Abstract
The kinetics of water transport into tablets, and how it can be controlled by the formulation as well as the tablet microstructure, are of central importance in order to design and control the dissolution and drug release process, especially for immediate release tablets. This research employed terahertz pulsed imaging to measure the process of water penetrating through tablets using a flow cell. Tablets were prepared over a range of porosity between 10% to 20%. The formulations consist of two drugs (MK-8408: ruzasvir as a spray dried intermediate, and MK-3682: uprifosbuvir as a crystalline drug substance) and NaCl (0% to 20%) at varying levels of concentrations as well as other excipients. A power-law model is found to fit the liquid penetration exceptionally well (average ). For each formulation, the rate of water penetration, extent of swelling and the USP dissolution rate were compared. A factorial analysis then revealed that the tablet porosity was the dominating factor for both liquid penetration and dissolution. NaCl more significantly influenced liquid penetration due to osmotic driving force as well as gelling suppression, but there appears to be little difference when NaCl loading in the formulation increases from 5% to 10%. The level of spray dried intermediate was observed to further limit the release of API in dissolution.
Highlights
Immediate release tablets are designed to rapidly disintegrate and release drug substance after administration
The liquid penetration profiles of all batches were plotted for each study together with the dissolution profiles of the corresponding formulations to allow for comparison (Figure 2)
The extent of dissolution, as determined by USP dissolution testing, is expressed in terms of a faction of drug dissolved over the range of 0 to 1 where 1 corresponds to complete drug release and dissolution
Summary
Immediate release tablets are designed to rapidly disintegrate and release drug substance after administration. Disintegration is a complex process that involves a combination of dissolution medium wicking into the porous tablet, particle swelling, strain recovery and rapid dissolution [1]. These processes are in turn affected by the interplay of formulation and processing conditions which determine the physical properties and microstructure of the tablets [2]. The pharmacopeial disintegration test results in a single value of disintegration time for a batch of tablets under test. It is of relatively limited use as a stand-alone tool to gain quantitative or mechanistic insight into the process
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