Issue link: https://www.e-digitaleditions.com/i/446555
Tablets & Capsules January 2015 27 The ribbon's density is the most important quality attribute to control because it determines how well the granules flow and compact during tabletting. The parameters that can be adjusted to control the ribbon's physical properties are feeding speed, roller speed, roller gap, and roller pressure. In addition, one or both of the smooth-surface rollers can be replaced with knurled- surface rollers in order to decrease slippage of the powder as it enters the nip zone. A deep understanding of the roller compaction process is required to ensure consistent product quality and performance across a range of environments. In fact, one of the most important challenges of process scale-up and technology transfer is identifying the process parameters that will produce granules with consistent properties. Accurate measurement of ribbon density is critical to achieving that. Furthermore, because terahertz spectro - scopy correlates the properties of raw and in-process materials and process parameters to measurable product performance attributes, it jibes with the goals of Quality by Design. It can also serve as a Process Analytical Technology tool by offering fast, non-destructive, and real-time analysis of roller-compacted ribbons to provide process understanding and help ensure product quality. Roller-compacted ribbons are inherently porous and can be characterized by apparent density, solid fraction, and percentage porosity (Table 1). There are several ways to measure the envelope volume of roller-compacted ribbons (Table 2). Direct volume measurement is the easiest to implement but can be tedious when used routinely; it also lacks accuracy when applied to textured ribbons. Volume displacement is a better approach for measuring complex shapes and is not subject to operator variability and bias. Yet it requires cutting the ribbon into pieces small enough to fit inside a sample chamber. Another option is laser scanning, in which a laser micrometer pair is coupled with motion control to traverse the sample and create a two-dimensional (2D) pattern of it. Laser scanning can also be used to profile ribbon thickness and thus calculate its volume. The most direct way to determine apparent density is to cut the ribbon into rectangular pieces, measure their dimensions, and weigh them to calculate envelope vol - ume. Despite its relatively poor precision, this tech nique is often the primary method for calibrating the roller compactor. But using volume displacement or laser scanning provides substantially more accurate and precise measurements of apparent density. While this article focuses on applying terahertz tech - nology to roller-compacted ribbons, other tech niques can also measure density profiles (Table 3). Each has its advantages, but the terahertz method stands out as a fast, non-destructive, non-contact technique suitable for spatial mapping and in-line process applications. In addition, most pharmaceutical materials are highly transparent to terahertz radiation, which can penetrate approximately 10 milli - meters into the material. There fore, terahertz samples the entire ribbon thickness, not just the surface. It is also highly precise and sensitive to changes in apparent density. Theory of terahertz density measurement The unique characteristics of pulsed terahertz spec - troscopy make it well suited for measuring the densities of solid compacts. The terahertz source (emitter) generates a very narrow, phase-coherent pulse of light that reaches a phase-sensitive detector whose fast digit - ization rate makes it possible to measure in the pico - second range. When a terahertz pulse passes through a homogeneous solid, its speed decreases relative to a terahertz pulse that traverses the same distance through air. The ratio of the speed of light in air to the speed of light in a denser material is, in fact, the definition of the refractive index (RI) of that material. The time difference Table 1 Material properties of roller-compacted ribbons Material property Definition Apparent density Weight 4 envelope volume or bulk density (where envelope volume is obtained by direct measurement of the dimensions of the compact) Solid fraction Apparent density 4 true density (where true density is the material density in the absence of voids) Percentage porosity (1 2 solid fraction) • 100% Table 2 Techniques for measuring envelope volume Technique Device Advantages Disadvantages Direct measurement Micrometer caliper Low cost Destructive, manual, subject to operator variability, poor spatial resolution Volume displacement Pycnometer Accurate for irregular shapes Destructive (sample cut to fit in chamber), (e.g., textured ribbons), not subject poor spatial resolution to operator variability Laser scanning Laser micrometer Fast, non-destructive, suitable Sensor array or traversing sensor for in-line applications required for ribbon profiling