Compression Density as an Alternative to Identify an Optimal Moisture Content for High Shear Wet Granulation as an Initial Step for Spheronisation

Pellet production is a multi-step manufacturing process comprising granulation, extrusion and spheronisation. The first step represents a critical control point, since the quality of the granule mass highly influences subsequent process steps and, consequently, the quality of final pellets. The most important parameter of wet granulation is the liquid requirement, which can often only be quantitatively evaluated after further process steps. To identify an alternative for optimal liquid requirements, experiments were conducted with a formulation based on lactose and microcrystalline cellulose. Granules were analyzed with a Powder Vertical Shear Rig. We identified the compression density (ρ_press) as the said alternative, linking information from the powder material and the moisture content (R² = 0.995). We used ρ_press to successfully predict liquid requirements for unknown formulation compositions. By means of this prediction, pellets with high quality, regarding shape and size distribution, were produced by carrying out a multi-step manufacturing process. Furthermore, the applicability of ρ_press as an alternative quality parameter to other placebo formulations and to formulations containing active pharmaceutical ingredients (APIs) was demonstrated.

Download the full article as PDF here Compression Density as an Alternative to Identify an Optimal Moisture Content for High Shear Wet Granulation as an Initial Step for Spheronisation

or read it here

 

Materials

 

Material		Type	Abbreviation	Company
A	Lactose anhydrate	DuraLac® H	Lac H	Meggle, Wasserburg, Germany
		Pharmatose® DCL 21	Lac DCL 21	DMV International, Veghel, The Netherlands
	Lactose monohydrate	GranuLac® 70	Lac 70	Meggle, Wasserburg, Germany
		GranuLac® 200	Lac 200	Meggle, Wasserburg, Germany
		Pharmatose® 200M	Lac 200M	DFE Pharma, Goch, Germany
		SorboLac® 400	Lac 400	Meggle, Wasserburg, Germany
	Mannitol	D(-)-Mannitol	Man	Merck, Darmstadt, Germany
		PEARLITOL® 50 C	Man 50 C	Roquette Frères, Lestrem, France
B	Microcrystalline cellulose	Microcel® MC-101	MCC MC-101	Roquette Frères, Lestrem, France
		VIVAPUR® 101	MCC 101	JRS Pharma, Rosenberg, Germany
		VIVAPUR® 102	MCC 102	JRS Pharma, Rosenberg, Germany
		VIVAPUR® 105	MCC 105	JRS Pharma, Rosenberg, Germany
API	Active pharm. ingredient	Caffeine (pure)		Merck, Darmstadt, Germany
		(2.0 μm ± 0.4 μm; n = 17) *
		Ibuprofen 25		BASF, Ludwigshafen, Germany
		(52.4 μm ± 25.9 μm; n = 17)
		Ketoprofen		Hubei Xunda Pharmaceutical, Wuxue, China
		(2.8 μm ± 0.6 μm; n = 17)
		Paracetamol		Merck, Darmstadt, Germany
		(19.5 μm ± 15.6 μm; n = 48)

Following excipients are mentioned in the study: Duralac H, Pharmatose DCL 21, Granulac 70, Granulac 200, Pharmatose 200M, Sorbolac 400, Pearlitol 50C, Microcel MC-101,Vivapur 101, Vivapur 102, Vivapur 105

Ramm, S.; Fulek, R.; Eberle, V.A.; Kiera, C.; Odefey, U.; Pein-Hackelbusch, M. Compression Density as an Alternative to Identify an Optimal Moisture Content for High Shear Wet Granulation as an Initial Step for Spheronisation. Pharmaceutics 2022, 14, 2303. https://doi.org/10.3390/pharmaceutics14112303