Additive manufacturing of personalized orodispersible warfarin films.

Warfarin is a narrow therapeutic index drug that requires personalized dosing which is currently not achieved by the marketed products. Further, pediatric and geriatric patients may face swallowing problems with solid oral dosage forms. To face these issues, the aim of the present study was to investigate semisolid extrusion 3D printing for production of warfarin containing orodispersible films. Extrusion 3D printing was successfully utilized to produce transparent, smooth and thin, yet flexible and strong orodispersible films containing therapeutic doses of warfarin (3.9-7.4 mg). Excellent linearity (R2 = 0.9996) between the designed sizes of the films and the drug contents was achieved indicating semisolid extrusion 3D printing as a promising way to produce orodispersible warfarin films with personalized doses. This one-step-process utilizes disposable syringes hindering the printing material to be in contact with the printing equipment making it a potential method for on-demand in-hospital compounding.

[1]  Deng-Guang Yu,et al.  A novel fast disintegrating tablet fabricated by three-dimensional printing , 2009, Drug development and industrial pharmacy.

[2]  Stephen E Kimmel,et al.  Warfarin therapy: in need of improvement after all these years , 2008, Expert opinion on pharmacotherapy.

[3]  H. Salem,et al.  In vitro/in vivo evaluation of an optimized fast dissolving oral film containing olanzapine co-amorphous dispersion with selected carboxylic acids , 2016, Drug delivery.

[4]  Jörg Breitkreutz,et al.  Oral drug delivery in personalized medicine: unmet needs and novel approaches. , 2011, International journal of pharmaceutics.

[5]  M. Alexander,et al.  3D printing of five-in-one dose combination polypill with defined immediate and sustained release profiles. , 2015, Journal of controlled release : official journal of the Controlled Release Society.

[6]  Sandeep Arora,et al.  Orally dissolving strips: A new approach to oral drug delivery system , 2013, International journal of pharmaceutical investigation.

[7]  Sitaram Velaga,et al.  Personalisation of warfarin therapy using thermal ink‐jet printing , 2018, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[8]  Determining the Polymer Threshold Amount for Achieving Robust Drug Release from HPMC and HPC Matrix Tablets Containing a High-Dose BCS Class I Model Drug: In Vitro and In Vivo Studies , 2015, AAPS PharmSciTech.

[9]  Maren Preis,et al.  Design and evaluation of bilayered buccal film preparations for local administration of lidocaine hydrochloride. , 2014, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[10]  Catherine Tuleu,et al.  Ink-jet printing versus solvent casting to prepare oral films: Effect on mechanical properties and physical stability. , 2015, International journal of pharmaceutics.

[11]  M. Maurin,et al.  Physical chemical stability of warfarin sodium , 2001, AAPS PharmSci.

[12]  Benard P Dreyer,et al.  Parents' medication administration errors: role of dosing instruments and health literacy. , 2010, Archives of pediatrics & adolescent medicine.

[13]  Jonathan Goole,et al.  3D printing in pharmaceutics: A new tool for designing customized drug delivery systems. , 2016, International journal of pharmaceutics.

[14]  M. Attimarad,et al.  In vitro techniques to evaluate buccal films. , 2013, Journal of controlled release : official journal of the Controlled Release Society.

[15]  O. Wallerman,et al.  Warfarin sensitivity related to CYP2C9, CYP3A5, ABCB1 (MDR1) and other factors , 2004, The Pharmacogenomics Journal.

[16]  Si-Yu Huang,et al.  Oral disintegrating patient-tailored tablets of warfarin sodium produced by 3D printing , 2018, Drug development and industrial pharmacy.

[17]  Kristen K. Reynolds,et al.  Individualizing warfarin therapy. , 2007, Personalized medicine.

[18]  Basel Arafat,et al.  Tailored on demand anti‐coagulant dosing: An in vitro and in vivo evaluation of 3D printed purpose‐designed oral dosage forms , 2018, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[19]  T. De Beer,et al.  Inkjet Printing of Drug-Loaded Mesoporous Silica Nanoparticles—A Platform for Drug Development , 2017, Molecules.

[20]  Maren Preis,et al.  Oromucosal film preparations: classification and characterization methods , 2013, Expert opinion on drug delivery.

[21]  R. Zelkó,et al.  The effect of water on the solid state characteristics of pharmaceutical excipients: Molecular mechanisms, measurement techniques, and quality aspects of final dosage form , 2012, International journal of pharmaceutical investigation.

[22]  Julie Mariam Joshua,et al.  Fast dissolving oral thin films: An effective dosage form for quick releases , 2016 .

[23]  M. Khan,et al.  A new chapter in pharmaceutical manufacturing: 3D‐printed drug products☆, ☆☆ , 2017, Advanced drug delivery reviews.

[24]  H. Goto,et al.  Electrochemical Polymerization of 4,4-Dimethyl-2,2’-Bithiophene in Concentrated Polymer Liquid Crystal Solution , 2017 .

[25]  A. Basit,et al.  3D printing of modified-release aminosalicylate (4-ASA and 5-ASA) tablets. , 2015, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[26]  K. Karlage,et al.  Analysis of drug content and weight uniformity for half-tablets of 6 commonly split medications. , 2009, Journal of managed care pharmacy : JMCP.

[27]  Maren Preis,et al.  Printed Drug-Delivery Systems for Improved Patient Treatment. , 2016, Trends in pharmacological sciences.

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

[29]  Abdul W. Basit,et al.  Personalised dosing: Printing a dose of one's own medicine. , 2015, International journal of pharmaceutics.

[30]  J. Muselík,et al.  Development of Orodispersible Films Containing Benzydamine Hydrochloride Using a Modified Solvent Casting Method , 2018, AAPS PharmSciTech.

[31]  E. Parfenyuk,et al.  Development of Novel Warfarin-Silica Composite for Controlled Drug Release , 2017, Pharmaceutical Research.

[32]  Deng-Guang Yu,et al.  Novel drug delivery devices for providing linear release profiles fabricated by 3DP. , 2009, International journal of pharmaceutics.