A Quantitative Correlation of the Effect of Density Distributions in Roller-Compacted Ribbons on the Mechanical Properties of Tablets Using Ultrasonics and X-ray Tomography

Abstract

Enabling the paradigm of quality by design requires the ability to quantitatively correlate material properties and process variables to measureable product performance attributes. In this study, we show how heterogeneities in compacted ribbon densities quantitatively correlate to tablet mechanical properties. These density variations, which have been purposely modulated by internal and external lubrications, are characterized longitudinally and transversally by nondestructive ultrasonic and X-ray micro-computed tomography measurements. Subsequently, different transversal regions of the compacted ribbon are milled under the same conditions, and granules with nominally the same particle size distribution are utilized to manufacture cylindrical tablets, whose mechanical properties are further analyzed by ultrasonic measurements. We consider three different ribbon conditions: no lubrication (case 1); lubricated powder (case 2); and lubricated tooling (hopper, side sealing plates, feed screws, and rolls) (case 3). This study quantitatively reveals that variation in local densities in ribbons (for case 1) and process conditions (i.e., internal case 2 and external lubrication case 3) during roller compaction significantly affect the mechanical properties of tablets even for granules with the same particle size distribution. For case 1, the mechanical properties of tablets depend on the spatial location where granules are produced. For cases 2 and 3, the ribbon density homogeneity was improved by the use of a lubricant. It is demonstrated that the mechanical performances of tablets are decreased due to applied lubricant and work-hardening phenomenon. Moreover, we extended our study to correlate the speed of sound to the tensile strength of the tablet. It is found that the speed of sound increases with the tensile strength for the tested tablets.

Evaluation of Three Approaches for Real-Time Monitoring of Roller Compaction with Near-Infrared Spectroscopy

“…Recent studies demonstrate that the compression pressure in the middle of ribbon width is higher than that at the edges (9). The density variations in roller compacts have been recently investigated with ultrasonic testing and X-ray tomography (10). A recent study demonstrates the density distribution along the ribbon by analyzing off-line images of MCC ribbons obtained via near-infrared (NIR) chemical imaging (11).…”

Critical Review on Engineering Mechanical Quality of Green Compacts using Powder Properties

“…In addition, Glass and Ewsuk (1995) used ultrasound to determine relative density of alumina compact. Akseli et al (2011) used both ultrasound and X-ray CT to determine density distribution of ribbon compacted microcrystalline cellulose in investigation of mechanical properties. They showed that both methods have resolution to distinguish spatially distributed density in compacts.…”

Effect of Reprocessing and Excipient Characteristics on Ibuprofen Tablet Properties

“…These tablets were also analyzed for tensile strength determined from the crushing strength data (UK200, VanKel, Manasquan, USA) as reported previously [9]. Tablets were then passed through an oscillating granulator (Riddhi Pharma Machinery, India) fitted with a # 20 sieve (840 µm pore size), analyzed for particle size, porosity and densities.…”

“…This granulation is desirable for heat or moisture sensitive drugs [8]. The characteristics of the granules produced by direct compression and wet granulation influence compact hardness, disintegration and drug dissolution [9,10]. If hydrophobic drugs are used, hydrophilic liquids can be added during wet granulation to wet a powder blend to facilitate tablet disintegration and drug dissolution [11][12][13][14] On the other hand, sometimes formulation scientists have to face problems related with manufacture of compacts due to changes in crystallinity, porosity, hygrospicity, particle size which have a deleterious effect on critical manufacturing properties such as flow, compressibility and compactibility of excipients or drug:excipients mixtures.…”