A QbD Approach for Evaluating the Effect of Selective Laser Sintering Parameters on Printability and Properties of Solid Oral Forms.

Yanis A Gueche,Noelia M Sanchez-Ballester,Ian Soulairol,Bernard Bataille,Jean-Christophe Rossi,Adrien Aubert

doi:10.3390/pharmaceutics13101701

Abstract

The aim of this work was to investigate the effect of process parameters on the printability of a formulation containing copovidone and paracetamol, and on the properties of solid oral forms 3D-printed through selective laser sintering. Firstly, the influence of the heating temperature was evaluated individually, and it was revealed that this parameter was critical for printability, as a sufficiently high temperature (100 °C) is necessary to avoid curling. Secondly, the effects of laser power, scan speed, and layer thickness were determined using a Box–Behnken design. The measured responses, printing yield, height, weight, hardness, disintegration time, and percentage of drug release at 10 min showed the following ranges of values: 55.6–100%, 2.92–3.96 mm, 98.2–187.2 mg, 9.2–83.4 N, 9.7–997.7 s, and 25.8–99.9%, respectively. Analysis of variance (ANOVA) proved that the generated quadratic models and the effect of the three–process parameters were significant (p < 0.05). Yield improved at high laser power, low scan speed, and increased layer thickness. Height was proportional to laser power, and inversely proportional to scan speed and layer thickness. Variations in the other responses were related to the porosity of the SOFs, which were dependent on the value of energy density. Low laser power, fast scan speed, and high layer thickness values favored a lower energy density, resulting in low weight and hardness, rapid disintegration, and a high percentage of drug release at 10 min. Finally, an optimization was performed, and an additional experiment validated the model. In conclusion, by applying a Quality by Design approach, this study demonstrates that process parameters are critical for printability, but also offer a way to personalize the properties of the SOFs.

Highlights

This study study demonstrates demonstrates that that different different processing processing parameters parameters of of selective selective laser laser sinsinThis tering influence tering influence the the printability and properties of solid oral forms printed with copovidone and paracetamol
The first part of this work highlights the importance of an optimal heating temperature to prevent curling of the sintered layers, and to guarantee printability of the formulation
Second part of this work demonstrates that laser power, scan speed, and layer thickness

Summary

Introduction

Three-dimensional printing, known as additive manufacturing, is a versatile technology that enables the production of devices with various applications [1]. This stateof-the-art technology occupies an important place in society, and has proved to be helpful and efficient on several occasions [2]. During the 2019 coronavirus disease pandemic (COVID-19), 3D printing provided a quick and easy solution to the shortage of protective equipment (such as masks and face shields) and medical instruments (ventilator valves) [3,4]. 3D printing is applied in dentistry, medical devices, and organ and tissue transplantation, and in the fabrication of solid oral forms, usually called “printlets” [5]. 3D printing is applied in dentistry, medical devices, and organ and tissue transplantation, and in the fabrication of solid oral forms, usually called “printlets” [5]. 4.0/).

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