3D Printing of Metformin HCl PVA Tablets by Fused Deposition Modeling: Drug Loading, Tablet Design, and Dissolution Studies

The main aim of this work was to 3D print metformin HCl–loaded PVA (ML-PVA) tablets by fused deposition modeling. A modified solvent diffusion approach was used to improve drug loading. PVA filaments were placed in metformin HCl solution in ethanol containing low water content (10%(v/v)) to enhance the drug’s solubility. The physicochemical properties of ML-PVA filaments were characterized before and after printing. Lastly, ML-PVA filaments were printed into channeled tablet designs to increase their surface area available for dissolution. The loading of metformin HCl onto PVA filament has significantly increased from 0.08 ± 0.02% in metformin HCl solution in absolute ethanol to 1.40 ± 0.02% in ethanol-water (9:1). The IR spectra of PVA filament soaked in ethanol-water depicted higher peak intensity at 1138 cm−1, indicating higher degree of crystallinity. Thermal analysis of the soaked PVA filaments showed higher melting enthalpies yet lower melting temperature (Tm) compared to unprocessed PVA. ML-PVA filaments were successfully printed into round-channeled tablets (10% infill) with higher surface area and area/volume ratios compared with the solid ones. The inclusion of channels in the tablet design modified their printing pattern causing an unexpected increase in their mass. The dissolution profiles of ML-PVA tablets were mainly dependent on their area/mass ratios. Our results show a simple approach to increase metformin HCl loading onto PVA and reveal the significance of tablet design, infill percentage, and printing pattern as they dictate the area, volume, and the mass of the tablet which impact its dissolution rate.

[1]  Abu T M Serajuddin,et al.  Formulation of 3D Printed Tablet for Rapid Drug Release by Fused Deposition Modeling: Screening Polymers for Drug Release, Drug-Polymer Miscibility and Printability. , 2018, Journal of pharmaceutical sciences.

[2]  A. Basit,et al.  Fused-filament 3D printing of drug products: Microstructure analysis and drug release characteristics of PVA-based caplets. , 2016, International journal of pharmaceutics.

[3]  W. Groenewoud CHAPTER 1 – DIFFERENTIAL SCANNING CALORIMETRY , 2001 .

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

[5]  O. W. Guirguis,et al.  Thermal and structural studies of poly (vinyl alcohol) and hydroxypropyl cellulose blends , 2012 .

[6]  Dennis Douroumis,et al.  Current Trends on Medical and Pharmaceutical Applications of Inkjet Printing Technology , 2016, Pharmaceutical Research.

[7]  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.

[8]  Alexander P. Haring,et al.  Additive manufacturing of pharmaceuticals for precision medicine applications: A review of the promises and perils in implementation , 2018, Additive Manufacturing.

[9]  A. Mansur,et al.  FTIR spectroscopy characterization of poly (vinyl alcohol) hydrogel with different hydrolysis degree and chemically crosslinked with glutaraldehyde , 2008 .

[10]  Ventola Cl Medical Applications for 3D Printing: Current and Projected Uses. , 2014 .

[11]  Federico Parietti,et al.  Hot-melt extruded filaments based on pharmaceutical grade polymers for 3D printing by fused deposition modeling. , 2016, International journal of pharmaceutics.

[12]  K. Fukushige,et al.  3D Printing Factors Important for the Fabrication of Polyvinylalcohol Filament-Based Tablets. , 2017, Biological & pharmaceutical bulletin.

[13]  M. A. Alhnan,et al.  Fabrication of extended-release patient-tailored prednisolone tablets via fused deposition modelling (FDM) 3D printing. , 2015, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

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

[15]  Ricky D. Wildman,et al.  Extrusion 3D Printing of Paracetamol Tablets from a Single Formulation with Tunable Release Profiles Through Control of Tablet Geometry , 2018, AAPS PharmSciTech.

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

[17]  Charles E. Martin,et al.  Pharmaceutical Applications of Hot-Melt Extrusion: Part I , 2007, Drug development and industrial pharmacy.

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

[19]  S. Veesler,et al.  Solvent screening and crystal habit of metformin hydrochloride , 2016 .

[20]  Simon Gaisford,et al.  3D Printing of Medicines: Engineering Novel Oral Devices with Unique Design and Drug Release Characteristics. , 2015, Molecular pharmaceutics.

[21]  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.

[22]  C. Schick,et al.  Crystallization, recrystallization, and melting of polymer crystals on heating and cooling examined with fast scanning calorimetry , 2018, POLYMER CRYSTALLIZATION.

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

[24]  M. Alexander,et al.  Desktop 3D printing of controlled release pharmaceutical bilayer tablets. , 2014, International journal of pharmaceutics.

[25]  O. Tretinnikov,et al.  Determination of the degree of crystallinity of poly(vinyl alcohol) by FTIR spectroscopy , 2012 .

[26]  Hugh Smyth,et al.  3D Printing technologies for drug delivery: a review , 2016, Drug development and industrial pharmacy.

[27]  Hamideh Gholizadeh,et al.  Application of Fused Deposition Modelling (FDM) Method of 3D Printing in Drug Delivery. , 2016, Current pharmaceutical design.

[28]  Nikolaos A. Peppas,et al.  Structure and Applications of Poly(vinyl alcohol) Hydrogels Produced by Conventional Crosslinking or by Freezing/Thawing Methods , 2000 .

[29]  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.

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

[31]  Norio Iwashita,et al.  X-ray Powder Diffraction , 2016 .

[32]  Pamela Robles Martinez,et al.  Influence of Geometry on the Drug Release Profiles of Stereolithographic (SLA) 3D-Printed Tablets , 2018, AAPS PharmSciTech.