Insights into the Control of Drug Release from Complex Immediate Release Formulations

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 R2>0.995). 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.

Tablet formulation development focusing on the functional behaviour of water uptake and swelling

“…Dong et al reported an inhibition of water penetration and hence lower swelling of tablets containing a solid dispersion based on HPMC due to the formation of a gel layer. High amounts of MCC promote tablet hydration, as the material swells more rapidly and no gelling occurs ( Dong et al, 2021 ). This might be in good agreement with the comparable behaviour of the investigated tablet formulations containing Kollidon VA64 and MCC displayed in Fig.…”

Drug-Release Mechanisms Elucidated by Imaging Techniques: Visualizing the Invisible!

“…Dong and co-workers investigated water transport into immediate-release tablets of varying formulations and microstructures [4]. With these types of tablets, water transport is of utmost importance to control drug release and tablet disintegration.…”