Author(s): Zainab Fadhel Alsafar, Mohammed Sabar Al-Lami

Email(s): phpg.zainab.fadhil@uobasrah.edu.iq

DOI: 10.52711/0974-360X.2023.00410   

Address: Zainab Fadhel Alsafar1*, Mohammed Sabar Al-Lami1,2
1College of Pharmacy, University of Basrah, Basrah, Iraq.
2College of Pharmacy, National University of Sciences and Technology, Thi Qar, Iraq.
*Corresponding Author

Published In:   Volume - 16,      Issue - 5,     Year - 2023


ABSTRACT:
The field of drug permeation assessment concerning the discovery and development of orally administered medications has generated a lot of attention. Inappropriate properties of some drugs such as poor water solubility, limited stability at various pH, being a substrate to efflux transporter and degradation by intestinal enzyme, resulting in inefficient oral administration. In research on improving oral absorption of drugs, the measurement of drug penetration across the intestinal membrane iscritical because it will determine oral absorption. The main question is: what is the best model for studying medication permeation and absorption? This review article answers this question by explaining many methodologies that used to evaluate oral drug permeability/absorption in drug discovery. We address the most common and unique in-vitro and ex vivo models needed to assess drug permeation, the benefits and drawbacks of each model, and the mechanisms of drug absorption that each model may analyze. Moreover, to clarify the improvement of the non-everted rat gut ex vivo technique that is acting as a promising approach in drug permeation orally.


Cite this article:
Zainab Fadhel Alsafar, Mohammed Sabar Al-Lami. Current and Developing In vitro and Ex vivo models for assessing medication permeability into the gut produce a Systemic effect. Research Journal of Pharmacy and Technology 2023; 16(5):2492-8. doi: 10.52711/0974-360X.2023.00410

Cite(Electronic):
Zainab Fadhel Alsafar, Mohammed Sabar Al-Lami. Current and Developing In vitro and Ex vivo models for assessing medication permeability into the gut produce a Systemic effect. Research Journal of Pharmacy and Technology 2023; 16(5):2492-8. doi: 10.52711/0974-360X.2023.00410   Available on: https://www.rjptonline.org/AbstractView.aspx?PID=2023-16-5-69


REFERENCES:
1.    Homayun B. Lin X. Choi HJ. Challenges and Recent Progress in Oral Drug Delivery Systems for Biopharmaceuticals. Pharmaceutics. 2019; 11(3): 129. doi: 10.3390/pharmaceutics11030129.
2.    Pandey S. Srivastava V. An Overview on Invasomes: Novel Vesicular Carrier for Transdermal Drug Delivery. Res J Topical Cosmetic Sci. 2021; 12(2):107-2. DOI: 10.52711/2321-5844.2021.00015
3.    Viswanathan P. Muralidaran Y. Ragavan G. Challenges in oral drug delivery: a nano-based strategy to overcome, in Nanostructures for oral medicine. Micro and Nano Technol (Elsevier). 2017; 173-201. https://doi.org/10.1016/B978-0-323-47720-8.00008-0
4.    Schoultz I. Keita ÅV. The Intestinal Barrier and Current Techniques for the Assessment of Gut Permeability. Cells. 2020; 9(8): 1909. doi: 10.3390/cells9081909.
5.    Yadav P. Shah S. Tyagi XK. Formulation and Evaluation of Tinidazole Microgel for Skin Delivery. Res J Topical Cosmetic Sci. 2021; 12(1):43-50. DOI: 10.52711/2321-5844.2021.00007
6.    France MM. Turner JR. The mucosal barrier at a glance. J Cell Sci. 2017; 130(2): 307-314.  doi: 10.1242/jcs.193482.
7.    Schoultz I, Keita ÅV. Cellular and Molecular Therapeutic Targets in Inflammatory Bowel Disease-Focusing on Intestinal Barrier Function. Cells. 2019; 8(2): 193. doi: 10.3390/cells8020193.
8.    Antony J. Debroy S. Manisha C. Thomas P. Jeyarani V. Choephel T. In-vitro cell line Models and Assay methods to study the Anti-diabetic Activity. Res J. Pharm. and Technol. 2019; 12(5): 2200-2206. DOI: 10.5958/0974-360X.2019.00367.6
9.    Tsume Y. Mudie DM. Langguth P. Amidon GE. Amidon GL. The Biopharmaceutics Classification System: subclasses for in vivo predictive dissolution (IPD) methodology and IVIVC. Eur J Pharm Sci. 2014; 57: 152-63. doi: 10.1016/j.ejps.2014.01.009.
10.    Mishra VVBK. Bhanja NSB. Panigrahi BB. Development and Evaluation of Nanoemulsion gel for transdermal delivery of Valdecoxib, Res J. Pharm. and Technol 2019; 12(2): 600-610. DOI: 10.5958/0974-360X.2019.00107.0
11.    Charalabidis A. Sfouni M. Bergström C. Macheras P. The Biopharmaceutics Classification System (BCS) and the Biopharmaceutics Drug Disposition Classification System (BDDCS): Beyond guidelines. Int J Pharm. 2019; 566: 264-281. doi: 10.1016/j.ijpharm.2019.05.041.
12.    Jain P. Study of Substitution Vis -A -Vis Molecular Symmetry Effecting Transport Through Cell Membrane of Barbiturate Derivatives; Proposal for Compilation of E-Database as Computational Tool for Drug Activity. Asian J. Res Chem. 2011; 4(11): 1709-1711.
13.    Möller MN. Cuevasanta E. Orrico F. Lopez AC. Thomson L. Denicola A. Diffusion and Transport of Reactive Species Across Cell Membranes. Adv Exp Med Biol. 2019; 1127: 3-19. doi: 10.1007/978-3-030-11488-6_1.
14.    Daga AS. Ingole BD. Kulkarni SS. Biyani KR. Self Emulsifying Drug Delivery System: Hitherto and Novel Approach. Res J. Pharm. Technol. 2012; 5(6): 736-745.
15.    Volpe DA. Advances in cell-based permeability assays to screen drugs for intestinal absorption. Expert Opin Drug Discov. 2020; 15(5): 539-549. doi: 10.1080/17460441.2020.1735347.
16.    di Cagno M. Bibi HA. Bauer-Brandl A. New biomimetic barrier Permeapad™ for efficient investigation of passive permeability of drugs. Eur J Pharm Sci. 2015; 73: 29-34. doi: 10.1016/j.ejps.2015.03.019.
17.    Madgulkar AR. Bhalekar MR. Kapse SB. Paygude BV. Reddi SS. Transdermal Permeation Enhancement of Valsartan Using Solid Lipid Nanoparticles. Res J. Pharm. Technol. 2011; 4(8): 1297-1302.
18.    Berben P. Bauer-Brandl A. Brandl M. Faller B. Flaten GE. et al. Drug permeability profiling using cell-free permeation tools: Overview and applications. Eur J Pharm Sci. 2018; 119: 219-233. doi: 10.1016/j.ejps.2018.04.016.
19.    Ghadge TA. Kulkarni AS. Majumdar SH. Chavare SD. Ethosome: A Promising Approach for Antifungal Drug Delivery. Res J. Topical Cosmetic Sci. 2015; 6(1): 32-37. DOI: 10.5958/2321-5844.2015.00005.9
20.    Babadi D. Dadashzadeh S. Osouli M. Daryabari MS. Haeri A. Nanoformulation strategies for improving intestinal permeability of drugs: A more precise look at permeability assessment methods and pharmacokinetic properties changes. J Control Release. 202; 321: 669-709. doi: 10.1016/j.jconrel.2020.02.041.
21.    Shekhawat P. Pokharkar V. Risk assessment and QbD based optimization of an Eprosartan mesylate nanosuspension: In-vitro characterization, PAMPA and in-vivo assessment. Int J Pharm. 2019; 567: 118415. doi: 10.1016/j.ijpharm.2019.06.006.
22.    Hate SS. Mosquera-Giraldo LI. Taylor LS. A Mechanistic Study of Drug Mass Transport from Supersaturated Solutions Across PAMPA Membranes. J Pharma Sci., 2022; 111(1): 102-115. https://doi.org/10.1016/j.xphs.2021.07.003.
23.    Faller B. Artificial membrane assays to assess permeability. Curr Drug Metab. 2008; 9(9): 886-892. doi: 10.2174/138920008786485227.
24.    Reis JM. Sinkó B. Serra CH. Parallel artificial membrane permeability assay (PAMPA) - Is it better than Caco-2 for human passive permeability prediction? Mini Rev Med Chem. 2010; 10(11): 1071-1076. doi: 10.2174/1389557511009011071.
25.    Sivajothi R. Karthikeyan K. Analysis of Monthly Rainfall Data Prediction for Change of Economic Environment in Pampadumpara Using Gamma distribution. Res J Pharm. Technol. 2016; 9(9): 1477-1482. DOI: 10.5958/0974-360X.2016.00287.0
26.    Falavigna M. Klitgaard M. Berthelsen R. Müllertz A. Flaten GE. Predicting Oral Absorption of fenofibrate in Lipid-Based Drug Delivery Systems by Combining In Vitro Lipolysis with the Mucus-PVPA Permeability Model. J Pharm Sci. 2021; 110(1): 208-216. doi: 10.1016/j.xphs.2020.08.026.
27.    Banu S. Ramakrishnaiah TN. Screening of Garcinia cambogia for in-Vitro Anti-Cancerous Activity against Colon Adenocarcinoma (Caco-2) Cell Line. Res. J. Pharmacognosy and Phytochem. 2018; 10(4): 272-276.
28.    Jacobsen AC. Nielsen S. Brandl M. Bauer-Brandl A. Drug Permeability Profiling Using the Novel Permeapad® 96-Well Plate. Pharm Res. 2020; 37(6): 93. doi: 10.1007/s11095-020-02807-x.
29.    Nguyen TT. Duong VA. Maeng HJ. Pharmaceutical Formulations with P-Glycoprotein Inhibitory Effect as Promising Approaches for Enhancing Oral Drug Absorption and Bioavailability. Pharmaceutics. 2021; 13(7): 1103. doi: 10.3390/pharmaceutics13071103.
30.    Iftikhar M. Iftikhar A. Zhang H. Gong L. Wang J. Transport, metabolism and remedial potential of functional food extracts (FFEs) in Caco-2 cells monolayer: A review. Food Res Int. 2020. 136: 109240. https://doi.org/10.1016/j.foodres.2020.109240.
31.    Keemink J. Hedge OJ. Bianco V. Hubert M. Bergström CAS. Comparison of Cellular Monolayers and an Artificial Membrane as Absorptive Membranes in the in vitro Lipolysis-permeation Assay. J Pharm Sci. 2022; 111(1): 175-184. doi: 10.1016/j.xphs.2021.09.009.
32.    Varma MV. Khandavilli S. Ashokraj Y. Jain A. Dhanikula A. et al. Biopharmaceutic classification system: a scientific framework for pharmacokinetic optimization in drug research. Curr Drug Metab. 2004; 5(5): 375-88. doi: 10.2174/1389200043335423.
33.    Sun H. Chow EC. Liu S. Du Y. Pang KS. The Caco-2 cell monolayer: usefulness and limitations. Expert Opin Drug Metab Toxicol. 2008; 4(4): 395-411. doi: 10.1517/17425255.4.4.395.
34.    Ashammakhi N. Nasiri R. de Barros NR. Tebon P. et al. Gut-on-a-chip: Current progress and future opportunities. Biomaterials, 2020; 255: 120196. https://doi.org/10.1016/j.biomaterials.2020.120196.
35.    Marrero D. Pujol-Vila F. Vera D. Gabriel G. et al. Gut-on-a-chip: Mimicking and monitoring the human intestine. Biosens Bioelectron. 2021; 181: 113156. doi: 10.1016/j.bios.2021.113156.
36.    Wright L. Barnes TJ. Prestidge CA. Oral delivery of protein-based therapeutics: Gastroprotective strategies, physiological barriers and in vitro permeability prediction. Int J Pharm. 2020; 585: 119488. doi: 10.1016/j.ijpharm.2020.119488.
37.    Balimane PV. Chong S. Morrison RA. Current methodologies used for evaluation of intestinal permeability and absorption. J Pharmacol Toxicol Methods. 2000; 44(1): 301-312. doi: 10.1016/s1056-8719(00)00113-1.
38.    Hintzen F. Laffleur F. Sarti F. Müller C. Bernkop-Schnürch A. et al. In vitro and ex vivo evaluation of an intestinal permeation enhancing self- microemulsifying drug delivery system (SMEDDS). J Drug Deliv Sci Technol. 2013: 23(3): 261-267. https://doi.org/10.1016/S1773-2247(13)50039-6
39.    McCartney F. Jannin V. Chevrier S. Boulghobra H. et al. Labrasol® is an efficacious intestinal permeation enhancer across rat intestine: Ex vivo and in vivo rat studies. J Control Release. 2019; 310: 115-126. doi: 10.1016/j.jconrel.2019.08.008.
40.    Xu Y. Shrestha N. Préat V. Beloqui A. An overview of in vitro, ex vivo and in vivo models for studying the transport of drugs across intestinal barriers. Adv Drug Deliv Rev. 2021; 175: 113795. doi: 10.1016/j.addr.2021.05.005.
41.    Liu W. Pan H. Zhang C, Zhao L. Zhao R. Zhu Y. Pan W. Developments in Methods for Measuring the Intestinal Absorption of Nanoparticle-Bound Drugs. Int J Mol Sci. 2016; 17(7): 1171. doi: 10.3390/ijms17071171.
42.    Dahlgren D. Lennernäs H. Intestinal Permeability and Drug Absorption: Predictive Experimental, Computational and In Vivo Approaches. Pharmaceutics. 2019; 11(8): 411. doi: 10.3390/pharmaceutics11080411.
43.    Tang X. Feng H. Gao J. Bi R. et al. Effect of berbamine hydrochloride on the absorption of berberine hydrochloride in an in situ single-pass intestinal perfusion system in rats. Trop J Pharma Res. 2022; 21(4): 787-794. DOI: 10.4314/tjpr.v21i4.15
44.    Alam MA. Al-Jenoobi FI. Al-Mohizea AM. Everted gut sac model as a tool in pharmaceutical research: limitations and applications. J Pharm Pharmacol. 2012; 64(3): 326-336. doi: 10.1111/j.2042-7158.2011.01391.x.
45.    Tambe A. Mokashi P. Pandita N. Ex-vivo intestinal absorption study of boswellic acid, cyclodextrin complexes and poloxamer solid dispersions using everted gut sac technique. J Pharm Biomed Anal. 2019; 167: 66-73. doi: 10.1016/j.jpba.2018.12.018.
46.    Chaturvedi S. Garg A. Verma A. Nano lipid based carriers for lymphatic voyage of anti- cancer drugs: an insight into the in-vitro, ex-vivo, in-situ and in-vivo study models. J Drug Deliv Sci Technol. 2020; 59: 101899. https://doi.org/10.1016/j.jddst.2020.101899
47.    Ruan LP. Chen S. Yu BY. Zhu DN. Cordell GA. Qiu SX. Prediction of human absorption of natural compounds by the non-everted rat intestinal sac model. Eur J Med Chem. 2006; 41(5): 605-610. doi: 10.1016/j.ejmech.2006.01.013.
48.    Utami RA. Hakiki A. Asyarie S. Retnoningrum DS. Gliadin Peptide Facilitates FITC Dextran Transport across the Non Everted Gut Sac of Rat Small Intestine. Sci Pharm. 2018; 86(2): 13. doi: 10.3390/scipharm86020013.
49.    Sánchez AB. Calpena AC. Mallandrich M. Clares B. Validation of an Ex Vivo Permeation Method for the Intestinal Permeability of Different BCS Drugs and Its Correlation with Caco-2 In Vitro Experiments. Pharmaceutics. 2019; 11(12): 638. doi: 10.3390/pharmaceutics11120638.
50.    Di Lorenzo C. Youssef NN. Diagnosis and management of intestinal motility disorders. Semin Pediatr Surg. 2010; 19(1): 50-58. doi: 10.1053/j.sempedsurg.2009.11.006.
51.    Catterall WA. Voltage-gated calcium channels. Cold Spring Harb Perspect Biol. 2011; 3(8): a003947. doi: 10.1101/cshperspect.a003947.
52.    Dolphin AC. A short history of voltage-gated calcium channels. Br J Pharmacol. 2006;147 Suppl 1(Suppl 1): S56-62. doi: 10.1038/sj.bjp.0706442.
53.    Evans ED, Mangel AW. Depolarization-stimulated contractility of gastrointestinal smooth muscle in calcium-free solution: a review. ISRN Gastroenterol. 2011; 2011: 692528. doi: 10.5402/2011/692528.
54.    Butt A. Khan A. Mazhar W. Khan Q. Uz Z. Maqsood I. Comparison of prokinetic activity of ranitide and neostigmine alone and in combination- an in vitro study. PAFMJ. 2021; 71(Suppl-1): S66-70. https://doi.org/10.51253/pafmj.v71iSuppl-1.2677
55.    Duangjai A. Goh B-H. Lee L-H. Saokaew S. Relaxant effects of Azadirachta indica A. Juss var. siamensis Valeton flower extract on isolated rat ileum contractions and the mechanisms of action. J Trad Compl Med. 2018; 8(4): 515-520. https://doi.org/10.1016/j.jtcme.2018.01.003
56.    Duangjai A. Rukachaisirikul V. Sukpondma Y. Srimaroeng C. Muanprasat C. Antispasmodic Effect of Asperidine B, a Pyrrolidine Derivative, through Inhibition of L-Type Ca2+ Channel in Rat Ileal Smooth Muscle. Molecules. 2021; 26(18): 5492. doi: 10.3390/molecules26185492.
57.    Roberts DJ. Hall RI. Drug absorption, distribution, metabolism and excretion considerations in critically ill adults. Expert Opin Drug Metab Toxicol. 2013; 9(9): 1067-1084. doi: 10.1517/17425255.2013.799137.


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