Track: Formulation and Delivery - Chemical - Formulation - Oral - Immediate Release
Category: Poster Abstract
3D Powder Bed Printing of Lactose Tablets
Purpose: The Food and Drug Agency (FDA) has provided with their Pharma 4.0 vision a clear path forward regarding Pharmacy on Demand or so-called personalized medicine. In this context enabling personalized medicine to accelerating the drug development pathway, 3D printing (3DP) offers huge potential benefits in pharmaceutical manufacturing1. To embrace this new world of opportunities, we need a thorough understanding of the materials, processes and techniques involved. Powder bed printing is one of the techniques most commonly explored in pharmaceutics. In powder bed or drop on solid printing a thin layer of powder is placed on the platform. The nozzle will precisely wet the powder by jetting small droplets of the ink (water/ethanol) into the powder. The wetted powder will solidify and a new layer of powder will be dispositioned onto the bed. This layer will again be wetted and this process will be repeated until the tablet is finalized (Figure 1). In this study we investigate the benefits of powder based 3D printing by utilizing a base formulation of lactose monohydrate and pregelatinized starch. Working with TNO (The Netherlands), DFE Pharma tested over 20 lactose grades in order to create a formulation which can be used effectively in the powder bed 3D printing. The primary objective of this research was developing lactose blends with sufficient flow, wetting and binding. Methods: To determine the ability of a lactose monohydrate and pregelatinized starch blend (90:10 w/w) to be successful, the mixture was first characterized on flowability (shear cell) and wettability (drop shape analyzer). After the physical chemical analysis the formulation was printed into a 9 mm tablet of 2.8 mm height by means of a PBP Next printer. A specific grade of lactose monohydrate and pregelatinized starch were mixed manual and printed with a PBP Next printer with a Lee valve INKA2476210H (0.178mm). The powder blend was automatically dispersed from a hopper onto the powder platform and automatically rolled out with a roller on a printer. The ink (95% water and 5% ethanol v/v) was sprayed on the powder bed with print settings as indicated in Figure 2. The powder deposition and solution spraying was repeated 7 times in order to create a flat tablet with a diameter of 9 mm and a height of 2.8 mm. Tablets were removed from the powder bed and dried in an oven overnight at 50°C. Tablets were after the drying stage characterized on hardness (n=10 tablets), friability (n=3 tablets) and disintegration (n=3 tablets) Results: Powder formulations having a flow function coefficient (FFC) well above 10, such as the selected lactose/pregelatinized starch mix with a FFC of 21, are indicated as free flowing. The bulk density of the powder bed has a high impact on the density of the tablet, as there is no further compaction step. A higher density, such as 0.7 g/ml of the current blend is preferred because it will result in a stronger tablet. To show the relationship between line spacing and wetting, an experiment was performed to proof that a high contact angle (68°) and fast penetration time (0.2 sec) should result in a quick uptake of the ink and consequently a smooth surface. Despite the variation in line spacing (0.2 up to 0.6 mm), Figure 3 shows that the surface of the powder remains smooth and no balling was seen. However, first squares are overwetted and the final three squares have insufficiently consolidated. This means that the optimal linespacing is between 0.34 and 0.45 mm. The powder characterization clearly indicates that the lactose blend is suitable for printing due to its good flow and density properties. This was confirmed by the hardness and the indicative friability of the resulting tablets, being respectively 61N and 1.2% w/w (Figure 2 shows a picture of the tablet). Although this friability is still above the desired value of 1% w/w, we are confident that further optimization will result in an acceptable friability. The disintegration time of the tablets was 52 seconds, which is common for IR powder bed tablets. Conclusion: The selection of the right functional excipients is vital to obtain 3D printed tablets that are approaching the industry standard. This study clearly shows the benefit of powder bed printed tablets with a blend of lactose monohydrate and pregelatinized starch as main carrier system. This research also indicates how the tablet hardness and disintegration time (not shown) can be controlled by managing the printer settings, which is desirable in the route towards personalized medication for patients.
Trenfield, S. Awad, A. Goyanes, A. Gaisford, S. and Basit, A. 3D Printing Pharmaceuticals: Drug Development to Frontline Care, Trends in Pharmacological Sciences, Vol. 39, No. 5, 440-451 (2018)