Oral drug delivery: Gastrointestinal tract adaptations, barriers and strategies for delivery enhancement - a review

Main Article Content

Omeh Romanus Chijioke
Ugwueze Mercy Ebere
Offiah Raymond Ogbonna
Mbah Chukwuemeka Christian
Momoh Audu Mumuni
Onyishi Ikechukwu Virgilus
Onunkwo Godswill Chukwuemeka
Onyechi Jacob Okechukwu

Abstract

The mouth is a vital route of drug administration with over 84 % of all medicines reportedly administered through it. The gastrointestinal system is equally imbued with a lot of adaptive features that make the oral route even more conducive for systemic drug delivery. The usefulness of the oral route is, however challenged by the existence of numerous absorption barriers which limit the effective absorption and delivery of drugs to their target sites in the body systems. Understanding these adaptive attributes ,systemic barriers, and available strategies for overcoming such barriers will not only be helpful in drug development and design but also useful to the formulation scientists desirous of optimizing drug delivery. The objective of this work was to review the gastrointestinal route of drug administration with respect to some biochemical and physio-anatomic features that impede or enhance drug absorption and to highlight current strategies that have been deployed to achieve optimum per oral drug delivery. The current review reveals the emerging roles of nanocarriers in oral drug delivery. Polymeric nanocarriers enhance the solubility, targeting and safety profiles of many important pharmacological agents. Novel systems that offer protection against gastro enzymes and as such, promote oral ad ministration of biologicals are being widely investigated. Mechanical, magnetic, and acoustic energy – induced membrane perturbation are other delivery options receiving research attentions. It may be concluded that, with the avalanche of research efforts in the area, the oral route will maintain its prominence among other routes of drug administration.

Downloads

Download data is not yet available.

Article Details

How to Cite
Chijioke, O. R., Ebere, U. M., Ogbonna, O. R., Christian, M. C., Mumuni, M. A., Virgilus, O. I., Chukwuemeka, O. G., & Okechukwu, O. J. (2024). Oral drug delivery: Gastrointestinal tract adaptations, barriers and strategies for delivery enhancement - a review . Journal of Biological Research and Biotechnology, 20(3), 1685-1698. https://doi.org/10.4314/br.v20i3.6
Section
Articles
Author Biography

Omeh Romanus Chijioke, Department of Pharmaceutics and Pharmaceutical Technology, Enugu State University of Science and  Technology, Enugu, Enugu State, Nigeria

Department of Pharmaceutical Technology and Industrial Pharmacy, University of Nigeria Nsukka, 
Enugu State, Nigeria

References

Agarwal, V and Khan, M.A. (2001). Current status of the oral delivery of insulin Pharmaceutical Technology. 25 (10). 76-90

Ahmad, N., Alam, M. A., Ahmad, R., Umar, S., and Ahmad, F. (2018). Improvement of oral efficacy of Irinotecan through biodegradable polymeric nanoparticles through in vitro and in vivo investigations. Journal of microencapsulation. 35(4), 327–343.

Albenberg, L. G and Wu, G. D. (2014). Diet and the intestinal microbiome: associations, functions, and implications for health and disease. Gastroenterology 146 (6), 1564–1572.

Alqahtani, M.S., Kazi, M., Alsenaidy, M.A and Ahmad, M.Z. (2021). Advances in oral drug delivery. Frontiers in Pharmacology. https://doi.org/10.3389/fphar.2021.618411

Aulton, M.E. (ed). (2002). Pharmaceutics: The Science of Dosage Form Design. 2nd ed. Churchill. Livingstone. 297 -298.

Bernkop-Schnurch, A. (2005). Thiomers: a new generation of mucoadhesive polymers Advanced Drug Delivery Review., 57(11). 1569-1582

Boegh, M and Nielsen, H.M. (2015). Mucus as a barrier to drug delivery – understanding and mimicking the barrier properties. Basic & Clinical Pharmacology & Toxicology, 116:179–186.

Boyd, B. J., Mark, C. A. S., Vinarov, Z., Kuentz, M., Brouwers, J and Augustijns, P. (2019). Successful oral delivery of poorly watersoluble drugs both depends on the intraluminal behavior of drugs and of appropriate advanced drug delivery systems. European Journal of Pharmaceutical Sciences. 137, 104967. doi:10.1016/j.ejps.2019.104967

Britton, R. A., and Young, V. B. (2014). Role of the intestinal microbiota in resistance to colonization by Clostridium difficile. Gastroenterology 146 (6), 1547–1553.

Brown, D and Tomlin, M. (2010). Competencybased critical care, doi: 10.1007/978-1-84996-146-2-2, Springer-Verlag London Limited 2010

Brunton, L. L., Knollmann, B. C., and Hilal-Dandan, R. (2018). Goodman & Gilman"s: The Pharmacological Basis of Therapeutics. 13th edition (New York: McGraw-Hill Education), 743-756.

Bucovec, P., Benkic P., Smrkoij, M and Vrecer F. (2016). Effects of crystal habit on the dissolution behavior of simvastatin crystals and its relationship to crystallization solvent properties. Pharmacie. 71:263-268.

Chatterjee, B., Almurisi, S.H., Dukhan, A.A.M.,Mandal, U.K and Sengupta, P. (2016). Controversies with self-emulsifying drug delivery system from pharmacokinetic point of view. Journal of Drug Delivery 23(9): 3639-3659.

Dhillon B, Goyal K. N, Malviya R and Sharma K. (2014). Poorly water-soluble drugs: Change in solubility for improved dissolution characteristics a review. Global Journal of Pharmacology 8(1): 26-35.

Dhiman, A.S., (2019). The role of nanotechnology in drug discovery. Drug Discovery World. https://www.ddw-online.com › the-role-of-nanotechnolog. Accessed on July 23rd, 2021.

Effinger, A., O'Driscoll, C.M., McAllister, M. and Fotaki, (2019). Impact of gastrointestinal disease states on oral drug absorption –implications for formulation design – a PEARRL review. Journal of Pharmacy and Pharmacology 17(4)L2714-2726.

Engman, H. (2003) Intestinal barriers to oral drug absorption: Cytochrome P450 3A and ABC-transport proteins (PhD dissertation, Acta Universitatis Upsaliensis). Retrieved from http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-3599

Evans, D. F., Pye, G., Bramley R., Clark, A. G., Dyson T. J and Hardcastel J. D. (1988). Measurement of gastrointestinal pH profiles in normal ambulant human subject. Gut. 29. 1035 – 1041.

Freire, A.C., Basit, A.W., Choudhary, R., Piong, C.W and Merchant, H.A., (2011). Does sex matter? The influence of gender on gastrointestinal physiology and drug delivery. International Journal of pharmacy. 415, 15–28.

Grover, M., Kanazawa, M., Palsson, O. S., Chitkara, D. K., Gangarosa, L. M and Drossman, D. A. (2008). Small intestinal bacterial overgrowth in irritable bowel syndrome: association with colon motility, bowel symptoms, and psychological distress. Neurogastroenterol. Motility. 20 (9),

–1008.

Gurram A.K., Deshpande P. B.,, Kar S. S., Nayak U. Y., Udupa N. and Reddy M. S. (2015). Role of components in the formation of self-microemulsifying drug delivery systems. Indian Journal of Pharmaceutical Sciences. 77(3): 249–257.

Hart M. L., Do DP., Ansari RA and Rizvi S.A.A. (2013) Brief overview of various approaches to enhance drug Solubility. Journal of Developing Drugs 2:115. doi:10.4172/2329-6631.1000115

Hatton, G. B., Madla, C. M., Rabbie, S. C and Basit, A. W. (2018). All disease begins in the gut: Influence of gastrointestinal disorders and surgery on oral drug performance. International Journal of Pharmacy. 548 (1), 408–422. doi: 10.1016/j.ijpharm.2018.06.054

Hatton, G. B., Madla, C. M., Rabbie, S. C and Basit, A. W. (2019). Gut reaction: impact of systemic diseases on gastrointestinal physiology and drug absorption. Drug Discovery Today 24 (2), 417–427. doi: 10.1016/j.drudis.2018.11.009

Homayun, B., Lin, X., and Choi, H. J. (2019). Challenges and Recent Progress in Oral Drug Delivery Systems for Biopharmaceuticals. Pharmaceutics 11 (3), 129. doi: 10.3390/pharmaceutics11030129

Hua, S. (2020). Advances in Oral Drug Delivery for Regional Targeting in the Gastrointestinal tract - Influence of Physiological, Pathophysiological and Pharmaceutical Factors. Frontier in Pharmacology, 28 | https://doi.org/10.3389/fphar.2020.00524

Hua, S., Marks, E., Schneider, J. J and Keely, S. (2015). Advances in oral nano-delivery systems for colon targeted drug delivery in inflammatory bowel disease: selective targeting to diseased versus healthy tissue. Nanomedicine 11 (5), 1117–1132. doi: 10.1016/j.nano.2015.02.018

Jakki, R., Muzammil, A. S., Prabhakar, K and Kishan V. (2013). Development of a selfmicroemulsifying drug delivery system. Acta Pharmaceutical. 63: 241 – 251

Jones, B.L.(2020). Pharmacokinetics in Children. MSD Manual Professional Version Joshi, S. S. Crystal habit modification using habit odifiers. Available at www.Intechopen.com. Accessd 02/ 05/2020 Kalepu, S. and Nekkanti V. (2015). Insoluble drug delivery strategies: review of recent

advances and business prospects. Acta Pharmaceutica Sinica B, 5(5); 441 –453.

Kaur, G., Singh, A., Kaur, A., Kaur, A., Kaur, J and Kaur, H Ggoyal, S. (2015). Efflux transporters: role in drug bioavailability, efflux, and resistance. World Journal of Pharmacy and Pharmaceutical Sciences 4(7): 1780 – 1792.

Khadka, P., Ro, J., Kim, H., Kim, I., Kima J. T., Kim, Hyunil, Cho, J. M., Yun, G., Lee, J. (2014). Pharmaceutical particle technologies: An approach to improve drug solubility, dissolution, and bioavailability. Asian Journal of Pharmaceutical Sciences, 9: 304 - 3 1 6

Khonsary, S. (2017). Guyton and Hall: Textbook of Medical Physiology, https://doi.org/10.4103/sni.sni_327_17.

Kostewicz E.S., Brauns U., Becker R and Dressman JB. (2002). Forecasting the oral absorption behavior of poorly soluble weak bases using solubility and dissolution studies in biorelevant media. Pharmaceutical Research 19:345–9

Kumar, P. and Singh, C. (2013). A study on solubility enhancement methods for poorly water-soluble drugs. American Journal of Pharmacological Sciences, 4:67-73.

Kumar, S. and Singh, P. (2016). Various techniques for solubility enhancement: An overview. The Pharma Innovation Journal. 5(1): 23-28

Kvietys, P. R. (1999). Intestinal physiology relevant to short-bowel syndrome. European Journal of Pediatrics and Surgery. 9 (4), 196–199.

Kyari, M.Z. (2008). extraction and characterization of seed oils. Int. Agrophysics, 22: 139-142.Laffleur F. and Bernkop-Schnürch, A. (2013). Strategies for improving mucosal drug delivery. Nanomedicine. 8 (12):2061-2075.

Lahner, E., Annibale, B and Delle F. G. (2009). Systematic review: impaired drug absorption related to the coadministration of antisecretory therapy. Alimentary Pharmacology and Therapeutics. 29 (12), 1219–1229.

Le Roux, X. Uiroga, N., Walani, M., Arroyo, P and Roca-Cusachs, (2019). The plasma membrane as a mechanochemical transducer, Philosophical Transactions of the Royal Society, 374 (2019) 20180221.

Le J., (n.d). Drug Absorption. MSD Manuals: Available at http;//www.msdmanuals.com/professiona. Accessed on June 5, 2019.

Liu, L., Yao, W., Rao, Y., XiaoY., Lu, X.Y and Gao, J.Q. (2017). pH-Responsive carriers for oral drug delivery: challenges and opportunities of current

platforms. Drug Delivery 1(24); 560 –581.

Loftsson T, Masson M, Brewster ME. (2004). Selfassociation of cyclodextrins. And cyclodextrin complexes. Journal of Pharmaceutical Sciences. 93:1091–9.

Luo, Z, Paunovic, N and Leroux, J. (2021). Physical methods for enhancing drug absorption from the gastrointestinal tract. Advanced Drug Delivery Reviews175: 113814

Magnúsdóttir. A., Másson., M and Loftsson,T.(2002). Journal of Inclusion Phenomena. 44, 213-218.

Managuli, R. S., Raut, S. Y., Reddy, M. S., and Mutalik, S. (2018). Targeting the intestinal lymphatic system: a versatile path for enhanced oral bioavailability of drugs. Expert Opinion. Drug Delivery. 15(8), 787–804.

Marrianne A. (2015). Gastrointestinal tract –physiology and drug absorption. In Aulton M. E. (2015). Aulton’s Pharmaceutics: The design and

manufacture of medicines. (4th ed.) Edinburgh; New York: Churchil Livingstone

Martin D. E. M. (2003). Cyclodextrins and their uses: A review. Process Biochemistry.30(9): 1033-1046.

Mojaverian, P., Vlasses, P.H., Kellner, P.E and Rocci, M.L., (1988). Effects of gender, posture, and age on gastric residence time of an indigestible solid: pharmaceutical considerations. Pharmacy Residence. 5, 639–644.

Momoh, A.M., Kenechukwu C. F., Agbo, C.P., Ugwu, C.E., Adedokun, M.O., Ofomatah, A. C., Omeje E C and Okorie, A.N. (2020). Microemulsionbased approach for oral delivery of insulin: formulation design and characterization. Heliyon. 6(2020): 1 – 8

Moore, J.G., Tweedy, C., Christian, P.E., Datz, F.L. (1983). Effect of age on gastric emptying of liquid–solid meals in man.Digestive Diseases and Sciences. 28, 340–344.

Prajapati, J. B., Verma, S. D., and Patel, A. A. (2018).Oral bioavailability enhancement of agomelatine by loading into nanostructured lipid carriers: Peyer's patch targeting approach. International Journal of Nanomedicine. 13: 35–38. doi: 10.2147/IJN.S124703

Prasad, V., De Jesús, K and Mailankody, S. (2017). The high price of anticancer drugs: origins, implications, barriers, solutions. Nature Reviews Clinical Oncology.14(6):381.

Prego, C., Garcia, M., Torres, D and Alonso, M., J, (2005). Transmucosal Macromolecular Drug Delivery. Journal of. Controlled Release, 101 (1–3): 151-162

Prescott, L.F. (1974). Gastric emptying and drug absorption. British journal of Clinical Pharmacy. 1. 189-190

Rajendrakumar A., Ashok K., Brahmajah B., Nma S and Baburao, C. (2013). The Cyclodextrins: a review. International Journal of Pharmaceutical Research and Bio-Science. 2(2): 291-304.

Rubbens, J., Veiga, R., Brouwers, J and Augustijns, P. (2018). Exploring gastric drug absorption in fasted and fed state rats. International Journal of

Pharmaceutics,548 (1),636–641.

Russell, T.L., Berardi, R.R., Barnett, J.L., Dermentzoglou, L.C., Jarvenpaa, K.M., Schmaltz, S.P and, Dressman, J.B.(1993). Upper gastrointestinal pH in seventy-nine healthy, elderly, North American men and women. Pharmacy Residence 10, 187–196

Russell, T.L., Berardi, R.R., Barnett, J.L.,O’Sullivan, T.L., Wagner, J.G andDressman, J.B., (1994). pH-related changes in the absorption of dipyridamole in the elderly. Pharmacy Residence, 11, 136–143

Savjani K.T., Gajjar H. K and Savjani J.K. Drug (2012). Solubility:Importance and enhancement techniques. International Scholarly Research Network. Doi:10.54`2/2012/195727

Savla R, Browne J, Plassat V, Massan K.M and Wasan E.K. (2017). Review and analysis of FDA approved drugs using lipid-based formulations. Drug

Development and Industrial Pharmacy. 43(11): 1743- 1758.

Sharma, A., Goyal, A. K., and Rath, G. (2018). Development and Characterization of Gastroprotective high-density pellets lodged with zero valent iron nanoparticles. Journal of Pharmaceutical Sciences 107(10), 2663–2673.

Shreya, A. B., Raut, S. Y., Managuli, R. S., Udupa, N., and Mutalik, S. (2018). Active targeting of drugs and bioactive molecules via oral administration by ligand-conjugated lipidic nanocarriers: recent advances. AAPS Pharmaceutical Sciences and Technology. 20 (1):15. doi: 10.1208/s12249-018-1262-2

Shugarts, S., and Benet, L. Z. (2009). The role of transporters in the pharmacokinetics of orally administered drugs. Pharmaceutical Research, 26 (9): 2039– 2054.

Smita, R. and Kamla P. (2014). Recent advances in delivery systems and therapeutics of cinnarizine: a poorly water-soluble drug with absorption window in stomach. Journal of Drug Delivery 2014, Article ID 479246, http://dx.doi.org/10.1155/2014/479246

Srivalli, K.M.R and Lakshmi,P.K.(2012). Overview of P-glycoprotein inhibitors: a rational outlook. Brazilian Journal of Pharmaceutical Sciences, 48 (3), 1123 -1134

Stillhart, C., Vucicevic, K., Augustijns, P., Basit, A.W., Batchelor, H., Flanagan, T.R., Gesquiere, I., Greupink, R., Keszthelyi, D., Koskinen, M., Madla, C.M., Matthys, C., Miljus, G., Mooij, M.G., Parrott, N., Ungell, A.L., de Wildt, S.N., Orlu, M., Klein, S ad Mullertz, A. (2020). Impact of gastrointestinal physiology on drug absorption in special populations–An UNGAP review. European Journal ofPharmaceutical Sciences 147, 105280.

Sunoqrot, S., Hasan, L., Alsadi, A., Hamed, R., and Tarawneh, O. (2017). Interactions of mussel-inspired polymeric nanoparticles with gastric mucin: Implications for gastro-retentive drug delivery. Colloids and Surfaces B: Biointerfaces. 156,1–8.

Szymański P., Markowicz M. And Mikiciuk-Olasik E. (2012). Adaptation of HighThroughput Screening in Drug Discovery—Toxicological Screening

Tests. International Journal of Molecular Science. 13, 427-452.

Thakare P., Mogal V., Borase P., Dusane, J and Kshirsagar S. (2016). A review of selfemulsifying drug delivery system. Pharmaceutical and biological evaluations, 3(2): 140-155.

Thompson, J. S., Quigley, E. M., Adrian, T. E andPath, F. R. (1998). Role of the ileocecal junction in the motor response to intestinal resection. Journal of Gastrointestinal Surgery.2 (2), 174–185. doi: 10.1016/S1091-255X (98)80010-3

Thomson, A. B. R. (1980). Influence of site and unstirred layers on the rate of uptake of cholesterol and fatty acids into rabbit intestine. Journal of. Lipid Research. 21: 1097- 1107.

Thorn, H. A. (2012). First–pass intestinal metabolism of drugs. Experiences from in vitro and simulation studies. Acta Universitatis Upsaliensis. Digital comprehensive summaries of Uppsala dissertations from the faculty of Pharmacy 153. 66. ISBN 978-91-554-8251-0

Titus, R., Kastenmeier, A and Otterson, M. F. (2013). Consequences of gastrointestinal surgery on drug absorption. Nutrition: Clinical Practice

Guidelines, 28(4), 429–436.

Trepat, X., Deng, I., An, S.S., Navajas, D.,Tschumperlin, D. J., Gerthoffer, W. T,. Butler, J.P and Fredberg, J. J. (2007). Universal physical responses to stretch in the living cell. Nature. 447: 592–595,

Tsintavi, P. E., Rekkas, D.Mand Bettini, R (2020). Partial tablet coating by 3D printing. International Journal of Pharmaceutics, 581: 19298

van den Anker J., Reed M.D., Allegaert K andKearns G. L (2018). Developmental changes in pharmacokinetics and pharmacodynamics. Journal of Clinical Pharmacology. 58 (Supplement 10): S10–S25.

Wanigasekara, J and Witharana, C. (2016). Applications of nanotechnology in drug delivery and design - An insight. Current Trends in Biotechnology and Pharmacy,10 (1): 78-91

Williams, H.D., Trevaskis. L. N., Charman, S. A.Shanke, R. M., Charman, W.N. Pouton, C.W. and Porter, C. J. (2013). Strategies to address low drug solubility in discovery and development.Pharmacological Review, 65:315–499.

Wilson F. A. and Kitschy J. M. (1972) Characterization of bile acid absorption across the unstirred water layer and brush border of the rat jejunum. The Journal of Clinical Investigation,51:3015 – 3025.Yang, Q., Ma Y., Zhu J., Chow K and Shi K. (2016).

An update on electrostatic powder

coating for pharmaceuticals.

Particuology,31:1-7.

Yu, X., Wen, T., Cao, P., Shan, L., and Li, L.

(2019). Alginate-chitosan coated

layered double hydroxide

nanocomposites for enhanced oral

vaccine delivery. Journal of Colloid and

Interface Sciences. 556, 258–265.

Zane, P., Guo, Z., Macgerorge, D., Vicat, P and

Olllier, C. (2013). Use of the

pentagastrin dog model to explore food

effects on formulations in early dog

development. European Journal of

Pharmaceutical Sciences. 57, 10.

/j.ejps.2013.09.018

Zhang, G., Wang, C., Wu, L., Xu, J., Hu, X.,

Shailendra Shakya, S., He, Y., Ren, X.,

Chen, W. and Zhang, J. (2018).

Identification of beagle food taking

patterns and protocol for food effects

evaluation on bioavailability. Scientific

Reports 8:12765 | DOI:10.1038/s41598-

-30937-1

Similar Articles

You may also start an advanced similarity search for this article.