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Current Drug Delivery

Editor-in-Chief

ISSN (Print): 1567-2018
ISSN (Online): 1875-5704

Research Article

Evaluation of Extended-release of Piroxicam-loaded Pectin-zein Hydrogel Microspheres: In vitro, Ex vivo, and In vivo Studies

Author(s): Jamshed Bobokalonov*, Zayniddin Muhidinov, Abubakr Nasriddinov, Abduvaly Jomnurodov, Farangis Khojaeva, Gulnora Komilova, Salomudin Yusufi and LinShu Liu

Volume 19, Issue 10, 2022

Published on: 12 May, 2022

Page: [1093 - 1101] Pages: 9

DOI: 10.2174/1567201819666220304092012

Price: $65

Abstract

Objective: This study evaluated drug delivery systems based on Pectin (P) and Zein (Z) hydrogel microspheres. Piroxicam (Px) loaded P/Z hydrogel microspheres (P/Z HM) were developed, and their extended-release pharmacokinetic properties were evaluated.

Methods: Experiments were executed under three different conditions: in vitro, ex vivo, and in vivo. Then, the in vitro-in vivo correlations (IVIVC) and ex vivo-in vivo correlations (EVIVC) were examined.

Results: Analysis of drug release mechanisms were evaluated by fitting the in vitro data into the Ritger- Peppas equation, showing the contribution of both polymers’ relaxation and drug diffusion from the hydrogel microspheres. The fraction absorbed in vivo was determined by the deconvolution of plasma concentration data using the Loo-Riegelman method. After oral single-dose administration of the two formulations, their basic independent model parameters were calculated.

Conclusion: P/Z HM had different drug release behaviors in in vitro and in vivo conditions. However, the ex vivo and in vivo characteristics were similar (R² = 0.99). It seemed reasonable to use the ex vivo method to predict the in vivo drug absorption behavior during the polymeric drug delivery system developmental studies. The P/Z HM formulation maintained the drug dose at the colon site for a long duration and could be applied for delivery of active pharmaceutical and food ingredients to the colon site.

Keywords: Pectin, zein, piroxicam, extended-release, IVIVC, ex vivo-in vivo correlation.

Graphical Abstract

[1]
Ding, H. Chapter 19. Modified-release drug products and drug devices. In: Applied Biopharmaceutics & Pharmacokinetics; Shargel, L.; Yu, A., Eds.; McGraw Hill, 2016.
[2]
Xu, H.; Xu, X.; Li, S.; Song, W-L.; Yu, D-G.; Annie Bligh, S.W. The effect of drug heterogeneous distributions within core-sheath nanostructures on its sustained release profiles. Biomolecules, 2021, 11(9), 1330.
[http://dx.doi.org/10.3390/biom11091330] [PMID: 34572545]
[3]
Yu, Y. Preface to special topic on lattice-based cryptography. Natl. Sci. Rev., 2021, 8(9), b154.
[http://dx.doi.org/10.1093/nsr/nwab154] [PMID: 34691746]
[4]
Mahalak, K.K.; Yan, F.; Liu, L. Pectin-derived vehicle for the controlled delivery of bioactives. ACS Symposium Series, 2020, 1347, 129-139.
[http://dx.doi.org/10.1021/bk-2020-1347.ch007]
[5]
Hu, K.; Huang, X.; Gao, Y.; Huang, X.; Xiao, H.; McClements, D.J. Core-shell biopolymer nanoparticle delivery systems: synthesis and characterization of curcumin fortified zein-pectin nanoparticles. Food Chem., 2015, 182, 275-281.
[http://dx.doi.org/10.1016/j.foodchem.2015.03.009] [PMID: 25842338]
[6]
Huang, X.; Liu, Y.; Zou, Y.; Liang, X.; Peng, Y.; McClements, D.J.; Hu, K. Encapsulation of resveratrol in zein/pectin core-shell nanoparticles: stability, bioaccessibility, and antioxidant capacity after simulated gastrointestinal digestion. Food Hydrocoll., 2019, 93(February), 261-269.
[http://dx.doi.org/10.1016/j.foodhyd.2019.02.039]
[7]
Wang, X.; Peng, F.; Liu, F.; Xiao, Y.; Li, F.; Lei, H.; Wang, J.; Li, M.; Xu, H. Zein-pectin composite nanoparticles as an efficient hyperoside delivery system: fabrication, characterization, and in vitro release property. Lebensm. Wiss. Technol., 2020, 133, 109869.
[http://dx.doi.org/10.1016/j.lwt.2020.109869]
[8]
Feng, S.; Wang, D.; Gan, L.; Shao, P.; Jiang, L.; Sun, P. Preparation and characterization of zein/pectin-based phytosterol nanodispersions and kinetic study of phytosterol release during simulated digestion in vitro. Lebensm. Wiss. Technol., 2020, 128, 109446.
[http://dx.doi.org/10.1016/j.lwt.2020.109446]
[9]
Ropartz, D.; Ralet, M-C. Pectin Structure. In: Pectin: Technological and Physiological Properties; Kontogiorgos, V., Ed.; Springer Interna-tional Publishing: Cham, 2020; pp. 17-36.
[http://dx.doi.org/10.1007/978-3-030-53421-9_2]
[10]
Wójcik-Pastuszka, D.; Potempa, A.; Musiał, W. Bipolymeric pectin millibeads doped with functional polymers as matrices for the controlled and targeted release of mesalazine. Molecules, 2020, 25(23), 5711.
[http://dx.doi.org/10.3390/molecules25235711] [PMID: 33287276]
[11]
Muvva, A.; Chacko, I.A.; Ghate, V.; Lewis, S.A. Modified pectins for colon-specific drug delivery. Indian J. Pharm. Edu. Res., 2020, 54(2s), s12-s18.
[http://dx.doi.org/10.5530/ijper.54.2s.57]
[12]
Zaitseva, O.; Khudyakov, A.; Sergushkina, M.; Solomina, O.; Polezhaeva, T. Pectins as a universal medicine. Fitoterapia, 2020, 146, 104676.
[http://dx.doi.org/10.1016/j.fitote.2020.104676] [PMID: 32561422]
[13]
Mukhidinov, Z.K.; Kasimova, G.F.; Bobokalonov, D.T.; Khalikov, D.Kh.; Teshaev, Kh.I.; Khalikova, M.D.; Liu, L-S. Pectin-zein micro-spheres as drug delivery systems. Pharm. Chem. J., 2011, 44(10), 564-567.
[http://dx.doi.org/10.1007/s11094-011-0518-x]
[14]
Mortensen, A.; Aguilar, F.; Crebelli, R.; Di Domenico, A.; Dusemund, B.; Frutos, M.J.; Galtier, P.; Gott, D.; Gundert-Remy, U.; Lambré, C.; Leblanc, J.C.; Lindtner, O.; Moldeus, P.; Mosesso, P.; Oskarsson, A.; Parent-Massin, D.; Stankovic, I.; Waalkens-Berendsen, I.; Wright, M.; Younes, M.; Tobback, P.; Ioannidou, S.; Tasiopoulou, S.; Woutersen, R.A. Re-evaluation of pectin (E 440i) and amidated pectin (E 440ii) as food additives. EFSA J., 2017, 15(7), e04866.
[http://dx.doi.org/10.2903/j.efsa.2017.4866] [PMID: 32625540]
[15]
Pillay, V.; Danckwerts, M.P.; Muhidinov, Z.; Fassihi, R. Novel modulation of drug delivery using binary zinc-alginate-pectinate polyspheres for zero-order kinetics over several days: experimental design strategy to elucidate the crosslinking mechanism. Drug Dev. Ind. Pharm., 2005, 31(2), 191-207.
[http://dx.doi.org/10.1081/DDC-200047806] [PMID: 15773286]
[16]
Liu, L.; Fishman, M.L.; Hicks, K.B.; Kende, M.; Ruthel, G. Pectin/zein beads for potential colon-specific drug delivery: synthesis and in vitro evaluation. Drug Deliv., 2006, 13(6), 417-423.
[http://dx.doi.org/10.1080/10717540500394935] [PMID: 17002969]
[17]
Labib, G. Overview on zein protein: a promising pharmaceutical excipient in drug delivery systems and tissue engineering. Expert Opin. Drug Deliv., 2018, 15(1), 65-75.
[http://dx.doi.org/10.1080/17425247.2017.1349752] [PMID: 28662354]
[18]
Lao, L.L.; Venkatraman, S.S.; Peppas, N.A. Modeling of drug release from biodegradable polymer blends. Eur. J. Pharm. Biopharm., 2008, 70(3), 796-803.
[http://dx.doi.org/10.1016/j.ejpb.2008.05.024] [PMID: 18577449]
[19]
Siepmann, J.; Siepmann, F. Mathematical modeling of drug delivery. Int. J. Pharm., 2008, 364(2), 328-343.
[http://dx.doi.org/10.1016/j.ijpharm.2008.09.004] [PMID: 18822362]
[20]
Higuchi, T. Mechanism of sustained‐action medication. Theoretical analysis of rate of release of solid drugs dispersed in solid matrices. J. Pharm. Sci., 1963, 52(12), 1145-1149.
[http://dx.doi.org/10.1002/jps.2600521210] [PMID: 14088963]
[21]
Klose, D.; Azaroual, N.; Siepmann, F.; Vermeersch, G.; Siepmann, J. Towards more realistic in vitro release measurement techniques for biodegradable microparticles. Pharm. Res., 2009, 26(3), 691-699.
[http://dx.doi.org/10.1007/s11095-008-9747-4] [PMID: 18958404]
[22]
Sriamornsak, P. Application of pectin in oral drug delivery. Expert Opin. Drug Deliv., 2011, 8(8), 1009-1023.
[http://dx.doi.org/10.1517/17425247.2011.584867] [PMID: 21564000]
[23]
Malinowski, H.; Marroum, P.; Uppoor, V.R.; Gillespie, W.; Ahn, HY.; Lockwood, P.; Henderson, J.; Baweja, R.; Hossain, M.; Fleischer, N. Draft guidance for industry extended-release solid oral dosage forms; Washington, DC, 1997, pp. 269-288.
[http://dx.doi.org/10.1007/978-1-4684-6036-0_25]
[24]
USP 35-NF 30. General information / 1088 in vitro and in vivo evaluation 2012.
[25]
Uppoor, V.R.S. Regulatory perspectives on in vitro (dissolution)/in vivo (bioavailability) correlations. J. Control. Release, 2001, 72(1-3), 127-132.
[http://dx.doi.org/10.1016/S0168-3659(01)00268-1] [PMID: 11389991]
[26]
Warnken, Z.; Puppolo, M.; Hughey, J.; Duarte, I.; Jansen-Varnum, S. In vitro-in vivo correlations of carbamazepine nanodispersions for application in formulation development. J. Pharm. Sci., 2018, 107(1), 453-465.
[http://dx.doi.org/10.1016/j.xphs.2017.10.014] [PMID: 29045883]
[27]
Muhidinov, Z.; Teshaev, K.; Jonmurodov, A.; Khalikov, D.; Fishman, M. Physico-chemical characterization of pectic polysaccharides from various sources obtained by steam assisted flash extraction (SAFE). Macromol. Symp., 2012, 317-318(1), 142-148.
[http://dx.doi.org/10.1002/masy.201100108]
[28]
Shamsara, O.; Jafari, S.M.; Muhidinov, Z.K. Development of double layered emulsion droplets with pectin/β-lactoglobulin complex for bioactive delivery purposes. J. Mol. Liq., 2017, 243, 144-150.
[http://dx.doi.org/10.1016/j.molliq.2017.08.036]
[29]
Bobokalonov, D.T.; Mukhidinov, Z.K.; Rakhimov, I.F.; Khodzhaeva, F.M.; Kasymova, G.F.; Liu, L.S. Piroxicam ex vivo release kinetics from zein/pectin delivery systems. Pharm. Chem. J., 2012, 46(6), 378-380.
[http://dx.doi.org/10.1007/s11094-012-0803-3]
[30]
Guide for the Care and Use of Laboratory Animals; National Academies Press: Washington, D.C., 1996.
[http://dx.doi.org/10.17226/5140]
[31]
Klopas, A.; Panderi, I.; Parissi-Poulou, M. Determination of piroxicam and its major metabolite 5-hydroxypiroxicam in human plasma by zero-crossing first-derivative spectrophotometry. J. Pharm. Biomed. Anal., 1998, 17(3), 515-524.
[http://dx.doi.org/10.1016/S0731-7085(97)00230-6] [PMID: 9656164]
[32]
Roskos, L.K.; Boudinot, F.D. Effects of dose and sex on the pharmacokinetics of piroxicam in the rat. Biopharm. Drug Dispos., 1990, 11(3), 215-225.
[http://dx.doi.org/10.1002/bdd.2510110306] [PMID: 2328308]
[33]
Salmela, L.; Washington, C. A continuous flow method for estimation of drug release rates from emulsion formulations. Int. J. Pharm., 2014, 472(1-2), 276-281.
[http://dx.doi.org/10.1016/j.ijpharm.2014.06.024] [PMID: 24945139]
[34]
Malinowski, H.; Marroum, P.; Uppoor, V.R.; Gillespie, W.; Ahn, H.Y.; Lockwood, P.; Henderson, J.; Baweja, R.; Hossain, M.; Fleischer, N. FDA Guidance for industry extended release solid oral dosage forms: development, evaluation, and application of in vitro/in vivo correlations. Dissolut. Technol., 1997, 4(4), 23-32.
[http://dx.doi.org/10.14227/DT040497P23]
[35]
Limberg, J.; Potthast, H. Regulatory status on the role of in vitro dissolution testing in quality control and biopharmaceutics in Europe. Biopharm. Drug Dispos., 2013, 34(5), 247-253.
[http://dx.doi.org/10.1002/bdd.1844] [PMID: 23585295]
[36]
USFDA Center for Drug Evaluation and Research (CDER). Guidance for industry—extended release oral dosage forms: development, evaluation, and application of in vitro/in vivo correlations Available from: https://www.fda.gov/media/70939/download
[37]
Hugouvieux-Cotte-Pattat, N.; Condemine, G.; Shevchik, V.E. Bacterial pectate lyases, structural and functional diversity. Environ. Microbiol. Rep., 2014, 6(5), 427-440.
[http://dx.doi.org/10.1111/1758-2229.12166] [PMID: 25646533]

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