Screening pharmaceutical excipient powders for use in commercial 3D binder jetting printers

Binder jetting is an additive manufacturing technique that creates three-dimensional constructs from a powder feedstock. It is used by several industries, including pharmaceuticals. This additive approach to manufacture provides several functional benefits that are not easily achievable using conventional manufacturing methods. There is currently only limited publicly available knowledge that details the requirements of an effective binder jetting powder. Specifically in the pharmaceutical industry, since the 2015 release of Spritam®, a binder-jetted tablet containing levetiracetam, no new pharmaceutical tablets have been produced using such methods.

 

Highlights

• Screening of pharmaceutical excipient powders for use in Binder Jetting process.

• Printable microcrystalline cellulose formulation developed.

• Various dosage shapes printed using pharmaceutical excipients.

• Particle engineering can tune flow and wetting properties to enhance printability.

There appears to be gap in powder technology expertise and the development of 3D printing processes. Our goal is to enhance our knowledge in terms of powder flow, powder wetting and powder binding to link particles with process and build the capability to create a greater range of powders suitable to be binder-jetted into new products. After initially screening several standard pharmaceutical excipient powders for their relevant properties, two candidates showed best fit potential for use in binder jetting, specifically microcrystalline cellulose (Pharmacel 101 and 102) and lactose (Lactohale 200). Using simple formulations of these pharmaceutical excipient powders as a model, we analysed for printability and powder performance using a range of quantitative parameters including dimensional accuracy, construct hardness, friability, porosity and surface finish. In general, formulations of these powders showed good printability, but some powder blends produced constructs with more obvious manufacturing imperfections. Several routes to improve the printability of these pharmaceutical powders are proposed for future works. Ultimately, this work provides a fundamental basis to start to quantitatively assess the potential of standard pharmaceutical excipient powders in binder jetting printers using powder characterisation techniques and print quality outcomes. Continue reading 

Table 1. Candidate powders evaluated for binder jetting in a Projet CJP 460Plus printer.

Powder Trade Name	Powder Generic Name	Manufacturer	Batch	d10	d50	d90
Calcium sulfate dihydrate	Set gypsum	Sigma Aldrich	BCBV1390	7	18	46
Calcium sulfate anhydrous	–	Sigma Aldrich	MKBW9429V	3	9	23
Calcium sulfate hemihydrate	Plaster of Paris	Sigma Aldrich	BCBV7581	5	17	62
Hydroxyapatite	–	Sigma Aldrich	BCBZ3280	3	7	15
β-tricalcium phosphate	–	Sigma Aldrich	BCBS4390V	3	7	17
Methocel E5	HPMC E5	Dow Chemical	VJ27012N23	24	51	107
Methocel E6	HPMC E6	Dow Chemical	QC27012402	24	49	127
Methocel K100	HPMC K100	Dow Chemical	TK06012N21	20	51	119
Methocel K4M	HPMC K4M	Dow Chemical	TD02012N12	23	62	186
Methocel K3	HPMC K3	Dow Chemical	TE18012N22	19	56	160
Salicylic Acid	–	Merck KGaA	F1591335	9	18	36
Croscarmellose sodium	–	DFE Pharma	Not available*	19	31	47
Sigmacell Cellulose	Cellulose	Sigma Aldrich	SLBN4490V	10	20	36
Avicel PH101	MCC 101	FMC Corp	BCBQ8403V	24	55	103
Pharmacel 101	MCC 101	DFE Pharma	765	25	60	120
Pharmacel 102	MCC 102	DFE Pharma	772	31	86	172
Lactopress anhydrous lactose	Lactose	DFE Pharma	956	3	20	70
Lactochem extra fine lactose	Lactose	DFE Pharma	974	3	20	50
Lactochem fine lactose	Lactose	DFE Pharma	752	3	15	40
Pharmatose 350 M	Lactose	DFE Pharma	689	4	30	80
Pharmatose 450 M	Lactose	DFE Pharma	105	3	20	50
Lactohale 200	Lactose	DFE Pharma	395	18	65	114
Pharmatose 130 M	Lactose	DFE Pharma	Not available*	16	85	196
20:80 VA64-Pharmacel 102	–	BASF-DFE Pharma	Not applicable**	27	73	150
20:80 VA64-Pharmacel 101	–	BASF-DFE Pharma	Not applicable**	21	54	105
20:80 VA64-Lactohale 200	–	BASF-DFE Pharma	Not applicable**	27	71	119
0.5:9.0:90.5 MgSt-VA64-Lactohale 200	–	Honeywell-BASF-DFE Pharma	Not applicable**	24	70	119

by A. Antic, J. Zhang, N. Amini, D.A.V. Morton, K.P. Hapgood, Screening pharmaceutical excipient powders for use in commercial 3D binder jetting printers, Advanced Powder Technology, 2021,ISSN 0921-8831, https://doi.org/10.1016/j.apt.2021.05.014. (https://www.sciencedirect.com/science/article/pii/S0921883121002387)