Solid Formulation Development Using Melt-based 3D Printing Technologies – article by Merck

Three-dimensional (3D) printing is a powerful technology that has wide-ranging applications, including many in the pharmaceutical industry. 3D printing offers the potential to produce medications tailored to the needs of patients and dosage forms in various shapes, sizes, and textures with different release profiles that can be difficult to produce using conventional techniques.¹

For the production of pharmaceutical dosage forms, 3D printing can be applied to powder-based, liquid-based, and extrusion-based systems. For powder-based systems, drop-on-powder (DOP) and selective laser sintering (SLS) technologies can be used while for liquid-based systems, drop-on-drop deposition (DOD) and stereolithography (SLA) can be applied. Extrusion-based systems include for example fused-deposition modeling (FDM) and melt-drop deposition (MED^®).

This technical article by Merck shows how 3D printing can overcome challenges during formulation development, with a focus on enhancement of bioavailability of active pharmaceutical ingredients (APIs) in solid dispersions.

OVERVIEW OF HOT MELT EXTRUSION AND THE 3D PRINTING PROCESS

The 3D printing process for pharmaceuticals takes place in two steps:

1. Choose a polymer that is compatible with the API and that is suitable for printing
2. Print the API, e.g. using melt drop deposition. For some approaches, the manufacturing of an intermediate, such as strands manufactured using HME, is necessary.

CHOOSING AN HME POLYMER FOR 3D PRINTING

In choosing a polymer for HME for 3D printing, it’s important to consider how the shear rate impacts viscosity. Ideally, the viscosity should decrease with an increasing shear rate (Figure 1). This is essential when it comes to processing material through very small nozzles to enable an efficient downstream process.

MELT DROP DEPOSITION

In the melt drop deposition process for solid dosage forms, which is sometimes also referred to as melt extrusion deposition, the polymer is melted in a heated plasticizer barrel in which a screw rotates and transports the material to the nozzle tip. When the polymer melt reaches the polymer reservoir, pressure is applied via translational movement of the screw, and droplets are discharged via a piezo actuator which can operate at a very high frequency of up to 250 hertz (Figure 2).

SEM images of the top and side surfaces of 3D printed tablets and strands show high homogeneity of this deposition process. A detailed view of the strands shows the individual drops that were deposited (Figure 3).

The infill volume can be varied to individually adjust the porosity of the tablets (Figure 4). This allows us to modify and match the targeted release kinetics.

This system was highly reproducible for tablet production. Figure 5 shows the mass distribution for the Parteck^® MXP excipient placebo tablets and those containing 10% caffeine. A comparison of the mass versus the inflow volume showed relatively lower homogeneity for the formulation with caffeine, but still within the required limits. The mechanical stability of the tablets was also a key consideration. Diametral compression was assessed with a texture analyzer and showed that 3D printed tablets based on Parteck^® MXP excipient provided high mechanical strength even at low infill volumes (Figure 6). The high mechanical strength also translates into low friability values over the entire process range.

Read the full article here

Source: Merck website, article “Solid Formulation Development Using Melt-based 3D Printing Technologies”

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