Characterisation of pore structures of pharmaceutical tablets: A review

Abstract

Traditionally, the development of a new solid dosage form is formulation-driven and less focus is put on the design of a specific microstructure for the drug delivery system. However, the compaction process particularly impacts the microstructure, or more precisely, the pore architecture in a pharmaceutical tablet. Besides the formulation, the pore structure is a major contributor to the overall performance of oral solid dosage forms as it directly affects the liquid uptake rate, which is the very first step of the dissolution process. In future, additive manufacturing is a potential game changer to design the inner structures and realise a tailor-made pore structure. In pharmaceutical development the pore structure is most commonly only described by the total porosity of the tablet matrix. Yet it is of great importance to consider other parameters to fully resolve the interplay between microstructure and dosage form performance. Specifically, tortuosity, connectivity, as well as pore shape, size and orientation all impact the flow paths and play an important role in describing the fluid flow in a pharmaceutical tablet. This review presents the key properties of the pore structures in solid dosage forms and it discusses how to measure these properties. In particular, the principles, advantages and limitations of helium pycnometry, mercury porosimetry, terahertz time-domain spectroscopy, nuclear magnetic resonance and X-ray computed microtomography are discussed.

In-situ Monitoring of Powder Density Using Terahertz Pulsed Imaging

“…was thus calculated from the terahertz reflection measurements and we reveal in this study that the surface refractive index averaged around the entire container, , is linearly related to ̅ for the six different investigated powders. These observations are in line with our previous studies about the relative density of powder compacts, where the refractive index is also linearly related to the porosity [1]. A linear model was thus fitted for each material to relate to ̅ in order to predict the powder density from each individual terahertz reflection measurements (Fig.…”

“…A very promising method to measure the relative density of pharmaceutical materials is terahertz technology as it has been demonstrated for powder compacts (pharmaceutical tablets) of various formulations [1]. The relative density of tablets is typically calculated from the effective refractive index of the compact measured by terahertz time-domain spectroscopy [1].…”

“…A very promising method to measure the relative density of pharmaceutical materials is terahertz technology as it has been demonstrated for powder compacts (pharmaceutical tablets) of various formulations [1]. The relative density of tablets is typically calculated from the effective refractive index of the compact measured by terahertz time-domain spectroscopy [1]. Since terahertz radiation can relatively easily penetrate through typical pharmaceutical materials, most previous studies focused on measuring samples in transmission which was demonstrated for tablet thicknesses of up to 5.3 mm [2].…”

Prediction of diffusive transport through polymer films from characteristics of the pore geometry

“…Advances in computational power over the last decades have made possible numerical simulation of mass transport in the complicated geometric structures obtained from the microscopy images . Connecting the microstructure in the images to transport properties is important in fields as diverse as composite materials design, electrochemical engineering, the oil and gas industry, and biomedical and pharmaceutical science . Our work concerns porous polymer films which are used as coatings to control the rate of drug release from pharmaceutical pellets.…”

WITHDRAWN: 3D characterisation of dry powder inhaler formulations: Developing X-ray micro computed tomography approaches

“…The need to fully characterise the microstrucure of DPI formulations has recently become more important due to the introduction of "microstructural equivalence" from the Food and Drug Administration (FDA) [35,37,50]. To this end, X-ray computed tomography (XCT) [19,39] has increasingly gained interest as a non-destructive technique to study the microstructure of pharmaceutical formulations.…”