An evaluation of six techniques for measuring porosity of ribbons produced by roller compaction
Abstract
Ribbon porosity is a critical parameter to monitor in the roller compaction process. In this study, six techniques for measuring the porosity of solid compacts, i.e., manually by caliper (Caliper), X-ray microtomography (µCT), off-line near-infrared spectroscopy (NIR), laser triangulation (Laser), mercury intrusion porosimetry (MIP), and GeoPyc, were compared using a set of rectangular ribblets of microcrystalline cellulose (MCC). These ribblets, which were compressed at 8–130 MPa on a compaction simulator, exhibited porosities over the range of 0.09 – 0.52. Subsequently, porosities of MCC ribbons made on a roller compactor at specific roll forces of 1.8 kN/cm and 8.8 kN/cm were measured. The Caliper method is convenient for samples with a simple shape but not suitable for real ribbons. The accuracy of GeoPyc measurement relies on accurate conversion factor (unit in cm3/mm), sample shape and size, and sufficient sample volume percentage in the medium. The µCT data is more accurate at lower porosities (< 0.2), while the MIP data is more accurate at higher porosities (> 0.4). The Laser method has good accuracy and is more reproducible compared to other methods in the ribblets measurement. The NIR method is fast, which makes it suitable for in-line monitoring of changes in ribbon quality, but porosity quantification is sensitive to sample presentation, such as surface curvature and roughness. These insights could assist in the choice of the most appropriate method for monitoring ribbon porosity to guide the development and optimization of a roller compaction process for a given formulation.
Introduction
Ribbon porosity, ε, represents the fraction of voids in a specimen. It is a critical quality attribute (CQA) for ribbons produced in roller compaction (RC) because it directly affects the subsequent granule and tablet properties (Yu et al., 2014). Since ε is calculated from the knowledge of a solid sample density (ρbulk) and true density (ρtrue) using Eq. (1), ribbon density monitoring and control is an important consideration during scale-up (Boersen et al., 2016), processes transfer (Souihi et al., 2015), and modeling and simulations of a RC process (Nesarikar et al., 2012, Reimer and Kleinebudde, 2019).
Where ρbulk/ρtrue is the solid fraction of the solid compacts, in which true density of the material, ρtrue, may be determined using different methods (Richards and Lindley, 2006), including calculation from single crystal structures (Elsergany et al., 2023), helium pycnometry (Chang et al., 2019), buoyancy method (Goldenberg et al., 2023), the Sun method (Sun, 2004), and in-die stress transmission method (Elsergany et al., 2023). The density of a solid sample, ρbulk, is calculated from sample mass, m, and envelop volume, V, (Eq. (2)).ρbulk=mV
Since m can be accurately measured using a suitable analytical balance, ρbulk can be determined if V is known. Currently, several techniques are available for determining the V of samples, such as GeoPyc (Zinchuk et al., 2004), laser triangulation (Laser) (Lillotte et al., 2021), or caliper (Caliper) for samples with a simple geometry, e.g., rectangular (Keizer and Kleinebudde, 2020) or cylindrical tablets (Osei-Yeboah and Sun, 2015). Porosity can also be directly measured by mercury intrusion porosimetry (MIP, Khorasani et al., 2015a, Lu et al., 2000) or predicted from a measurable physical property based on a known calibration curve with density. The latter includes X-ray microtomography (µCT) (Mahmah et al., 2019, Miguélez-Morán et al., 2009), near-infrared spectroscopy (NIR) (Crowley et al., 2017, Khorasani et al., 2015b, Lim et al., 2011), and terahertz spectroscopy (Bawuah et al., 2020, Zhang et al., 2016).
Each of these methods has its advantages and limitations in terms of accuracy, precision, sensitivity, measurement speed, ease of operation, sample preparation and amount, and capability for mapping. Thus, a suitable measurement method needs to be judicially selected according to application scenarios, such as at −, on −, or in − line process monitoring to overcome limitations of end product testing and to guide continuous manufacturing, or mapping to understand the density/porosity distribution inside a ribbon. In this study, six commonly used techniques for measuring porosity of ribbons in the context of dry granulation were compared, including Caliper, GeoPyc, Laser, µCT, MIP, and off-line NIR methods, and both simulated ribbons (ribblets, a combination of the words ribbon and tablet) (Keizer, 2021) from a compaction simulator and ribbons prepared using a roller compactor were used. To our best knowledge, there are similar studies, however with fewer number of techniques, such as comparing a Laser mehtod to an oil intrusion method (Allesø et al., 2016), a Laser technique to GeoPyc method and a Caliper method (Iyer et al., 2014), terahertz imaging method to a section method where small pieces cut from a ribbon by a bandsaw was manually measured by a caliper (Zhang et al., 2016), and µCT method to Laser and GeoPyc methods (Lillotte et al., 2021). Along with these studies, this work is aimed at better understanding the pros and cons of these methods, and facilitates the selection of the most appropriate technique for ribbon porosity measurement to guide RC process development.
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Materials
Microcrystalline cellulose (MCC, Avicel 105, International Flavors & Fragrances, Philadelphia, PA) was used as received.
Sample preparation
Ribblets were prepared by a uniaxial compaction simulator (Styl’One Evolution, MEDELPHARM, Beynost, France), using rectangular shaped flat faced tooling (16 × 9 mm). Ribblets were compressed at seven compaction pressures in the range of 8–130 MPa under a force control mode, resulting porosities covering a range of 0.09–0.52.
Yiwang Guo, Lizbeth Martinez, Arnesh Palanisamy, Bindhu Gururajan, Changquan Calvin Sun, An evaluation of six techniques for measuring porosity of ribbons produced by roller compaction, International Journal of Pharmaceutics, Volume 667, Part A, 2024, 124855, ISSN 0378-5173, https://doi.org/10.1016/j.ijpharm.2024.124855.
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