Leveraging a multivariate approach towards enhanced development of direct compression extended release tablets

Extended release formulations play a crucial role in the pharmaceutical industry by maintaining steady plasma levels, reducing side effects, and improving therapeutic efficiency and compliance. One commonly used method to develop extended release formulations is direct compression, which offers several advantages, such as simplicity, time savings, and cost-effectiveness. However, successful direct compression-based extended release formulations require careful assessment and an understanding of the excipients’ attributes. The scope of this work is the characterization of the compaction behavior of some matrix-forming agents and diluents for the development of extended release tablets. Fifteen excipients commonly used in extended release formulations were evaluated for physical, compaction and tablet properties. Powder properties (e.g., particle size, flow properties, bulk density) were evaluated and linked to the tablet’s mechanical properties in a fully integrated approach, and data were analyzed by constructing a principal component analysis (PCA). Significant variability was observed among the various excipients. The present work successfully demonstrates the applicability of PCA as an effective tool for comparative analysis, pattern and clustering recognition and correlations between excipients and their properties, facilitating the development and manufacturing of direct compressible extended release formulations.

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Materials

The materials (15) included in this study were purchased from or provided by BASF (Ludwigshafen, Germany), The Dow Chemical Company (Midland, MI, USA), Merck & Co. (Kenilworth, New Jersey, USA), JRS Pharma (Rosenberg, Baden-Wurttemberg, Germany), BENEO (Mannheim, Baden-Wurttemberg, Germany), Avesta Pharma Pvt. Ltd. (Mumbai, Maharashtra, India), Roquette (Lestrem, France), MEGGLE Pharma (Wasserburg am Inn, Germany) and UNDESA (Barcelona, Spain). Table 1 provides an overview of the raw materials. Chemical Abstracts Service (CAS) number and unique ingredient identifier (UNII) were used as identifiers linked to the substance’s molecular structure or descriptive information.

Table 1. Raw materials used in the study, their function and manufacturer.

Abbreviation	Excipient name	Commercial name	Function	CAS N.	UNII	Manufacturer
KL-SR	Acetate polyvinyl 80% PVP 20%	Kollidon® SR	Matrix former	9003-20-7 9003-39-8	32K497ZK2U	BASF
HPMCK4M	Hydroxypropyl methylcellulose	Methocel™ K4M Premium	Matrix former	9004-65-3	3NXW29V3WO	DuPont
HPMCK100	Hydroxypropyl methylcellulose	Methocel™ K100 Premium CR	Matrix former	9004-65-3	3NXW29V3WO	DuPont
PEO-N750	Poly(ethylene)oxide	POLYOX™ WSR N750	Matrix former	25322-68-3	4QIB4U4CQR	DuPont
PEO-1105	Poly(ethylene)oxide	POLYOX™ WSR 1105	Matrix former	25322-68-3	16P9295IIL	DuPont
PEO-303	Poly(ethylene)oxide	POLYOX™ WSR 303	Matrix former	25322-68-3	G3MS6M810Y	DuPont
PVA	Polyvinyl alcohol	Parteck® SRP80	Matrix former	9002-89-5	532B59J990	Merck & Co
RL	Lactose coprocessed	RetaLac®	Matrix former	5989-81-1 9004-65-3	EWQ57Q8I5X 39J80LT57T	MEGGLE
ADCP	Calcium hydrogen phosphate anhydrous	Emcompress® Anhydrous	Diluent	7757-93-9	L11K75P92J	JRS Pharma
G721	Isomalt	galenIQ™ 721	Diluent	64519-82-0	S870P55O2W	BENEO
TA-80	Lactose Monohydrate	Tablettose® 80	Diluent	64044-51-5	EWQ57Q8I5X	MEGGLE
MD-IT12	Maltodextrin	Glucidex® IT 12	Diluent	9050-36-6	7CVR7L4A2D	Roquette
MAN-400DC	Mannitol	Pearlitol® 400 DC	Diluent	69-65-8	3OWL53L36A	Roquette
PEG6000	Poly(ethylene glycol) 6000	Macrogol 6000	Diluent	25322-68-3	30IQX730WE	Avesta Pharma
SMCCHD90	Silicified Microcrystalline Cellulose	PROSOLV® SMCC HD90	Diluent	9004-34-6	OP1R32D61U	JRS Pharm
MgSt	Magnesium stearate	Kemilub EM-F-V	Lubricant	557- 04-0	70097M6I30	UNDESA

A.S. Sousa, J. Serra, C. Estevens, R. Costa, A.J. Ribeiro, Leveraging a multivariate approach towards enhanced development of direct compression extended release tablets, International Journal of Pharmaceutics, 2023, 123432, ISSN 0378-5173, https://doi.org/10.1016/j.ijpharm.2023.123432.