Towards Printed Pediatric Medicines in Hospital Pharmacies: Comparison of 2D and 3D-Printed Orodispersible Warfarin Films with Conventional Oral Powders in Unit Dose Sachets

Abstract

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.

A Focus Group Study about Oral Drug Administration Practices at Hospital Wards—Aspects to Consider in Drug Development of Age-Appropriate Formulations for Children

“…Investigations into novel oral dosage forms for children have indicated that formulations such as orodispersible mini-tablets or films are promising options in pediatric drug development, enabling personalized and flexible drug administration [7,32]. Dose titrations of enalapril maleate doses in the range of 0.025-4 mg were manageable with orodispersible mini-tablets of two different strengths (0.25 and 1 mg, respectively), facilitating flexible dosing for different patient groups [32].…”

“…The production of orodispersible films by means of 2D or 3D printing is considered a possibility for on-demand manufacturing of patient-specific doses [33,34]. Recently, two different printing technologies were used to produce orodispersible films containing four different commonly used pediatric doses of warfarin sodium [7]. It was shown that content uniformity and dose accuracy of the printed orodispersible films were at least equally good as for dose powders currently used for pediatrics.…”

“…It was shown that content uniformity and dose accuracy of the printed orodispersible films were at least equally good as for dose powders currently used for pediatrics. Both orodispersible mini-tablets and films dispersed in water were also suitable for administration through a nasogastric tube without causing blockage of the tube [7,32]. As enteral feeding tubes are widely used in the hospital setting, it is desirable that tests mimicking administration through feeding tubes for children are performed during drug development.…”

“…Recommendations considering the risk of physical blockage of the feeding tube as well as the chemical compatibility of a drug product with the tube material have been published by European Medicines Agency (EMA) in a guideline on pharmaceutical development of medicines for children [6]. Such events would affect the administered drug amount; however, potential drug loss can be shown by mimicking drug administration through enteral feeding tubes for children [5,7].…”

3D Printing of Pharmaceuticals and Drug Delivery Devices

“…In order to provide additional information about the dosage form and to reduce the errors that occur in the administration of medication a Quick Response (QR) code was printed onto the ODFs using IJP. The study demonstrated how printing technologies are promising techniques for the development of patient-specific dosage forms [19].…”