The present study focused on the more detailed characterization of chitosan-carrageenan-based matrix tablets with respect to their potential utilization for drug targeting in the intestine. The study systematically dealt with the particular stages of the dissolution process, as well as with different views of the physico-chemical processes involved in these stages. The initial swelling of the tablets in the acidic medium based on the combined microscopy-calorimetry point of view, the pH-induced differences in the erosion and swelling of the tested tablets, and the morphological characterization of the tablets are discussed. The dissolution kinetics correlated with the rheological properties and mucoadhesive behavior of the tablets are also reported, and, correspondingly, the formulations with suitable properties were identified. It was confirmed that the formation of the chitosan-carrageenan polyelectrolyte complex may be an elegant and beneficial alternative solution for the drug targeting to the intestine by the matrix tablet.

Department of Analytical Chemistry Faculty of Chemical Technology University of Pardubice Studentská 95 532 10 Pardubice Czech Republic

Department of Pharmaceutical Technology Faculty of Pharmacy in Hradec Králové Charles University Akademika Heyrovského 1203 500 05 Hradec Králové Czech Republic

Department of Physical Chemistry Faculty of Chemical Technology University of Pardubice Studentská 95 532 10 Pardubice Czech Republic

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Rinaudo M. Chitin and chitosan—Properties and applications. Cheminform. 2007;31:603–632. doi: 10.1002/chin.200727270. DOI

Duttagupta D.S., Jadhav V.M., Kadam V.J. Chitosan: A propitious biopolymer for drug delivery. Curr. Drug. Deliv. 2015;12:369–381. doi: 10.2174/1567201812666150310151657. PubMed DOI

Hejazi R., Amiji M. Chitosan-based gastrointestinal delivery systems. J. Control. Release. 2003;89:151–165. doi: 10.1016/S0168-3659(03)00126-3. PubMed DOI

Kumar M.N., Muzzarelli R.A., Muzzarelli C., Sashiwa H., Domb A.J. Chitosan chemistry and pharmaceutical perspectives. Chem. Rev. 2004;104:6017–6084. doi: 10.1021/cr030441b. PubMed DOI

Sun X., Liu C., Omer A.M., Yang L.-Y., Ouyang X. Dual-layered pH-sensitive alginate/chitosan/kappa-carrageenan microbeads for colon-targeted release of 5-fluorouracil. Int. J. Biol. Macromol. 2019;132:487–494. doi: 10.1016/j.ijbiomac.2019.03.225. PubMed DOI

Liu J., Zhan X., Wan J., Wang Y., Wang C. Review for carrageenan-based pharmaceutical biomaterials: Favourable physical features versus adverse biological effects. Carbohydr. Polym. 2015;121:27–36. doi: 10.1016/j.carbpol.2014.11.063. PubMed DOI

Picker-Freyer K.M. Carrageenans in solid dosage form design. In: Augsburger L.L., Hoag S.W., editors. Pharmaceutical Dosage Forms: Tablets. Volume 2. Informa Heallthcare USA, Inc.; New York, NY, USA: 2008. pp. 469–492.

Pavli M., Baumgartner S., Kos P., Kogej K. Doxazosin-carrageenan interactions: A novel approach for studying drug-polymer interactions and relation to controlled drug release. Int. J. Pharm. 2011;421:110–119. doi: 10.1016/j.ijpharm.2011.09.019. PubMed DOI

Bixler H.J. The carrageenan connection IV. Br. Food J. 1994;96:12–17. doi: 10.1108/00070709410060763. DOI

Necas J., Bartosikova L. Carrageenan: A review. Vet. Med. 2013;58:187–205. doi: 10.17221/6758-VETMED. DOI

Li L., Wang L., Li J., Jiang J., Wang Y., Zhang X., Ding J., Yu T., Mao S. Insights into the mechanisms of chitosan–anionic polymers-based matrix tablets for extended drug release. Int. J. Pharm. 2014;476:253–265. doi: 10.1016/j.ijpharm.2014.09.057. PubMed DOI

Martinsa A.F., Vlcek J., Wigmosta T., Hedayatic M., Reynolds M.M., Popat K.C., Kipper M.J. Chitosan/iota-carrageenan and chitosan/pectin polyelectrolyte multilayer scaffolds with antiadhesive and bactericidal properties. Appl. Surf. Sci. 2020;502:144282. doi: 10.1016/j.apsusc.2019.144282. DOI

Shchipunov Y.A. Structure of Polyelectrolyte Complexes by the Example of Chitosan Hydrogels with lambda-carrageenan. Polym. Sci. Ser. A. 2020;62:54–61. doi: 10.1134/S0965545X20010101. DOI

Abdelbary G.A., Tadros M.I. Design and in vitro/in vivo evaluation of novel nicorandil extended release matrix tablets based on hydrophilic interpolymer complexes and a hydrophobic waxy polymer. Eur. J. Pharm. Biopharm. 2008;69:1019–1028. doi: 10.1016/j.ejpb.2008.01.011. PubMed DOI

Tapia C., Corbalán V., Costa E., Gai M.N., Yazdani-Pedram M. Study of the Release Mechanism of Diltiazem Hydrochloride from Matrices Based on Chitosan-Alginate and Chitosan-Carrageenan Mixtures. Biomacromolecules. 2005;6:2389–2395. doi: 10.1021/bm050227s. PubMed DOI

Tapia C., Escobar Z., Costa E., Sapag-Hagar J., Valenzuela F., Basualto C., Gai M.N., Yazdani-Pedram M. Comparative studies on polyelectrolyte complexes and mixtures of chitosan–alginate and chitosan–carrageenan as prolonged diltiazem chlorhydrate release systems. Eur. J. Pharm. Biopharm. 2004;57:65–75. doi: 10.1016/S0939-6411(03)00153-X. PubMed DOI

Shao Y., Li L., Gu X., Wang L., Mao S. Evaluation of chitosaneanionic polymers based tablets for extended-release of highly watersoluble drugs. Asian J. Pharm. Sci. 2015;10:24–30. doi: 10.1016/j.ajps.2014.08.002. DOI

Kos P., Pavli M., Baumgartner S., Kogej K. Release mechanism of doxazosin from carrageenan matrix tablets: Effect of ionic strength and addition of sodium dodecyl sulphate. Int. J. Pharm. 2017;529:557–567. doi: 10.1016/j.ijpharm.2017.06.067. PubMed DOI

Kelemen A., Buchholcz G., Sovány T., Pintye-Hód K. Evaluation of the swelling behaviour of iota-carrageenan in monolithic matrix tablets. J. Pharm. Biomed. Anal. 2015;112:85–88. doi: 10.1016/j.jpba.2015.04.025. PubMed DOI

Yin X., Li L., Gu X., Wang H., Wu L., Qin W., Xiao T., York P., Zhang J., Mao S. Dynamic structure model of polyelectrolyte complex based controlled release matrix tablets visualized by synchrotron radiation micro-computed tomography. Mater. Sci. Eng. C. 2020;116:111137. doi: 10.1016/j.msec.2020.111137. PubMed DOI

Abd-El-Gawad A., Ramadan E., Soliman O., Yusif R. Formulation and in-vivo study of ketoprofen tablets prepared using chitosan interpolymer complexes. Bull. Pharm. Sci. 2012;35:1–16. doi: 10.21608/bfsa.2012.64124. DOI

Meng F., Zhou Y., Liu J.Y., Wu J., Wang G., Li R., Zhang Y. Thermal decomposition behaviors and kinetics of carrageenan-poly vinyl alcohol bio-composite film. Carbohydr. Polym. 2018;201:96–104. doi: 10.1016/j.carbpol.2018.07.095. PubMed DOI

Al-Nahdi M., Al-Alawi A., Al-Marhobi I. The Effect of Extraction Conditions on Chemical and Thermal Characteristics of Kappa-Carrageenan Extracted from Hypnea bryoides. J. Mar. Sci. 2019;2019:5183261. doi: 10.1155/2019/5183261. DOI

Ma S., Chen L., Liu X., Li D., Ye N., Wang L. Thermal Behavior of Carrageenan: Kinetic and Characteristic Studies. Int. J. Green Energy. 2012;9:13–21. doi: 10.1080/15435075.2011.617018. DOI

Mishra D.K., Tripathy J., Behari K. Synthesis of graft copolymer (κ-carrageenan-g-N,N-dimethylacrylamide) and studies of metal ion uptake, swelling capacity and flocculation properties. Carbohydr. Polym. 2008;71:524–534. doi: 10.1016/j.carbpol.2007.06.021. DOI

Freile-Pelegrin Y., Azamar J.A., Robledo D. Preliminary characterization of carrageenan from the red seaweed Halymenia floresii. J. Aquat. Food Prod. Technol. 2011;20:73–83. doi: 10.1080/10498850.2010.541590. DOI

Kaminska-Dworznicka A., Antczak A., Samborska K., Lenart A. Acid hydrolysis of kappa-carrageenan as a way of gaining new substances for freezing process modification and protection from excessive recrystallisation of ice. Int. J. Food Sci. Technol. 2015;50:1799–1806. doi: 10.1111/ijfs.12820. DOI

Meinita M.D.N., Marhaeni B., Jeong G.-T., Hong Y.-K. Sequential acid and enzymatic hydrolysis of carrageenan solid waste for bioethanol production: A biorefinery approach. J. Appl. Phycol. 2019;31:2507–2515. doi: 10.1007/s10811-019-1755-8. DOI

Singh S.K., Jacobsson S.P. Kinetics of acid hydrolysis of κ-carageenan as determined by molecular weight (SEC-MALLS-RI), gel breaking strength, and viscosity measurements. Carbohydr. Polym. 1994;23:89–103. doi: 10.1016/0144-8617(94)90032-9. DOI

Nasonova A., Cohen Y., Poverenov E., Borisover M. Binding interactions of salicylic acid with chitosan and its N-alkylated derivative in solutions: An equilibrium dialysis study. Colloids Surf. A. 2020;603:125202. doi: 10.1016/j.colsurfa.2020.125202. DOI

Langer R. New methods of drug delivery. Science. 1990;249:1527–1533. doi: 10.1126/science.2218494. PubMed DOI

Siepmann J., Siepmann F. Modeling of diffusion controlled drug delivery. J. Control. Release. 2012;161:351–362. doi: 10.1016/j.jconrel.2011.10.006. PubMed DOI

Maderuelo C., Zarzuelo A., Lanao J.M. Critical factors in the release of drugs from sustained release hydrophilic matrices. J. Control. Release. 2011;154:2–19. doi: 10.1016/j.jconrel.2011.04.002. PubMed DOI

Ghafourian T., Safari A., Adibkia K., Parviz F., Nokhodchi A. A drug release study from hydroxypropylmethylcellulose (HPMC) matrices using QSPR modeling. J. Pharm. Sci. 2007;96:3334–3351. doi: 10.1002/jps.20990. PubMed DOI

Li L., Wang L., Shao Y., Ni R., Zhang T., Mao S. Drug release characteristics from chitosan-alginate matrix tablets based on the theory of self-assembled film. Int. J. Pharm. 2013;450:197–207. doi: 10.1016/j.ijpharm.2013.04.052. PubMed DOI

Aguzzi C., Bonferoni M.C., Fortich M.R.O., Rossi S., Ferrari F., Caramella C. Influence of complex solubility on formulations based on lambda carageenan and basic drugs. AAPS PhramSciTech. 2002;3:83–89. doi: 10.1208/pt030327. PubMed DOI PMC

Da Silva J.B., de Souza Ferreira S.B., Reis A.V., Cook M.T., Bruschi M.L. Assessing Mucoadhesion in Polymer Gels: The Effect of Method Type and Instrument Variables. Polymers. 2018;10:254. doi: 10.3390/polym10030254. PubMed DOI PMC

Baus R.A., Haug M.F., Leichner C., Jelkmann M., Bernkop-Schnürch A. In Vitro–In Vivo Correlation of Mucoadhesion Studies on Buccal Mucosa. Mol. Pharm. 2019;16:2719–2727. doi: 10.1021/acs.molpharmaceut.9b00254. PubMed DOI

Guerini M., Condrò G., Perugini P. Evaluation of the Mucoadhesive Properties of Chitosan-Based Microstructured Lipid Carrier (CH-MLC) Pharmaceutics. 2022;14:170. doi: 10.3390/pharmaceutics14010170. PubMed DOI PMC

Taniguchi K., Kakuta H. Bixalomer, a novel phosphate binder with a small swelling index, improves hyperphosphatemia in chronic kidney disease rat. Eur. J. Pharmacol. 2015;766:129–134. doi: 10.1016/j.ejphar.2015.10.001. PubMed DOI

Carbinatto F.M., De Castro A.D., Evangelista R.C., Cury B.S.F. Insights into the swelling process and drug release mechanisms from cross-linked pectin/high amylose starch matrices. Asian J. Pharm. Sci. 2014;9:27–34. doi: 10.1016/j.ajps.2013.12.002. DOI

Simancas-Herbada R., Fernández-Carballido A., Aparicio-Blanco J., Slowing K., Rubio-Retama J., Lopez-Cabarcos E., Torres-Suarez A.-I. Controlled Release of Highly Hydrophilic Drugs from Novel Poly (MagnesiumAcrylate) Matrix Tablets. Pharmaceutics. 2020;12:174. doi: 10.3390/pharmaceutics12020174. PubMed DOI PMC

Sokar M.S., Hanafy A.S., El-Kamel A.H., El-Gamal S.S. Pulsatile core-in-cup valsartan tablet formulations: In vitro evaluation. Asian J. Pharm. Sci. 2013;8:234–243. doi: 10.1016/j.ajps.2013.09.006. DOI

Skalická B., Matzick K., Komersová A., Svoboda R., Bartoš M., Hromádko L. 3D-Printed Coating of Extended-Release Matrix Tablets: Effective Tool for Prevention of Alcohol-Induced Dose Dumping Effect. Pharmaceutics. 2021;13:2123. doi: 10.3390/pharmaceutics13122123. PubMed DOI PMC

Lochař V., Komersová A., Matzick K., Skalická B., Bartoš M., Mužíková J., Haddouchi S. The effect of alcohol on ionizing and non-ionizing drug release from hydrophilic, lipophilic and dual matrix tablets. Saudi Pharm. J. 2020;28:187–195. doi: 10.1016/j.jsps.2019.11.020. PubMed DOI PMC

Wang Y., Xu P.P., Li X.X., Nie K., Tuo M.F., Kong B., Chen J. Monitoring the hydrolyzation of aspirin during the dissolution testing for aspirin delayed-release tablets with a fiber-optic dissolution system. J. Pharm. Anal. 2012;2:386–389. doi: 10.1016/j.jpha.2012.06.002. PubMed DOI PMC

Hosokawa S., Shukuya K., Sogabe K., Ejima Y., Morinishi T., Hirakawa E., Ohsaki H., Shimosawa T., Tokuhara Y. Novel absorbance peak of gentisic acid following the oxidation reaction. PLoS ONE. 2020;15:e0232263. doi: 10.1371/journal.pone.0232263. PubMed DOI PMC