Towards Printed Pediatric Medicines in Hospital Pharmacies: Comparison of 2D and 3D-Printed Orodispersible Warfarin Films with Conventional Oral Powders in Unit Dose Sachets
Tóm tắt
To date, the lack of age-appropriate medicines for many indications results in dose manipulation of commercially available dosage forms, commonly resulting in inaccurate doses. Various printing technologies have recently been explored in the pharmaceutical field due to the flexible and precise nature of the techniques. The aim of this study was, therefore, to compare the currently used method to produce patient-tailored warfarin doses at HUS Pharmacy in Finland with two innovative printing techniques. Dosage forms of various strengths (0.1, 0.5, 1, and 2 mg) were prepared utilizing semisolid extrusion 3D printing, inkjet printing and the established compounding procedure for oral powders in unit dose sachets (OPSs). Orodispersible films (ODFs) drug-loaded with warfarin were prepared by means of printing using hydroxypropylcellulose as a film-forming agent. The OPSs consisted of commercially available warfarin tablets and lactose monohydrate as a filler. The ODFs resulted in thin and flexible films showing acceptable ODF properties. Moreover, the printed ODFs displayed improved drug content compared to the established OPSs. All dosage forms were found to be stable over the one-month stability study and suitable for administration through a naso-gastric tube, thus, enabling administration to all possible patient groups in a hospital ward. This work demonstrates the potential of utilizing printing technologies for the production of on-demand patient-specific doses and further discusses the advantages and limitations of each method.
Từ khóa
Tài liệu tham khảo
Nunn, 2003, Making medicines that children can take, Arch. Dis. Child., 88, 369, 10.1136/adc.88.5.369
Young, 2017, Anticoagulation therapies in children, Pediatr. Clin. N. Am., 64, 1257, 10.1016/j.pcl.2017.08.004
Santos, 2017, Use of warfarin in pediatrics: Clinical and pharmacological characteristics, Rev. Paul. Pediatr., 35, 375, 10.1590/1984-0462/;2017;35;4;00008
Hill, 2016, Analysis of drug content and weight uniformity for half-tablets of 6 commonly split medications, J. Manag. Care Pharm., 15, 253
Helmy, 2016, Tablet splitting: Is it worthwhile? Analysis of drug content and weight uniformity for half tablets of 16 commonly used medications in the outpatient setting, J. Manag. Care Spec. Pharm., 21, 76
Madathilethu, 2018, Content uniformity of quartered hydrocortisone tablets in comparison with mini-tablets for paediatric dosing, BMJ Paediatr. Open, 2, e000198, 10.1136/bmjpo-2017-000198
Watson, 2018, How close is the dose? Manipulation of 10 mg hydrocortisone tablets to provide appropriate doses to children, Int. J. Pharm., 545, 57, 10.1016/j.ijpharm.2018.04.054
Brion, 2010, Extemporaneous (magistral) preparation of oral medicines for children in European hospitals, Acta Paediatr., 92, 486, 10.1111/j.1651-2227.2003.tb00583.x
Visser, 2017, Personalized medicine in pediatrics: The clinical potential of orodispersible films, AAPS PharmSciTech, 18, 267, 10.1208/s12249-016-0515-1
Thabet, 2018, Drug formulations: standards and novel strategies for drug administration in pediatrics, J. Clin. Pharmacol., 58, S26, 10.1002/jcph.1138
Preis, 2015, Orally disintegrating films and mini-tablets—Innovative dosage forms of choice for pediatric use, AAPS PharmSciTech, 16, 234, 10.1208/s12249-015-0313-1
Schobben, 2013, Acceptability of different oral formulations in infants and preschool children, Arch. Dis. Child., 98, 725, 10.1136/archdischild-2012-303303
Klingmann, 2016, Acceptability of mini-tablets in young children: Results from three prospective cross-over studies, AAPS PharmSciTech, 18, 263, 10.1208/s12249-016-0639-3
Orlu, 2017, Acceptability of orodispersible films for delivery of medicines to infants and preschool children, Drug Deliv., 24, 1243, 10.1080/10717544.2017.1370512
Scarpa, 2018, Key acceptability attributes of orodispersible films, Eur. J. Pharm. Biopharm., 125, 131, 10.1016/j.ejpb.2018.01.003
Schliephacke, 2013, Drug-printing by flexographic printing technology—A new manufacturing process for orodispersible films, Int. J. Pharm., 441, 818, 10.1016/j.ijpharm.2012.12.023
Bala, 2013, Orally dissolving strips: A new approach to oral drug delivery system, Int. J. Pharm. Investig., 3, 67, 10.4103/2230-973X.114897
Borges, 2015, Oral films: Current status and future perspectives: I—Galenical development and quality attributes, J. Control. Release, 206, 1, 10.1016/j.jconrel.2015.03.006
Preis, 2015, Perspective: Concepts of printing technologies for oral film formulations, Int. J. Pharm., 494, 578, 10.1016/j.ijpharm.2015.02.032
Scarpa, 2017, Orodispersible films: Towards drug delivery in special populations, Int. J. Pharm., 523, 327, 10.1016/j.ijpharm.2017.03.018
Sandler, 2016, Printed drug-delivery systems for improved patient treatment, Trends Pharmacol. Sci., 37, 1070, 10.1016/j.tips.2016.10.002
Preis, 2017, 3D-printed drugs for children—Are we ready yet?, AAPS PharmSciTech, 18, 303, 10.1208/s12249-016-0704-y
Rahman, 2018, Additive manufacturing with 3D printing: Progress from bench to bedside, AAPS J., 20, 101, 10.1208/s12248-018-0225-6
Trenfield, 2018, 3D printing pharmaceuticals: Drug development to frontline care, Trends Pharmacol. Sci., 39, 440, 10.1016/j.tips.2018.02.006
Awad, 2018, 3D printed medicines: A new branch of digital healthcare, Int. J. Pharm., 548, 586, 10.1016/j.ijpharm.2018.07.024
Zhang, 2019, 3D-printed isoniazid tablets for the treatment and prevention of tuberculosis—Personalized dosing and drug release, AAPS PharmSciTech, 20, 52, 10.1208/s12249-018-1233-7
Goole, 2016, 3D printing in pharmaceutics: A new tool for designing customized drug delivery systems, Int. J. Pharm., 499, 376, 10.1016/j.ijpharm.2015.12.071
Breitkreutz, 2019, On-demand manufacturing of immediate release levetiracetam tablets using pressure-assisted microsyringe printing, Eur. J. Pharm. Biopharm., 134, 29, 10.1016/j.ejpb.2018.11.008
Khaled, 2018, 3D extrusion printing of high drug loading immediate release paracetamol tablets, Int. J. Pharm., 538, 223, 10.1016/j.ijpharm.2018.01.024
Szafraniec, 2018, 3D printing in pharmaceutical and medical—Recent achievements and challenges, Pharm. Res., 35, 176, 10.1007/s11095-018-2454-x
Tian, 2018, Oral disintegrating patient-tailored tablets of warfarin sodium produced by 3D printing, Drug Dev. Ind. Pharm., 44, 1918, 10.1080/03639045.2018.1503291
Vuddanda, 2018, Personalisation of warfarin therapy using thermal ink-jet printing, Eur. J. Pharm. Sci., 117, 80, 10.1016/j.ejps.2018.02.002
Sandler, 2019, Additive manufacturing of personalized orodispersible warfarin films, Int. J. Pharm., 564, 117, 10.1016/j.ijpharm.2019.04.018
Niese, 2019, Formulation development of a continuously manufactured orodispersible film containing warfarin sodium for individualized dosing, Eur. J. Pharm. Biopharm., 136, 93, 10.1016/j.ejpb.2019.01.011
Kovanen, 2017, Challenge of paediatric compounding to solid dosage forms sachets and hard capsules—Finnish perspective, J. Pharm. Pharmacol., 69, 593, 10.1111/jphp.12648
(2017). Pharmacopoeia Europea (Ph. Eur.), edition 9.0, European Directorate for the Quality of Medicines & HealthCare (EDQM).
Garsuch, 2010, Comparative investigations on different polymers for the preparation of fast-dissolving oral films, J. Pharm. Pharmacol., 62, 539, 10.1211/jpp.62.04.0018
Liew, 2012, Characterization of oral disintegrating film containing donepezil for alzheimer disease, AAPS PharmSciTech, 13, 134, 10.1208/s12249-011-9729-4
Gajdziok, 2018, Development of orodispersible films containing benzydamine hydrochloride using a modified solvent casting method, AAPS PharmSciTech, 19, 2509, 10.1208/s12249-018-1088-y
Genina, 2013, Evaluation of different substrates for inkjet printing of rasagiline mesylate, Eur. J. Pharm. Biopharm., 85, 1075, 10.1016/j.ejpb.2013.03.017
Edinger, 2018, QR encoded smart oral dosage forms by inkjet printing, Int. J. Pharm., 536, 138, 10.1016/j.ijpharm.2017.11.052
Visser, 2015, Orodispersible films in individualized pharmacotherapy: The development of a formulation for pharmacy preparations, Int. J. Pharm., 478, 155, 10.1016/j.ijpharm.2014.11.013
Boateng, 2009, Development and mechanical characterization of solvent-cast polymeric films as potential drug delivery systems to mucosal surfaces, Drug Dev. Ind. Pharm., 35, 986, 10.1080/03639040902744704
Szakonyi, 2012, The effect of water on the solid state characteristics of pharmaceutical excipients: Molecular mechanisms, measurement techniques, and quality aspects of final dosage form, Int. J. Pharm. Investig., 2, 18, 10.4103/2230-973X.96922
Hoffmann, 2011, Advances in orodispersible films for drug delivery, Expert Opin. Drug Deliv., 8, 299, 10.1517/17425247.2011.553217
Liew, 2014, Effect of polymer, plasticizer and filler on orally disintegrating film, Drug Dev. Ind. Pharm., 40, 110, 10.3109/03639045.2012.749889
Ashland KlucelTM (2018, August 22). Hydroxypropylcellulose—Physical and Chemical Properties for Pharmaceutical Applications. Available online: https://www.ashland.com/file_source/Ashland/Product/Documents/Pharmaceutical/PC_11229_Klucel_HPC.pdf.
ElMeshad, 2011, Characterization and optimization of orodispersible mosapride film formulations, AAPS PharmSciTech, 12, 1384, 10.1208/s12249-011-9713-z
Nair, 2013, In vitro techniques to evaluate buccal films, J. Control. Release, 166, 10, 10.1016/j.jconrel.2012.11.019
DFE (2019, April 03). Pharma Lactose Some Basic Properties and Characteristics. Available online: https://www.dfepharma.com/-/media/documents/technical-documents/technical-papers/lactose-some-basic-properties.pdf.
Thabet, 2018, Continuous manufacturing and analytical characterization of fixed-dose, multilayer orodispersible films, Eur. J. Pharm. Sci., 117, 236, 10.1016/j.ejps.2018.02.030
Kurek, 2017, 3D printed orodispersible films with Aripiprazole, Int. J. Pharm., 533, 413, 10.1016/j.ijpharm.2017.05.052
Sandler, 2011, Inkjet printing of drug substances and use of porous substrates-towards individualized dosing, J. Pharm. Sci., 100, 3386, 10.1002/jps.22526
Genina, 2012, Tailoring controlled-release oral dosage forms by combining inkjet and flexographic printing techniques, Eur. J. Pharm. Sci., 47, 615, 10.1016/j.ejps.2012.07.020
Raijada, 2013, A step toward development of printable dosage forms for poorly soluble drugs, J. Pharm. Sci., 102, 3694, 10.1002/jps.23678
Palo, 2015, Improvement of dissolution rate of indomethacin by inkjet printing, Eur. J. Pharm. Sci., 75, 91, 10.1016/j.ejps.2015.03.009
Speer, 2018, Novel dissolution method for oral film preparations with modified release properties, AAPS PharmSciTech, 20, 7, 10.1208/s12249-018-1255-1
Eguchi, 2017, Electrochemical polymerization of 4,4-dimethyl-2,2′-bithiophene in concentrated polymer liquid crystal solution, J. Mater. Sci. Chem. Eng., 5, 64
Yang, 2015, Synthesis and investigation of water-soluble anticoagulant warfarin/ferulic acid grafted rare earth oxide nanoparticle materials, RSC Adv., 5, 17824, 10.1039/C4RA14633F
Parfenyuk, 2017, Development of novel warfarin-silica composite for controlled drug release, Pharm. Res., 34, 825, 10.1007/s11095-017-2111-9
Reddy, 2013, Development and characterization of hydroxy propyl cellulose/poly(vinyl alcohol) blends and their physico-chemical studies, Indian J. Adv. Chem. Sci., 2, 38
World Health Organization (2012). Development of Pediatric Medicines: Points to Consider in Pharmaceutical Development (Working Document QAS/08.257/Rev.3), World Health Organization.
European Medicines Agency (2018). ICH Guideline Q3C (R7) on Impurities: Guideline for Residual Solvents Step 5, European Medicines Agency.