Speed it up, slow it down…An issue of bicalutamide release from 3D printed tablets.

The article describes the preparation and characterization of 3D-printed tablets with bicalutamide obtained using two-material co-extrusion-based fused deposition modeling (FDM). This method is a modification of typical two-material FDM where separate nozzles are used to print from two filaments. In this work we used a ZMorph® 3D printer with DualPro printhead which allows us to co-extrude two filaments through a single nozzle. This approach gives the opportunity to modify tablet properties in a wide range, especially the dissolution rate, by producing dosage forms with a complex design. The great advantage of this method is that switching between immediate dosage form and controlled release does not require any change in the 3D-printer set-up. We checked the accuracy of co-extrusion printing simply by weighing the amounts of soluble and insoluble material in the printed object as well as calculating the volumes of the printed objects from micro computed tomography (µ-CT) images. We printed several of tablets with a different design including simple one-material tablets, two- and three-compartment tablets with various internal structure and composition of the printing path. The dissolution tests were conducted in sink and non-sink conditions. We obtained tablets with desired bicalutamide dissolution profiles, i.e. immediate, controlled, and combined. The formation of spatial matrix slows down the dissolution in controlled and combined release bicalutamide tablets what was confirmed by µ-CT analysis before and after dissolution.

[1]  Tais Gratieri,et al.  The Digital Pharmacies Era: How 3D Printing Technology Using Fused Deposition Modeling Can Become a Reality , 2019, Pharmaceutics.

[2]  J. Breitkreutz,et al.  Dissolution testing of oral film preparations: Experimental comparison of compendial and non‐compendial methods , 2019, International journal of pharmaceutics.

[3]  P. Kulinowski,et al.  Geometry of modified release formulations during dissolution--influence on performance of dosage forms with diclofenac sodium. , 2014, International journal of pharmaceutics.

[4]  A. Gazzaniga,et al.  3D printed multi‐compartment capsular devices for two‐pulse oral drug delivery , 2017, Journal of controlled release : official journal of the Controlled Release Society.

[5]  Basel Arafat,et al.  Fabricating a Shell-Core Delayed Release Tablet Using Dual FDM 3D Printing for Patient-Centred Therapy , 2016, Pharmaceutical Research.

[6]  Dennis Douroumis,et al.  3D printing applications for transdermal drug delivery , 2018, International journal of pharmaceutics.

[7]  Mariam Ibrahim,et al.  3D Printing of Metformin HCl PVA Tablets by Fused Deposition Modeling: Drug Loading, Tablet Design, and Dissolution Studies , 2019, AAPS PharmSciTech.

[8]  Abdul W. Basit,et al.  Stereolithographic (SLA) 3D printing of oral modified-release dosage forms. , 2016, International journal of pharmaceutics.

[9]  Simon Gaisford,et al.  Selective laser sintering (SLS) 3D printing of medicines. , 2017, International journal of pharmaceutics.

[10]  M. Alexander,et al.  3D printing of tablets containing multiple drugs with defined release profiles. , 2015, International journal of pharmaceutics.

[11]  R. Jachowicz,et al.  Molecular Disorder of Bicalutamide—Amorphous Solid Dispersions Obtained by Solvent Methods , 2018, Pharmaceutics.

[12]  R. Jachowicz,et al.  In vitro and in vivo behavior of ground tadalafil hot-melt extrudates: How the carrier material can effectively assure rapid or controlled drug release. , 2017, International journal of pharmaceutics.

[13]  R. Jachowicz,et al.  Enhanced dissolution of solid dispersions containing bicalutamide subjected to mechanical stress , 2018, International journal of pharmaceutics.

[14]  Waqar Ahmed,et al.  Channelled tablets: An innovative approach to accelerating drug release from 3D printed tablets , 2018, Journal of controlled release : official journal of the Controlled Release Society.

[15]  Renata Jachowicz,et al.  3D printing of tablets containing amorphous aripiprazole by filaments co‐extrusion , 2018, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[16]  Renata Jachowicz,et al.  3D Printing in Pharmaceutical and Medical Applications – Recent Achievements and Challenges , 2018, Pharmaceutical Research.

[17]  Cristiano Quintini,et al.  Three‐dimensional print of a liver for preoperative planning in living donor liver transplantation , 2013, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[18]  3D Printing for Fast Prototyping of Pharmaceutical Dissolution Testing Equipment for Nonstandard Applications , 2018 .

[19]  I. Cockshott Bicalutamide: clinical pharmacokinetics and metabolism. , 2004, Clinical pharmacokinetics.

[20]  M. Cima,et al.  Oral dosage forms fabricated by three dimensional printing. , 2000, Journal of controlled release : official journal of the Controlled Release Society.

[21]  Á. Demeter,et al.  Polymorph transitions of bicalutamide: a remarkable example of mechanical activation. , 2008, Journal of pharmaceutical sciences.

[22]  R. Jachowicz,et al.  Planetary ball milling and supercritical fluid technology as a way to enhance dissolution of bicalutamide. , 2017, International journal of pharmaceutics.

[23]  Griselda Polla,et al.  Conformational polymorphism in bicalutamide. , 2007, International journal of pharmaceutics.

[24]  Maren Preis,et al.  3D-Printed Isoniazid Tablets for the Treatment and Prevention of Tuberculosis—Personalized Dosing and Drug Release , 2019, AAPS PharmSciTech.

[25]  David S. Jones,et al.  Physicochemical characterization of hot melt extruded bicalutamide-polyvinylpyrrolidone solid dispersions. , 2010, Journal of pharmaceutical sciences.

[26]  Ricky D. Wildman,et al.  3D printing of tablets using inkjet with UV photoinitiation. , 2017, International journal of pharmaceutics.

[27]  J. Rantanen,et al.  Roadmap to 3D-Printed Oral Pharmaceutical Dosage Forms: Feedstock Filament Properties and Characterization for Fused Deposition Modeling. , 2019, Journal of pharmaceutical sciences.

[28]  A. Basit,et al.  Fused-filament 3D printing (3DP) for fabrication of tablets. , 2014, International journal of pharmaceutics.

[29]  P. Timmins,et al.  On demand manufacturing of patient‐specific liquid capsules via co‐ordinated 3D printing and liquid dispensing , 2018, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[30]  Dennis Douroumis,et al.  3D Printed “Starmix” Drug Loaded Dosage Forms for Paediatric Applications , 2018, Pharmaceutical Research.

[31]  Simon Gaisford,et al.  3D printed medicines: A new branch of digital healthcare , 2018, International journal of pharmaceutics.

[32]  Mehmet Sakin,et al.  3D Printing of Buildings: Construction of the Sustainable Houses of the Future by BIM , 2017 .

[33]  Simon Gaisford,et al.  Development of modified release 3D printed tablets (printlets) with pharmaceutical excipients using additive manufacturing. , 2017, International journal of pharmaceutics.

[34]  Hao Pan,et al.  Preparation and investigation of controlled-release glipizide novel oral device with three-dimensional printing. , 2017, International journal of pharmaceutics.

[35]  T. Dvir,et al.  Tissue Engineering: 3D Printing of Personalized Thick and Perfusable Cardiac Patches and Hearts (Adv. Sci. 11/2019) , 2019, Advanced Science.

[36]  A. Basit,et al.  Effect of geometry on drug release from 3D printed tablets. , 2015, International journal of pharmaceutics.

[37]  Waqar Ahmed,et al.  Tablet fragmentation without a disintegrant: A novel design approach for accelerating disintegration and drug release from 3D printed cellulosic tablets , 2018, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[38]  Ian Ashcroft,et al.  3D inkjet printing of tablets exploiting bespoke complex geometries for controlled and tuneable drug release , 2017, Journal of controlled release : official journal of the Controlled Release Society.

[39]  Renata Jachowicz,et al.  3D printed orodispersible films with Aripiprazole. , 2017, International journal of pharmaceutics.

[40]  P. Rüegsegger,et al.  A new method for the model‐independent assessment of thickness in three‐dimensional images , 1997 .

[41]  Renata Jachowicz,et al.  PRINTING TECHNIQUES: RECENT DEVELOPMENTS IN PHARMACEUTICAL TECHNOLOGY. , 2017, Acta poloniae pharmaceutica.

[42]  Jukka Rantanen,et al.  Anti‐tuberculosis drug combination for controlled oral delivery using 3D printed compartmental dosage forms: From drug product design to in vivo testing , 2017, Journal of controlled release : official journal of the Controlled Release Society.

[43]  Niklas Sandler,et al.  Three-Dimensional Printed PCL-Based Implantable Prototypes of Medical Devices for Controlled Drug Delivery. , 2016, Journal of pharmaceutical sciences.

[44]  Simon Gaisford,et al.  Direct powder extrusion 3D printing: Fabrication of drug products using a novel single-step process. , 2019, International journal of pharmaceutics.

[45]  H. Kizawa,et al.  Scaffold-free 3D bio-printed human liver tissue stably maintains metabolic functions useful for drug discovery , 2017, Biochemistry and biophysics reports.