Tablets used for extended drug release commonly contain large amounts of drugs. The corresponding drug release mechanism thus has to be well-known and invariable under numerous conditions in order to prevent any uncontrolled drug release. Particularly important is the stability and invariability of the release mechanism in the presence of alcohol due to the possible occurrence of the dose dumping effect. The effect of 3D printing (3DP) coating on the drug release mechanism and the drug release rate was studied as a possible tool for the prevention of the alcohol-induced dose dumping effect. Three types of matrix tablets (hydrophilic, lipophilic, and hydrophilic-lipophilic) were prepared by the direct compression method and coated using 3DP. The commercial filament of polyvinyl alcohol (PVA) and the filament prepared from hypromellose by hot melt extrusion (HME) were used as coating materials. Both coating materials were characterized by SEM, DSC, Raman spectroscopy, and PXRD during particular stages of the processing/coating procedure. The dissolution behavior of the uncoated and coated tablets was studied in the strongly acidic (pH 1.2) and alcoholic (40% of ethanol) dissolution media. The dissolution tests in the alcoholic medium showed that the Affinisol coating was effective in preventing the dose dumping incidence. The dissolution tests in the acidic dissolution media showed that the Affinisol coating can also be useful for the delayed release of active substances.

Center of Materials and Nanotechnologies Faculty of Chemical Technology University of Pardubice Studentská 95 532 10 Pardubice Czech Republic

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

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

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Fuenmayor E., Forde M., Healy A.V., Devine D.M., Lyons J.G., McConville C., Major I. Material Considerations for Fused-Filament Fabrication of Solid Dosage Forms. Pharmaceutics. 2018;10:44. doi: 10.3390/pharmaceutics10020044. PubMed DOI PMC

Solanki N.G., Tahsin M., Shah A.V., Serajuddin A.T. Serajuddin, Formulation of 3D Printed Tablet for Rapid Drug Release by Fused Deposition Modeling: Screening Polymers for Drug Release, Drug-Polymer Miscibility and Printability. J. Pharm. Sci. 2018;107:390–401. doi: 10.1016/j.xphs.2017.10.021. PubMed DOI

Tsintavi E., Rekkas D.M., Bettini R. Partial tablet coating by 3D printing. Int. J. Pharm. 2020;581:119298. doi: 10.1016/j.ijpharm.2020.119298. PubMed DOI

Alruwaili N.K., Rizwanullah M., Bukhari S.N.A., Amir M., Ahmed M.M., Fazil M. 3D Printing Technology in Design of Pharmaceutical Products. Curr. Pharm. Des. 2019;24:5009–5018. doi: 10.2174/1381612825666190116104620. PubMed DOI

Traynor M.J., Brown M., Pannala A., Beck P., Martin G.P. Martin, Influence of alcohol on the release of tramadol from 24-h controlled-release formulations during in vitro dissolution experiments. Drug Dev. Ind. Pharm. 2008;34:885–889. doi: 10.1080/03639040801929240. PubMed DOI

Jedinger N., Schrank S., Mohr S., Feichtinger A., Khinast J., Roblegg E. Alcohol dose dumping: The influence of ethanol on hot-melt extruded pellets comprising solid lipids. Eur. J. Pharm. Biopharm. 2015;92:83–95. doi: 10.1016/j.ejpb.2015.02.022. PubMed DOI

Jedinger N., Khinast J., Roblegg E. The design of controlled-release formulations resistant to alcohol-induced dose dumping—A review. Eur. J. Pharm. Biopharm. 2014;87:217–226. doi: 10.1016/j.ejpb.2014.02.008. PubMed DOI

Lochař V., Komersová A., Matzick K., Slezáková 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

Okwuosa T.C., Pereira B.C., Arafat B., Cieszynska M., Isreb A., Alhnan M.A. Fabricating a shell-core delayed release tablet using dual FDM 3D printing for patient-centred therapy. Pharm. Res. 2017;34:427–437. doi: 10.1007/s11095-016-2073-3. PubMed DOI

AlGahtani M.S., Mohammed A.A., Ahmad J., Saleh E. Development of a 3D printed coating shell to control the drug release of Encapsulated immediate-release tablets. Polymers. 2020;12:1395. doi: 10.3390/polym12061395. PubMed DOI PMC

Raymond C., Rowe P., Sheskey J., Quinn E.M., editors. Handbook of Pharmaceutical Excipients. 6th ed. Pharmaceutical Press; London, UK: 2009.

Xu X., Zhao J., Wang M., Wang L., Yang J. 3D Printed Polyvinyl Alcohol Tablets with Multiple Release Profiles. Sci. Rep. 2019;9:12487. doi: 10.1038/s41598-019-48921-8. PubMed DOI PMC

Salaoru I., Zhou Z., Morris P., Gibbons G. Inkjet-printed Polyvinyl Alcohol Multilayers. J. Vis. Exp. 2017;123:e55093. doi: 10.3791/55093. PubMed DOI PMC

Brochure Pharma Solutions AffinisolTM HPMC HME for Hot Melt Extrusion. [(accessed on 20 October 2021)]. Available online: https://www.pharma.dupont.com/content/dam/dupont/amer/us/en/nutrition-health/general/pharmaceuticals/documents/Download_Affinisol%20HPMC%20HME%20Brochure.pdf.

Tagami T., Fukushige K., Ogawa E., Hayashi N., Ozeki T. 3D Printing Factors Important for the Fabrication of Polyvinylalcohol Filament-Based Tablets. Biol. Pharm. Bull. 2017;40:357–364. doi: 10.1248/bpb.b16-00878. PubMed DOI

Li Z., De Souza L.R., Litina C., Markaki A.E., Al-Tabbaa A. Feasibility of Using 3D Printed Polyvinyl Alcohol (PVA) for Creating Self-Healing Vascular Tunnels in Cement System. Materials. 2019;12:3872. doi: 10.3390/ma12233872. PubMed DOI PMC

Li C.L., Martini L.G., Ford J.L., Roberts M. The use of hypromellose in oral drug delivery. J. Pharm. Pharmacol. 2005;57:533–546. doi: 10.1211/0022357055957. PubMed DOI

Goole J., Amighi K. 3D printing in pharmaceutics: A new tool for designing customized drug delivery systems. Int. J. Pharm. 2016;499:376–394. doi: 10.1016/j.ijpharm.2015.12.071. PubMed DOI

Huang S., O’Donnell K.P., Keen J.M., Rickard M., McGINITY J.W., Williams R.O. A New Extrudable Form of Hypromellose: AFFINISOL™ HPMC HME. AAPS PharmSciTech. 2016;17:106–119. doi: 10.1208/s12249-015-0395-9. PubMed DOI PMC

Gupta S.S., Solanki N., Serajuddin A.T.M. Investigation of thermal and viscoelastic properties of polymers relevant to hot melt extrusion, IV: AffinisolTM HPMC HME polymers. AAPS PharmSciTech. 2016;17:148–157. doi: 10.1208/s12249-015-0426-6. PubMed DOI PMC

FDA (Food and Drug Administration) Guidance for Industry: Bioavailability and Bioequivalence Studies Submitted in NDAs or INDs—General Considerations. [(accessed on 20 October 2021)]. Available online: https://www.gmp-compliance.org/files/guidemgr/UCM389370.pdf.

PrimaselectTM PVA+ Description. [(accessed on 20 October 2021)]. Available online: https://primacreator.com/products/primaselect%E2%84%A2-pva?variant=61779045771.

AFFINISOLTM HPMC HME Brochure. [(accessed on 20 October 2021)]. Available online: https://www.pharma.dupont.com/pharmaceutical-brands/affinisol.html.

Mužíková J., Komersová A., Lochař V., Vildová L., Vošoustová B., Bartoš M. Comparative evaluation of the use of dry binders in a physical mixture or as a coprocessed dry binder in matrix tablets with extended drug release. Acta Pharm. 2018;68:295–311. doi: 10.2478/acph-2018-0030. PubMed DOI

Komersová A., Lochař V., Myslíková K., Mužíková J., Bartoš M. Formulation and dissolution kinetics study of hydrophilic matrix tablets with tramadol hydrochloride and different co-processed dry binders. Eur. J. Pharm. Sci. 2016;95:36–45. doi: 10.1016/j.ejps.2016.08.002. PubMed DOI

Khatri P., Katikaneni P., Desai D., Minko T. Evaluation of Affinisol® HPMC polymers for direct compression proces applications. J. Drug Deliv. Sci. Technol. 2018;47:461–467. doi: 10.1016/j.jddst.2018.08.018. DOI

Rozo J.I.J., Zarow A., Zhou B., Pinal R., Iqbal Z., Romañach R.J. Complementary near-infrared and Raman imaging of pharmaceutical thin films. J. Pharm. Sci. 2011;100:4888–4895. doi: 10.1002/jps.22653. PubMed DOI

Prasad E., Islam M.T., Goodwin D.J., Megarry A.J., Halbert G.W., Florence A.J., Robertson J. Development of a Hot-Melt Extrusion (HME) process to produce drug loaded Affinisol™ 15LV filaments for Fused Filament Fabrication (FFF) 3D printing. Addit. Manuf. 2019;29:100776. doi: 10.1016/j.addma.2019.06.027. DOI

Meena T., Parikh S.S., Gupta A.T.M. Serajuddin, Investigation of thermal and viscoelastic properties of polymers relevant to hot melt extrusion, II: Cellulosic polymers. J. Excip. Food Chem. 2014;5:46–55.

Liu P., Chen W., Liu C., Tian M., Liu P. A novel poly(vinyl alcohol)/poly(ethylene glycol) scaffold for tissue engineering with a unique bimodal open-celled structure fabricated using supercritical fluid foaming. Sci. Rep. 2019;9:9534. doi: 10.1038/s41598-019-46061-7. PubMed DOI PMC

Liao G.-M., Yang C.-C., Hu C.-C., Pai Y.-L., Lue S.J. Novel quaterrnized polyvinyl alcohol/ quaterrnized chitosan nano-composite as an effective hydroxide-conducting electrolyte. J. Membr. Sci. 2015;485:17–29. doi: 10.1016/j.memsci.2015.02.043. DOI

Smyj R., Wang X.-P., Han F. Tramadol Hydrochloride. Profiles Drug Subst. Excip. Relat. Methodol. 2013;38:463–494. doi: 10.1016/B978-0-12-407691-4.00011-3. PubMed DOI

Thermal degradation of Affinisol HPMC: Optimum Processing Temperatures for Hot Melt Extrusion and 3D Printing

Matrix Tablets Based on Chitosan-Carrageenan Polyelectrolyte Complex: Unique Matrices for Drug Targeting in the Intestine