Abstract
Cost effectiveness, ease of use and patient compliance make pharmaceutical tablets the most popular and widespread form to administer a drug to a patient. Tablets typically consist of an active pharmaceutical ingredient and a selection from various excipients. A novel highly porous excipient, functionalised calcium carbonate (FCC), was designed to facilitate rapid liquid uptake leading to disintegration times of FCC based tablets in the matter of seconds. Five sets of FCC tablets with a target porosity of 45–65% in 5% steps were prepared and characterised using terahertz pulsed imaging (TPI). The high acquisition rate (15Hz) of TPI enabled the analysis of the rapid liquid imbibition of water into these powder compacts. The penetration depth determined from the TPI measurements as a function of time was analysed by the power law and modelled for both the inertial (initial phase) and Lucas-Washburn (LW, longer time Laplace-Poiseuillian) regimes. The analysis of the hydraulic radius estimated by fitting the liquid imbibition data to the LW equation demonstrates the impact of the porosity as well as the tortuosity of the pore channels on the liquid uptake performance. The tortuosity was related to the porosity by a geometrical model, which shows that the powder compact is constructed by aggregated particles with low permeability and its principal axis perpendicular to the compaction direction. The consideration of the tortuosity yielded a very high correlation (R2=0.96) between the porosity and the hydraulic pore radius. The terahertz data also resolved fluctuations (0.9–1.3Hz) of the liquid movement which become more pronounced and higher in frequency with increasing porosity, which is attributed to the constrictivity of pore channels. This study highlights the strong impact of a tablet's microstructure on its liquid penetration kinetics and thus on its disintegration behaviour.
Highlights
Pharmaceutical tablets are well-known as being amongst the most convenient ways of delivering active pharmaceutical ingredient (API) to the patient
Since the intra-particle pore structure of the functionalised calcium carbonate (FCC) particles is similar between the different batches (Markl et al, 2017b), the variations in liquid uptake kinetics of the different batches are primarily affected by the inter-particle pore architecture which was formed during powder compaction
The observed correlation between porosity and liquid imbibition kinetics suggests that each powder compact is an homologous series of structures, in that the features of connectivity and pore size distribution remain related to porosity, i.e. the basic descriptors of the pore structure remain constant or vary continuously in line with the varied tablet compression
Summary
Pharmaceutical tablets are well-known as being amongst the most convenient ways of delivering active pharmaceutical ingredient (API) to the patient. The design of targeted drug release and vector delivery requires specialist development of functional excipients, for example, to encapsulate an API to provide protective access into the small and large intestine or to provide rapid oral disintegration. The performance of an ODT is limited by the rate saliva penetrates into the tablet leading to swelling of the (superdisintegrant) particles and eventually causing the break-up of the compact into small agglomerates or the original constituents’ particles. The understanding of this process is severely limited, partly due to the complex nature of the process itself and partly due to the lack of suitable measurement techniques. Alternative methods to measure rapid disintegration are highly desirable to evaluate ODTs and to control the quality of such drug products
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