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

Heidi Öblom,Niklas Sandler,Maria Rautamo,Erica Sjöholm

doi:10.3390/pharmaceutics11070334

Heidi Öblom, Niklas Sandler + Show 2 more

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https://doi.org/10.3390/pharmaceutics11070334

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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.

Highlights

The lack of suitable dosage forms or doses for children is a common situation in hospital wards [1]
This study aims to compare the use of extrusion 3D printing (EXT) and inkjet printing (IJP) with the conventional manufacturing method for compounding oral powders in unit dose sachets (OPSs) to produce various doses of warfarin
A simple formulation consisting of the drug and hydroxypropyl cellulose (HPC) dissolved in a mixture of purified water and ethanol was chosen due to the excellent film-forming capacity of HPC, which resulted in clear, flexible films without the need of plasticizers

Summary

Introduction

The lack of suitable dosage forms or doses for children is a common situation in hospital wards [1]. A common way of tailoring the dose in hospital wards is by splitting the tablet into halves or quarters, which further may be crushed and dissolved or dispersed before administration if the patient is unable to swallow tablets or in cases where the drug is administered through a naso-gastric tube. An alternative to tablet splitting is compounding of oral liquids, capsules, or oral powders in unit dose sachets (OPS) at the hospital pharmacy [8]. Capsules, and segments of tablets are dissolved or dispersed in a liquid before administration or alternatively given with food. For many hospitalized children the medication is given through an enteral feeding tube, which require the drug to be in liquid form or formulated in such a way that it can be dissolved or dispersed prior to administration. The fact that some patients have fluid restrictions further affect the requirements for the administration of dosage forms

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