Advances in Mechanistic Understanding of Release Rate Control Mechanisms of extended-release Hydrophilic Matrix Tablets

Abstract

Approaches to characterizing and developing understanding around the mechanisms that control the release of drugs from hydrophilic matrix tablets are reviewed. While historical context is provided and direct physical characterization methods are described, recent advances including the role of percolation thresholds, the application on magnetic resonance and other spectroscopic imaging techniques are considered. The influence of polymer and dosage form characteristics are reviewed. The utility of mathematical modeling is described. Finally, how all the information derived from applying the developed mechanistic understanding from all of these tools can be brought together to develop a robust and reliable hydrophilic matrix extended-release tablet formulation is proposed.

Formulation of Sustained Release Hydrophilic Matrix Tablets of Tolcapone with the Application of Sedem Diagram: Influence of Tolcapone’s Particle Size on Sustained Release

“…The drug is distributed in a matrix that is usually polymeric. This matrix hinders the access of the solution medium to the surface of the particles and make the drug diffusion towards the outside matrix difficult [ 3 ].…”

“…As the polymeric excipient constituting the matrix is hydrated, gelation proceeds at some speed towards the solid core, where the polymer is in a non-hydrated state. In the erosion mechanism, the external gelled layer, when eroded, also contributes to the process of sustained release of the active ingredient [ 3 ].…”

Imaging of the Effect of Alcohol-Containing Media on the Performance of Hypromellose Hydrophilic Matrix Tablets: Comparison of Direct Compression and Regular Grades of Polymer

“…Modifying the kinetics of drug release from orally administered solid dosage forms can be attained by formulating the drug to include a hydrophilic polymeric matrix, using swellable polymers such as hypromellose (hydroxypropyl methylcellulose, HPMC), poly(ethylene oxide) and hydroxypropylcellulose. When the hydrophilic polymer is exposed to water or biological fluids, it becomes hydrated, swells and forms a gel layer (the zone between the erosion front and the swelling front) around an initially dry core, which can delay the diffusion of an incorporated drug from the polymeric matrix [ 6 , 7 , 8 , 9 ]. This gel layer hydration process is dynamic, with the gel layer growing over time due to further inward migration of fluid, as well as swelling of the gel layer and erosion of the gel layer due to shear forces in the environment in which the dosage form sits (agitation in an in vitro test, peristaltic forces in vitro).…”

Development of a novel method utilising dissolution imaging for the measurement of swelling behaviour in hydrophilic matrices

“…Due to the extensive use of hypromellose within the pharmaceutical industry, the polymer is well characterised, with studies focusing on the influence of initial dissolution (Campos-Aldrete and Villafuerte-Robles, 1997), particle size (Heng et al, 2001), morphology on drug release (Bonferoni et al, 1996). Better mechanistic understanding of factors associated with performance of hypromellose in extended release hydrophilic matrix tablets will contribute to a robust quality-by-design approach to these products (Timmins et al, 2016).…”