesive microsphere as a drug carrier for colon targeting. Expert Opinion on Drug Delivery, 9(2), 141–149. https://doi.org/10.1517/17425247.2012.633507

Akhgari, A., Afrasiabi Garekani, H., Sadeghi, F., & Azimaie, M. (2005). Statistical optimization of indomethacin pellets coated with pH-dependent methacrylic polymers for possible colonic drug delivery. International Journal of Pharmaceutics, 305(1), 22–30. https://doi.org/https://doi.org/10.1016/j.ijpharm.2005.08.025

Amidon, S., Brown, J. E., & Dave, V. S. (2015). Colon targeted oral drug delivery systems: Design trends and approaches. AAPS PharmSciTech, 16(4), 731–741. https://doi.org/10.1208/s12249-015-0350-9

Anita, Singh, A., & Dabral, A. (2019). A review on colon -targeted drug delivery system. International Journal of Pharmaceutical Sciences and Research, 10(1): 47-56. doi: 10.13040/IJPSR.0975-8232.10(1).47-56.

Asghar, L. F. A., & Chandran, S. (2006). Multiparticulate formulation approach to colon specific drug delivery: Current perspectives. Journal of Pharmacy and Pharmaceutical Sciences, 9 (3), 327–338.

Bakhru, S. H., Furtado, S., Morello, A. P., & Mathiowitz, E. (2013). Oral delivery of proteins by biodegradable nanoparticles. Advanced Drug Delivery Reviews, 65(6), 811–821. https://doi.org/10.1016/j.addr.2013.04.006

Bose, A., Elyagoby, A., & Wong, T. W. (2014). Oral 5-fluorouracil colon-specific delivery through in vivo pellet coating for colon cancer and aberrant crypt foci treatment. International Journal of Pharmaceutics, 468(1),178–186. https://doi.org/https://doi.org/10.1016/j.ijpharm.2014.04.006

Chaudhary, A., Tiwari, N., Jain, V., & Singh, R. (2011). Microporous bilayer osmotic tablet for colon-specific delivery. European Journal of Pharmaceutics and Biopharmaceutics, 78(1), 134–140. https://doi.org/10.1016/j.ejpb.2011.01.004

Chourasia, M. K., & Jain, S. K. (2003). Pharmaceutical approaches to colon targeted drug delivery systems. Journal of Pharmacy and Pharmaceutical Sciences, 6(1), 33–66.

Dar, M. J., Ali, H., Khan, A., & Khan, G. M. (2017). Polymer-based drug delivery : the quest for local targeting of inflamed intestinal mucosa. Journal of Drug Targeting, 25(7), 582-596 . https://doi.org/10.1080/1061186X.2017.1298601

Deshmukh, R., Harwansh, R. K., Paul, S. Das, & Shukla, R. (2020). Controlled release of sulfasalazine loaded amidated pectin microparticles through Eudragit S 100 coated capsule for management of inflammatory bowel disease. Journal of Drug Delivery Science and Technology, 5 (December 2019). https://doi.org/10.1016/j.jddst.2019.101495

Dugad, A., Nalawade, P., Thakhre, R., Kakade, S. (2018). Colon targeted drug delivery system – A Review. Current Pharma Research, 9(1), 2604-2635.

Feng, K., Wei, Y., Hu, T., Linhardt, R. J., Zong, M., Wu, H. (2020). Colon targeted delivery systems for nutraceuticals: A review of current vehicles, evaluation methods and future prospects. Trends in Food Science & Technology, 102, 203-222. https://doi.org/10.1016/j.tifs.2020.05.019.

Gangurde, H. H, Chordiya, M. A, Tamizharasi, S., Sivakumar, T. (2013). Optimization and in vivo evaluation of mesalamine pH dependent coated pellets for promising ileocecal targeting. Indonesian Journal of Pharmacy, (s.l), 277-288.

Gazzaniga, A., Maroni, A., Sangalli, M. E., & Zema, L. (2006). Time-controlled oral delivery systems for colon- targeting. Expert Opinion on Drug Delivery, 3(5), 583–597. https://doi.org/10.1517/17425247.3.5.583

Gupta, V. K., Gnanarajan, G., & Kothiyal, P. (2012). A review article on colonic targeted drug delivery system. The Phama Innovation, 1(7), 14–24.

Handali, S., Moghimipour, E., Rezaei, M., Kouchak, M., Ramezani, Z., & Dorkoosh, F. A. (2018). In vitro and in vivo evaluation of coated capsules for colonic delivery. Journal of Drug Delivery Science and Technology, 47(May), 492–498. https://doi.org/10.1016/j.jddst.2018.07.027

Hmar, E. B. L., Paul, S., Zothantluanga, J. H., & Sharma, H. K. (2020). Ulcerative colitis : A review on drug delivery strategies. Science Vision, 20(1), 1-15. https://doi.org/10.33493/scivis.20.01.01

Hua, S. (2020). Advances in oral drug delivery for regional targeting in the gastrointestinal tract - influence of physiological, pathophysiological and pharmaceutical factors. Frontiers in Pharmacology, 11:524. https://doi.org/10.3389/fphar.2020.00524

Irianti, M. I., Rahmasari, R., Arifianti, A. E., Iswandana, R. (2020). Non-invasive strategies for protein drug delivery: oral, transdermal, and pulmonary. Journal of Applied Pharmaceutical Science, 10(10):166–179. https://doi.org/ 10.7324/JAPS.2020.1010017

Iswandana, R., Pham, B. T., Suriguga, S., Luangmonkong, T., van Wijk, L. A., Jansen, Y. J. M., Oosterhuis, D., Mutsaers, H. A. M., & Olinga, P. (2020). Murine precision-cut intestinal slices as a potential screening tool for antifibrotic drugs. Inflammatory Bowel Diseases, 26(5), 678–686. https://doi.org/10.1093/ibd/izz329

Iswandana, R., Putri, K. S. S., Dwiputra, R., Yanuari, T., Sari, S. P., & Djajadisastra, J. (2017a). Formulation of chitosan tripolyphosphate-tetrandrine beads using ionic gelation method: In vitro and in vivo evaluation. International Journal of Applied Pharmaceutics, 9(5), 109–115. https://doi.org/10.22159/ijap.2017v9i5.20842

Iswandana, R., Putri, K. S. S., Wulandari, F. R., Najuda, G., Sari, S. P., & Djajadisastra, J. (2018). Preparation of calcium alginate-tetrandrine beads using ionic gelation method as colon targeted dosage form. Journal of Applied Pharmaceutical Science, 8(5), 68–74. https://doi.org/10.7324/JAPS.2018.8509

Iswandana, R., Putri, K. S. S., Sandiata, C. E., Triani, S., Sari, S. P., & Djajadisastra, J. (2017b). Formulation of tetrandrine beads using ionic gelation method ca-pectinate coated pH-sensitive polymers as colon targeted dosage form. Asian Journal of Pharmaceutical and Clinical Research, 10 (10), 90-95. https://doi.org/10.22159/ijap.2017v9i5.20842

Jain, P., Vaidya, A., Jain, R., Shrivastava, S., Khan, T., & Jain, A. (2017). Ethyl cellulose coated chitosan microspheres of metronidazole as potential anti-amoebic agent. Journal of Bionanoscience, 11(6), 599-607. https://doi.org/10.1166/jbns.2017.1483

Jain, V., Shukla, N., & Mahajan, S. C. (2015). Polysaccharides in colon specific drug delivery. Journal of Translational Science, 1(1), 3–11. https://doi.org/10.15761/JTS.1000103

Kang, M. J., Khanal, T., Kim, H. G., Lee, D. H., Yeo, H. K., Lee, Y. S., Ahn, Y. T., Kim, D. H., Jeong, H. G., & Jeong, T. C. (2012). Role of metabolism by human intestinal microflora in geniposide induced toxicity in HepG2 cells. Archives of Pharmacal Research, 35(4), 733–738. https://doi.org/10.1007/s12272-012-0418-y

Kaur, K., & Kim, K. (2009). Studies of chitosan/organic acid/Eudragit® RS/RL-coated system for colonic delivery. International Journal of Pharmaceutics, 366(1–2), 140-148. https://doi.org/10.1016/j.ijpharm.2008.09.006

Kotla, N., Singh, S., Maddiboyina, B., Sunnapu, O., Webster, T. (2016). A novel dissolution media for testing drug release from a nanostructured polysaccharide-based colon specific drug delivery system: an approach to alternative colon media. International Journal of Nanomedicine, 11, 1089-1095. https://doi.org/10.2147/IJN.S97177

Lee, S. H., Bajracharya, R., Min, J. Y., Han, J. W., Park, B. J., & Han, H. K. (2020). Strategic approaches for colon targeted drug delivery: An overview of recent advancements. Pharmaceutics, 12(1), 68. https://doi.org/10.3390/pharmaceutics12010068

Leuva, V. R. (2012). Oral colon specific drug delivery system. Journal of Pharmacy Research, 5(4), 2293–2297. http://jprsolutions.info Li, J., & Mooney, D. J. (2016). Designing hydrogels for controlled drug delivery. Nature Reviews Materials, 1(12), 1–18. https://doi.org/10.1038/natrevmats.2016.71

Liu, L., & Che, B. (2006). Preparation of monolithic osmotic pump system by coating the indented core tablet. European Journal of Pharmaceutics and Biopharmaceutics, 64(2), 180–184. https://doi.org/10.1016/j.ejpb.2006.05.004

Liu, L., & Xu, X. (2008). Preparation of bilayer-core osmotic pump tablet by coating the indented core tablet. International Journal of Pharmaceutics, 352(1–2), 225–230. https://doi.org/10.1016/j.ijpharm.2007.10.047

Macleod, G. S., Fell, J. T., Collett, J. H., Sharma, H. L., & Smith, A. M. (1999). Selective drug delivery to the colon using pectin:chitosan:hydroxypropyl methylcellulose film coated tablets. International Journal of Pharmaceutics, 187(2), 251–257. https://doi.org/10.1016/S0378-5173(99)00196-9

Maroni, A., Zema, L., Curto, M. D. Del, Loreti, G., & Gazzaniga, A. (2010). Oral pulsatile delivery: Rationale and chronopharmaceutical formulations. International Journal of Pharmaceutics, 398(1–2), 1–8. https://doi.org/10.1016/j.ijpharm.2010.07.026

Maroni, A., Zema, L., Loreti, G., Palugan, L., & Gazzaniga, A. (2013). Film coatings for oral pulsatile release. International Journal of Pharmaceutics, 457(2), 362–371. https://doi.org/10.1016/j.ijpharm.2013.03.010

Mura, C., Nácher, A., Merino, V., Merino-Sanjuan, M., Carda, C., Ruiz, A., Manconi, M., Loy, G., Fadda, A. M., & Diez-Sales, O. (2011). N-Succinyl-chitosan systems for 5- aminosalicylic acid colon delivery: In vivo study with TNBS-induced colitis model in rats. International Journal of Pharmaceutics, 416(1), 145–154. https://doi.org/10.1016/j.ijpharm.2011.06.025

Nguyen, M. N. U., Tran, P. H. L., & Tran, T. T. D. (2019). A single-layer film coating for colon targeted oral delivery. International Journal of Pharmaceutics, 559 (June 2018), 402–409. https://doi.org/10.1016/j.ijpharm.2019.01.066

Oshi, M. A., Naeem, M., Bae, J., Kim, J., Lee, J., Hasan, N., Kim, W., Im, E., Jung, Y., & Yoo, J. W. (2018). Colon targeted dexamethasone microcrystals with pH-sensitive chitosan/alginate/Eudragit S multilayers for the treatment of inflammatory bowel disease. Carbohydrate Polymers, 198(June), 434–442. https://doi.org/10.1016/j.carbpol.2018.06.107

Palugan, L., Cerea, M., Zema, L., Gazzaniga, A., & Maroni, A. (2015). Coated pellets for oral colon delivery. Journal of Drug Delivery Science and Technology, 25(February), 1-15. https://doi.org/10.1016/j.jddst.2014.12.003

Patole, V. C., & Pandit, A. P. (2018). Mesalamine-loaded alginate microspheres filled in enteric coated HPMC capsules for local treatment of ulcerative colitis: in vitro and in vivo characterization. Journal of Pharmaceutical Investigation, 48, 257–267. doi: 10.1007/s40005-017-0304-1.

Philip, A. K., & Philip, B. (2010). Colon targeted drug delivery systems: A review on primary and novel approaches. Oman Medical Journal, 25(2), 70–78. https://doi.org/10.5001/omj.2010.24

Politis, S. N., & Rekkas, D. M. (2011). Pelletization processes for pharmaceutical applications: a patent review. Recent Patents on Drug Delivery & Formulation, 5(1), 61–78. https://doi.org/10.2174/187221111794109493

Qiao, M., Zhang, L., Ma, Y., Zhu, J., & Xiao, W. (2013). A novel electrostatic dry coating process for enteric coating of tablets with Eudragit® L100-55. European Journal of Pharmaceutics and Biopharmaceutics, 83(2), 293–300. https://doi.org/10.1016/j.ejpb.2012.10.006

Rana, S. V, Sharma, S., Malik, A., Kaur, J., Prasad, K. K., Sinha, S. K., & Singh, K. (2013). Small intestinal bacterial overgrowth and orocecal transit time in patients of inflammatory bowel disease. Digestive Diseases and Sciences, 58(9), 2594–2598. https://doi.org/10.1007/s10620-013-2694-x

Ray, S. (2019). Advanced colon-specific delivery systems for treating local disorders. Polysaccharide Carriers for Drug Delivery. Elsevier Ltd. https://doi.org/10.1016/B978-0-08-102553-6.00025-8

Sahle, F. F., Gerecke, C., Kleuser, B., & Bodmeier, R. (2017). Formulation and comparative in vitro evaluation of various dexamethasone-loaded pH-sensitive polymeric nanoparticles intended for dermal applications. International Journal of Pharmaceutics, 516(1), 21–31. https://doi.org/https://doi.org/10.1016/j.ijpharm.2016.11.029

Singh, G., Kumar, D., Singh, M., Sharma, D., & Kaur, S. (2012). Emerging techniques and challenges in colon drug delivery systems. Journal of Applied Pharmaceutical Science 2(3), 139-147.

Singh, S., Neelam, Arora, S., & Singla, Y. P. (2015). An overview of multifaceted significance of eudragit polymers in drug delivery systems. Asian Journal of Pharmaceutical and Clinical Research, 8(5), 1–6.

Sanli, O., Ay, N., & Işiklan, N. (2007). Release characteristics of diclofenac sodium from poly (vinyl alcohol)/sodium alginate and poly(vinyl alcohol)-grafted-poly(acrylamide)/sodium alginate blend beads. European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik e.V, 65(2), 204–214. https://doi.org/10.1016/j.ejpb.2006.08.004

Sardo, H. S., Saremnejad, F., Bagheri, S., & Akhgari, A. (2019). A review on 5-aminosalicylic acid colon targeted oral drug delivery systems. International Journal of Pharmaceutics, 558(November 2018), 367–379. https://doi.org/10.1016/j.ijpharm.2019.01.022

Sastry, S. V, & Khan, M. A. (1998). Aqueous based polymeric dispersion: Plackett--Burman design for screening of formulation variables of atenolol gastrointestinal therapeutic system. Pharmaceutica Acta Helvetiae, 73(2), 105–112. https://doi.org/10.1016/s0031-6865(97)00052-6

Shah, H. K., Conkie, J. A., Tait, R. C., Johnson, J. R., & Wilson, C. G. (2011). A novel, biodegradable and reversible polyelectrolyte platform for topical-colonic delivery of pentosan polysulphate. International Journal of Pharmaceutics, 404(1–2), 124–132. https://doi.org/10.1016/j.ijpharm.2010.11.012

Sherwood, L. (2013). Human physiology: from cells to systems. Eighth Edition. Belmont, CA.

Sousa, T., Yadav, V., Zann, V., Borde, A., Abrahamsson, B., & Basit, A. W. (2014). On the colonic bacterial metabolism of Azo-bonded prodrugs of 5-aminosalicylic acid. Journal of Pharmaceutical Sciences, 103(10), 3171–3175. https://doi.org/10.1002/jps.24103

Sinha, V. R., & Kumria, R. (2003). Microbially triggered drug delivery to the colon. European Journal of Pharmaceutical Sciences, 18, 3–18.

Syed, S. M., Farooqui, Z., Mohammed, M., Dureshahwar, K., & Farooqui, M. (2015). Osmotic Drug Delivery System : An Overview. International Journal of Pharmaceutical Research & Allied Sciences, 4(3), 10–20.

Verma, S., Kumar, V., Mishra, D. N., & Singh, S. K. (2012). Colon targeted drug delivery: Current and novel perspectives. International Journal of Pharmaceutical Sciences and Research, 3(05), 1274–1284.

Verma, R. K., Krishna, D. M., & Garg, S. (2002). Formulation aspects in the development of osmotically controlled oral drug delivery systems. Journal of Controlled Release, 79(1– 3), 7–27. https://doi.org/10.1016/S0168-3659(01)00550-8

Wei, H., Qing, D., De-Ying, C., Bai, X., & Li-Fang, F. (2008). In-vitro and in-vivo studies of pectin/ethylcellulosefilm-coated pellets of 5-fluorouracil for colonic targeting. The Journal of Pharmacy and Pharmacology, 60(1), 35–44. https://doi.org/10.1211/jpp.60.1.0005

Wong, T. W., & Nurjaya, S. (2008). Drug release property of chitosan-pectinate beads and its changes under the influence of microwave. European Journal of Pharmaceutics and Biopharmaceutics, 69(1), 176–188. https://doi.org/10.1016/j.ejpb.2007.09.015

Xu, M., Sun, M., Qiao, H., Ping, Q., & Elamin, E. S. (2014). Preparation and evaluation of colon adhesive pellets of 5-aminosalicylic acid. International Journal of Pharmaceutics, 468(1–2), 165–171. https://doi.org/10.1016/j.ijpharm.2014.04.040

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