Pharmacy Courses

Hydrophilic Matrix forming Tablets


Hydrophilic matrices have been used since the 1960s and have been the most popular oral CR (control release) technology to this day. They use the same established and cost-effective process technology as are used to produce conventional tablets, such as blending, granulation (dry or wet), compression and film-coating, making them operationally largely indistinguishable.

They can also deliver high unit doses of API and be used for APIs with different properties, which makes them so attractive to industry. However, unlike IR tablets, CR matrices require at least one higher viscosity polymer that hydrates quickly and forms a pseudo-gel layer on the tablet surface. Rapid formation of this layer is critical to prevent disintegration of the core and to control water ingress and drug release rates.

Since the release-controlling pseudo gel layer only forms after tablet exposure to fluid, there are intrinsic robustness risks associated with this transition period. Specifically, any factors interfering with pseudo-gel layer formation can have undesired effects in vivo or in vitro, potentially altering the release profile significantly. The latter can be affected by factors such as tablet geometry, polymer type and concentration, API and excipient solubility and the fluid they are exposed to, most of which are discussed in Section. Matrix tablets are hence not as easy to design as they are to manufacture.

Key Formulation Constituents of Matrix forming Tablet

  • Release-controlling Polymer (The E- and K-series have been the preferred chemistries for matrix tablets for many years, especially the K-chemistry, which is associated with fast hydration and pseudo-gel formation, due to the highest hydroxypropoxyl to methoxyl ratio.)
  • Other Formulation Constituents (Since hydrophilic matrices use the same process technology as conventional tablets, they require similar functional excipients. These are hence not discussed in any detail here. However, their solubility characteristics can affect drug release. Specifically, soluble components will wet, dissolve and diffuse out of the matrix, while insoluble material generally remains in place until the surrounding polymer/ excipient/drug-complex has eroded or dissolved away.)

Drug Release Mechanisms

API release from matrix tablets can occur via diffusion, through the pseudo-gel, or via tablet surface erosion.

  • Diffusion-based Matrix Tablets: Diffusion has historically been the primary release mechanism of hydrophilic matrices, since they were developed predominantly for soluble APIs. A key limitation of diffusion-based matrices is that adequate release rates are only achieved if there is sufficient API dissolution within the tablet. The dissolution potential in the tablet is orders of magnitude lower than that in the surrounding environment (e.g. 900 ml dissolution media), due to the much higher solid-to-liquid-ratio within the tablet.
  • Erosion-based Matrix Tablets: Classic hydrophilic matrices only offer limited opportunities for low-solubility APIs, due to the limitations of diffusion-based drug release. However, a shift of release mechanism from diffusion to erosion would, in principle, enable the use of matrix tablets for low-solubility APIs. A key difference between diffusion- and erosion-based matrices is that the latter require lower viscosity polymers, e.g. HPMC K100lV or K4M, since API release is governed by the rate of surface erosion (which exposes non-dissolved API to the surrounding fluid).

Previous Post Next Post