Combining experimental design and orthogonal projections to latent structures to study the influence of microcrystalline cellulose properties on roll compaction

• Published in: International journal of pharmaceutics Vol. 416; no. 1; pp. 110 - 119
• Main Authors: Dumarey, Melanie, Wikström, Håkan, Fransson, Magnus, Sparén, Anders, Tajarobi, Pirjo, Josefson, Mats, Trygg, Johan
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 15.09.2011; Elsevier
• Subjects: Biological and medical sciences; bulk density; cellulose; Cellulose - chemistry; compressibility; Drug Compounding - methods; Excipients - chemistry; Experimental design; General pharmacology; granules; heat; least squares; manufacturing; Medical sciences; Microcrystalline cellulose; Models, Statistical; Orthogonal projections to latent structures; Particle Size; pharmaceutical industry; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Porosity; Powders - chemistry; Principal component analysis; Research Design; Rheology - statistics & numerical data; Roll compaction; Tablet manufacturing; Tablets - chemistry; Technology, Pharmaceutical - methods; Technology, Pharmaceutical - statistics & numerical data; Tensile Strength; Experimental design; Microcrystalline cellulose; Roll compaction; Orthogonal projections to latent structures; Tablet manufacturing; Principal component analysis; Microcrystalline material; Pharmaceutical technology; Cellulose; Compaction; Preparation; Dosage form; Tablet; Manufacturing
• ISSN: 0378-5173; 1873-3476; 1873-3476
• DOI: 10.1016/j.ijpharm.2011.06.018

Roll compaction is gaining importance in pharmaceutical industry for the dry granulation of heat or moisture sensitive powder blends with poor flowing properties prior to tabletting. We studied the influence of microcrystalline cellulose (MCC) properties on the roll compaction process and the consecutive steps in tablet manufacturing. Four dissimilar MCC grades, selected by subjecting their physical characteristics to principal components analysis, and three speed ratios, i.e. the ratio of the feed screw speed and the roll speed of the roll compactor, were included in a full factorial design. Orthogonal projection to latent structures was then used to model the properties of the resulting roll compacted products (ribbons, granules and tablets) as a function of the physical MCC properties and the speed ratio. This modified version of partial least squares regression separates variation in the design correlated to the considered response from the variation orthogonal to that response. The contributions of the MCC properties and the speed ratio to the predictive and orthogonal components of the models were used to evaluate the effect of the design variation. The models indicated that several MCC properties, e.g. bulk density and compressibility, affected all granule and tablet properties, but only one studied ribbon property: porosity. After roll compaction, Ceolus KG 1000 resulted in tablets with obvious higher tensile strength and lower disintegration time compared to the other MCC grades. This study confirmed that the particle size increase caused by roll compaction is highly responsible for the tensile strength decrease of the tablets.