Direct Powder Extrusion of Paracetamol Loaded Mixtures for 3D Printed Pharmaceutics for Personalized Medicine via Low Temperature Thermal Processing.

Xabier Mendibil,Nerea Uranga,Gaizka Tena,Jesús Alonso,Alaine Duque,Miguel Ángel Campanero

doi:10.3390/pharmaceutics13060907

Abstract

Three-dimensional printed drug development is nowadays an active area in the pharmaceutical industry, where the search for an appropriate edible carrier that permits the thermal processing of the mixture at temperature levels that are safe for the drug is an important field of study. Here, potato starch and hydroxypropyl cellulose based mixtures loaded with paracetamol up to 50% in weight were processed by hot melt extrusion at 85 °C to test their suitability to be thermally processed. The extruded mixtures were tested by liquid chromatography to analyze their release curves and were thermally characterized. The drug recovery was observed to be highly dependent on the initial moisture level of the mixture, the samples being prepared with an addition of water at a ratio of 3% in weight proportional to the starch amount, highly soluble and easy to extrude. The release curves showed a slow and steady drug liberation compared to a commercially available paracetamol tablet, reaching the 100% of recovery at 60 min. The samples aged for 6 weeks showed slower drug release curves compared to fresh samples, this effect being attributable to the loss of moisture. The paracetamol loaded mixture in powder form was used to print pills with different sizes and geometries in a fused deposition modelling three-dimensional printer modified with a commercially available powder extrusion head, showing the potential of this formulation for use in personalized medicine.

Highlights

The present paper studies the suitability of different formulations, based on starch and Hydroxypropyl Cellulose (HPC) with different proportions of acetaminophen, to be processed at a low temperature by hot melt extrusion, searching the compliance to be printed in an Fused deposition modelling (FDM)
Starch and HPC based mixtures loaded with paracetamol were processed by hot melt extrusion
The samples prepared with the addition of water at 3% wt ratio proportional to the starch amount turned out to be extrudable at low temperature (85 ◦ C) and highly soluble, yielding recovery rates up to 100% at 60 min in HCl 0.1 N at 37 ◦ C

Summary

Introduction

The use of 3D printing allows the personalization of the oral forms (3DP pills) to improve adherence, but to customize the drug dosage, which is of great interest in the definition of the prescription for adults and is critical in pediatrics [10,11,12,13]

Methods

Results

Conclusion