A Lower Temperature FDM 3D Printing for the Manufacture of Patient-Specific Immediate Release Tablets
- 2.1k Downloads
The fabrication of ready-to-use immediate release tablets via 3D printing provides a powerful tool to on-demand individualization of dosage form. This work aims to adapt a widely used pharmaceutical grade polymer, polyvinylpyrrolidone (PVP), for instant on-demand production of immediate release tablets via FDM 3D printing.
Dipyridamole or theophylline loaded filaments were produced via processing a physical mixture of API (10%) and PVP in the presence of plasticizer through hot-melt extrusion (HME). Computer software was utilized to design a caplet-shaped tablet. The surface morphology of the printed tablet was assessed using scanning electron microscopy (SEM). The physical form of the drugs and its integrity following an FDM 3D printing were assessed using x-ray powder diffractometry (XRPD), thermal analysis and HPLC. In vitro drug release studies for all 3D printed tablets were conducted in a USP II dissolution apparatus.
Bridging 3D printing process with HME in the presence of a thermostable filler, talc, enabled the fabrication of immediate release tablets at temperatures as low as 110°C. The integrity of two model drugs was maintained following HME and FDM 3D printing. XRPD indicated that a portion of the loaded theophylline remained crystalline in the tablet. The fabricated tablets demonstrated excellent mechanical properties, acceptable in-batch variability and an immediate in vitro release pattern.
Combining the advantages of PVP as an impeding polymer with FDM 3D printing at low temperatures, this approach holds a potential in expanding the spectrum of drugs that could be used in FDM 3D printing for on demand manufacturing of individualised dosage forms.
KEY WORDSfused filament fabrication HME immediate release patient-specific
Active pharmaceutical ingredient
Computer aided design
Differential scanning calorimetry
Fused deposition modelling
Hot melt extrusion
High performance liquid chromatography
Scanning electron microscopy
Glass transition temperature
Thermal gravimetric analysis
X-ray powder diffractometry
ACKNOWLEDGMENTS AND DISCLOSURES
The authors would like to thank UCLAN Innovation Team for their support and Mrs Rim Arafat for her help with graphics design.
- 3.Aprecia. Zipdose® technology. 12/3/2015. Available from: https://aprecia.com/zipdose-platform/zipdose-technology.php.
- 4.McLean S, Sheikh A, Cresswell K, Nurmatov U, Mukherjee M, Hemmi A, Pagliari C. The impact of telehealthcare on the quality and safety of care: a systematic overview. Plos One. 2013;8(8).Google Scholar
- 5.Sanderson K. 3D printing: the future of manufacturing medicine? Pharm J. 2015;7865.Google Scholar
- 11.Boetker J, Water JJ, Aho J, Arnfast L, Bohr A, Rantanen J. Modifying release characteristics from 3D printed drug-eluting products. Eur J Pharm Sci. 2016.Google Scholar
- 15.Marketsandmarkets. Drug delivery technology market. 15/10/2015. Available from: http://www.marketsandmarkets.com/Market-Reports/drug-delivery-technologies-market-1085.html?gclid=CIXRuMT5osQCFe6WtAodmiUAZg.
- 16.GBIResearch. Oral drug delivery market report. 16/11/2015. Available from: http://www.contractpharma.com/issues/2012-06/view_features/oral-drug-delivery-market-report/.
- 18.Knopp MM, Olesen NE, Holm P, Langguth P, Holm R, Rades T. Influence of polymer molecular weight on drug–polymer solubility: a comparison between experimentally determined solubility in PVP and prediction derived from solubility in monomer. J Pharm Sci. 2015;104(9):2905–12.CrossRefPubMedGoogle Scholar
- 19.Shah J, Vasanti S, Anroop B, Vyas H. Enhancement of dissolution rate of valdecoxib by solid dispersions technique with PVP K 30 & PEG 4000: preparation and in vitro evaluation. J Incl Phenom Macrocycl Chem. 2008;63(1):69–75.Google Scholar
- 21.SIGMA-ALDRICH. Theophylline melting point standard. 2016 16/06. Available from: http://www.sigmaaldrich.com/catalog/product/sial/phr1151?lang=en®ion=GB.
- 22.SIGMA-ALDRICH. Dipyridamole. 2016 16/06. Available from: http://www.sigmaaldrich.com/catalog/product/sigma/d9766?lang=en®ion=GB.
- 24.Alsulays BB, Park JB, Alshehri SM, Morott JT, Alshahrani SM, Tiwari RV, et al. Influence of molecular weight of carriers and processing parameters on the extrudability, drug release, and stability of fenofibrate formulations processed by hot-melt extrusion. J Drug Delivery Sci Technol. 2015;29:189–98.CrossRefGoogle Scholar
- 28.Alexander V, Gerasimov MAZ, Gorbatchuk VV, Usmanova LS. Increasing the solubility of dipyridamole using polyethylene glycols. Int J Pharm Pharm Sci. 2014;6(9):244–7.Google Scholar
- 30.Enderle JD, Bronzino JD, Blanchard SM. Introduction to biomedical engineering. Elsevier Academic Press; 2005.Google Scholar
- 31.Yang Z, Yu J, Yang T, Xing H, Zhang J, Xian L, Ding P, Wang D. A method for the preparation of sustained release-coated Metoprolol Succinate pellet-containing tablets. Pharm Dev Technol. 2015:1–8.Google Scholar
- 34.American Pharmacists Association, Quinn ME, Rowe RC, Sheskey PJ. Handbook of pharmaceutical excipients. London: Pharmaceutical Press; 2009.Google Scholar
- 39.Vepuri SB. Studies based on supramolecular chemistry in drug design and improvement of pharmaceutical solids. In. Department of Pharmacy: Acharya Nagarjuna University; 2014. p. 212.Google Scholar
- 41.Makerbot. Replicator 2X Experimental 3D Printer User Manual., http://downloads.makerbot.com/replicator2x/MakerBot_Replicator2X_UserManual_Eng.pdf In. 2013.