Prediction of Solid-State Form of SLS 3D Printed Medicines Using NIR and Raman Spectroscopy.

Patricija Januskaite,Simon Gaisford,Sarah J. Trenfield,Martin Rowland,David Wilsdon,Abdul W. Basit,Alvaro Goyanes

doi:10.3390/pharmaceutics14030589

Abstract

Selective laser sintering (SLS) 3D printing is capable of revolutionising pharmaceutical manufacturing, by producing amorphous solid dispersions in a one-step manufacturing process. Here, 3D-printed formulations loaded with a model BCS class II drug (20% w/w itraconazole) and three grades of hydroxypropyl cellulose (HPC) polymer (-SSL, -SL and -L) were produced using SLS 3D printing. Interestingly, the polymers with higher molecular weights (HPC-L and -SL) were found to undergo a uniform sintering process, attributed to the better powder flow characteristics, compared with the lower molecular weight grade (HPC-SSL). XRPD analyses found that the SLS 3D printing process resulted in amorphous conversion of itraconazole for all three polymers, with HPC-SSL retaining a small amount of crystallinity on the drug product surface. The use of process analytical technologies (PAT), including near infrared (NIR) and Raman spectroscopy, was evaluated, to predict the amorphous content, qualitatively and quantitatively, within itraconazole-loaded formulations. Calibration models were developed using partial least squares (PLS) regression, which successfully predicted amorphous content across the range of 0–20% w/w. The models demonstrated excellent linearity (R2 = 0.998 and 0.998) and accuracy (RMSEP = 1.04% and 0.63%) for NIR and Raman spectroscopy models, respectively. Overall, this article demonstrates the feasibility of SLS 3D printing to produce solid dispersions containing a BCS II drug, and the potential for NIR and Raman spectroscopy to quantify amorphous content as a non-destructive quality control measure at the point-of-care.

Highlights

The discs and printlets produced with the higher polymer molecular weights (HPC-L and hydroxypropyl cellulose (HPC)-SL) displayed a more uniform sintering on the formulation surface for both discs and printlets
This paper demonstrates the ability of Selective laser sintering (SLS) 3DP to create amorphous solid dispersions of a BCS Class II drug with three different HPC polymer grades (HPC-L, HPC-SL, and HPC-SSL)
The polymers with higher molecular weights (HPC-L and -SL) underwent a uniform sintering process, attributed to the increased particle size, and, had improved flow characteristics compared with the lower molecular weight grade (HPC-SSL), which demonstrated craters and defects on the formulation surface

Summary

Introduction

Administered drug products are by far the preferred form of medication, recognised as being low cost, simple to administer, and having a high acceptability in patients [1]. Around 40% of these products possess low water solubility and poor bioavailability, alongside a staggering 90% of new molecules, resulting in a high failure rate during drug development [2]. Due to these statistics, using enabling technologies to formulate drugs in the amorphous form as solid amorphous dispersions (SADs) has been of major interest in the pharmaceutical field in recent years.

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