Embedded 3D Printing of Novel Bespoke Soft Dosage Form Concept for Pediatrics.

Katarzyna Rycerz,Katarzyna Rycerz,Mohamed A Alhnan,Marta Czapiewska,Krzysztof Adam Stepien,Rober Habashy,Basel T Arafat,Abdullah Isreb,Marta Czapiewska,Marta Czapiewska,Krzysztof Adam Stepien,Matthew Peak

doi:10.3390/pharmaceutics11120630

Abstract

Embedded three-dimensional printing (e-3DP) is an emerging method for additive manufacturing where semi-solid materials are extruded within a solidifying liquid matrix. Here, we present the first example of employing e-3DP in the pharmaceutical field and demonstrate the fabrication of bespoke chewable dosage forms with dual drug loading for potential use in pediatrics. LegoTM-like chewable bricks made of edible soft material (gelatin-based matrix) were produced by directly extruding novel printing patterns of model drug ink (embedded phase) into a liquid gelatin-based matrix (embedding phase) at an elevated temperature (70 °C) to then solidify at room temperature. Dose titration of the two model drugs (paracetamol and ibuprofen) was possible by using specially designed printing patterns of the embedded phase to produce varying doses. A linearity [R2 = 0.9804 (paracetamol) and 0.9976 (ibuprofen)] was achieved between percentage of completion of printing patterns and achieved doses using a multi-step method. The impact of embedded phase rheological behavior, the printing speed and the needle size of the embedded phase were examined. Owning to their appearance, modular nature, ease of personalizing dose and geometry, and tailoring and potential inclusion of various materials, this new dosage form concept holds a substantial promise for novel dosage forms in pediatrics.

Highlights

With increasing regulatory incentives for pediatric formulation development and focus in delivering patient-centred health care, developing age-appropriate formulations is gaining increased interest [1] from the pharmaceutical sector
E-3DP enabled the encapsulation of model drugs in pre-specified shapes into an embedding material
We adapted pharmaceutical materials to match the technical needs of Embedded 3D printing (e-3DP), which often requires the use of heat- or UV light-curable materials [29,30] to increase the rigidity of the embedding phase to solid or semi-solid states

Summary

Introduction

With increasing regulatory incentives for pediatric formulation development and focus in delivering patient-centred health care, developing age-appropriate formulations is gaining increased interest [1] from the pharmaceutical sector. There have been increasing efforts to provide high-quality, effective, and safe formulations for children [2]. The use of unlicensed and off-label medicines in pediatrics is extensive [3]. A lack of age-appropriate formulations for children means that available medicines are frequently modified to achieve an intended dose and/or administration to the child [3]. Tablets may need to be split by healthcare professionals or families to achieve an intended dose, with the potential for significant under- or over-dosing [4,5]

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Conclusion