Evaluation of lactose based 3D powder bed printed pharmaceutical drug product tablets

It is key to understand powder blend characteristics in relation to tablet characteristics when using pharmaceutical 3D printing, in order to obtain 3D powder bed printed tablets that comply with the pharmaceutical specifications. There is limited literature available on excipient selection for 3D printing, even though the only marketed 3D printed drug is prepared with powder bed printing.

Highlights

• A lactose monohydrate binder blend is preferred for 3D powder bed printing.

• Wettability is related to the particle size distribution of the blend.

• A hydrophilic and hydrophobic API was successfully formulated into a printed tablet.

• The impact of pre-blend/print settings on tablet hardness and dissolution was studied.

• Optimizing the pre-blend and print settings have to be in conjunction for 3D printing.

In this study, the impact of different particle size distributions of lactose-starch base formulations on key critical material attributes such as wettability, consolidation and flowability was studied. It was found that fewer fines in the particle size of the blend is beneficial for a fast penetration time of the ink (liquid) into the powder bed. The impact of varying the print settings or binder type on primary tablet properties such as hardness and dissolution was studied using formulations with Acetaminophen or Diclofenac Sodium. It was found that optimizing the base formulation and print settings have to be in conjunction as they are closely related. This study shows in detail how hydrophilic/hydrophobic API’s can be successfully formulated into 3D printed tablets taking into account the formulation considerations as described.

Continue reading here – (Open access – Journal Pre-Proof): K.A. van den Heuvel, M.T.W. de Wit and B.H.J. Dickhoff, Evaluation of lactose based 3D powder bed printed pharmaceutical drug product tablets, Powder Technology (2021), https://doi.org/10.1016/j.powtec.2021.05.050

Materials
The materials used are sieved lactose monohydrate, milled and classified lactose monohydrate, fully pregelatinized potato starch, partly pregelatinized maize starch and sodium starch glycolate (Primojel®, DFE Pharma, Germany), Povidone (Duchefa Farma, The Netherlands), Diclofenac Sodium as hydrophobic model compound with a particle size of x10 = 1.8, x50 = 17.4 and x90 = 76.8 μm (Fagron, The Netherlands) and Acetaminophen fine powder as hydrophilic model compound with a particle size of x10 = 4.3, x50 = 22.1 and x90 = 82.3 μm (Mallinckrodt, Raleigh, NC, USA). The hydrophilic and hydrophobic model drug compound were selected as they have a different wettability and should therefore behave differently in the 3D powder bed system

Conclusions
Lactose monohydrate is a suitable functional filler for 3D powder bed tablet printing when combined with an appropriate binder. The fines (as measured by the x10) of the lactose starch base formulation had a significant impact on the wettability and flowability of the blend and optimization is required for each type of formulation. Both powder mixtures 1 and 2 were suitable for 3D printing, however one grade was more suited for an API with challenging flow where the other provides a solution in poor wettability of the API.

This study shows that a hydrophilic API has been successfully formulated with a base formulation based on lactose, fully pregelatinized starch and Primojel®. The type and amount of binder required showed a clear relation to the amount of printing liquid used in the production of the tablets. Thereby giving a formulation design space in which the optimal balance between hardness and disintegration can be found. The hardness-disintegration balance is impacted by parameters such as amount of print liquid and droplet size. Therefore, these will be an important topic for future research.

A successful formulation for the hydrophobic model compound was achieved using a base formulation of lactose/partly gelatinized starch. The use of partly gelatinized starch had a superior balance between tablet hardness and disintegration in 3D printed tablets compared to using fully pregelatinized starch. This will be optimized in future work by varying the binder level and the addition of a disintegrant.