Off-the-shelf medication transformed: Custom-dosed metoprolol tartrate tablets via semisolid extrusion additive manufacturing and the perception of this technique in a hospital context

Abstract

Pharmacies are currently unable to stock proper oral dosage forms for pediatric populations. This leads to manipulation of medications or the need to compound specialized medications, which can be a time-consuming process. Using Semisolid Extrusion (SSE) additive manufacturing (AM), specialized medications can be produced in an expedited process from off-the shelf medication in a hospital or outpatient pharmacy setting. In this study, tablets with a desired dose of 5 mg of metoprolol tartrate derived from commercial Seloken™ 50 mg tablets were 3D printed in a hospital setting. Validation testing was done on five batches, highlighting tablets with a high uniformity in mass and dimension, drug content, acceptable microbial assays, and prolonged release during in-vitro analysis. The average drug content found for the tablets was within ±6% of 5 mg for all batches produced. Comparisons were done between the SSE tablets and capsules produced in an external compounding facility, highlighting several positive aspects of SSE-produced tablets beyond simply shortening the production timeline. The SSE tablets printed in this study are characterized by their smaller size, enhanced prolonged release properties, and more uniform drug content across the tested samples. Additionally, interviews with pharmaceutical professionals were conducted to determine the positive aspects of SSE and further improvements to bring this technique as seamlessly as possible into the pharmacy. This study underscores the feasibility of employing SSE in the production of specialized medications within a hospital environment. Furthermore, it highlights the methodological advantages SSE offers over existing production standards, demonstrating its potential to improve pharmaceutical manufacturing in healthcare settings.

Keywords: 3D printing; Additive manufacturing; Dose modification; Semisolid Extrusion.

Graphical abstract

Fig. 1

Linear correlation for drug content of tablets with varying STL dimensions for the formulation prepared in this study (x̅ ± s, n ≥ 5).

Fig. 2

Mass results of five batches of printed tablets (x̅ ± s, n ≥ 27) as well as the ECF prepared capsules (x̅ ± s, n = 100).

Fig. 3

Image of tablets post-drying.

Fig. 4

DSC results for SSE tablets, ECF capsules, and Seloken™ 50 mg tablets.

Fig. 5

Drug content for tablets tested from the five batches made in the study and the ECF capsules.

Fig. 6

In-vitro drug release, with A) Average Amount of API Released (%) for SSE Tablets, B) Average amount of API Released (%) for ECF Capsules; x̅ ± s, n = 3.

Fig. 7

A) Current order process, where an order is placed, then the ECF compounds the capsules, and sends them to the hospital or pharmacy for the patient, with the process taking five days on average, B) Proposed order process, where medication is ordered, printed in the hospital pharmacy, and dispensed out from the centralized printing hub.