Hypromellose-Dyphylline Interaction in HPMC Matrix Tablets

Hypromellose-Dyphylline Interaction in HPMC Matrix Tablets

Hypromellose (HPMC) matrices are a popular approach in the formulation of extended release drug delivery systems.hongyuan hpmc High viscosity grades of HPMC are widely used as rate-controlling polymers in these formulations due to their wide availability, global regulatory compliance, and physicochemical properties (1).hongyuan hpmc Upon exposure to aqueous or hydroalcoholic solutions, matrices hydrate and form gel layers which control water transport through the matrix and drug release (2). The gel strength of a hydrated matrix is influenced by several factors, including the polymer supply source and the drug solubility (3). It is therefore important to understand the influence of hydration and gel strength on the textural behavior and drug release from HPMC matrix tablets.

In this study, we investigated the interaction of hydroxypropyl methylcellulose acetate succinate (HPMC-AS) with the pharmacologically active substance dyphylline by performing hot melt extrusion (HME) experiments and analyzing the resulting products by ion chromatography and HPLC.hongyuan hpmc During the HME process, HPMC-AS undergoes significant hydrolysis at elevated temperatures and produces free acetic acid and succinate esters (4).hongyuan hpmc These esters can react with hydroxyl groups on the dyphylline structure, potentially causing an incompatibility issue during formulation development (5).

Our experimental results demonstrated that the hydrated HPMC matrix tablets exhibited a gel-like texture irrespective of the ethanol concentration in the aqueous and hydroalcoholic solutions tested.hongyuan hpmc The rheological properties of the matrices were also unchanged when exposed to the aqueous and alcoholic solutions. However, the permeability of the matrices significantly increased when exposed to the aqueous solution with ethanol.

The textural profiles of the matrices exhibited that a homogenous HPMC batch shows a hydration behavior ascribable to Fick’s law, while a more heterogeneous HPMC batch exhibits an abrupt step change in the water concentration in the gel layer.hongyuan hpmc The hydration of the matrix was also influenced by a pH value, which may be a consequence of the different degree of chemical modification in the HPMC batches.

In the aqueous diluent, the hydrates formed by all the HPMC grades showed similar work of penetration values at 1 and 2 h after hydration, while the gradient and gradient of hydration was affected more by the initial exposure to the alcoholic solution.hongyuan hpmc However, after 4 and 6 h of hydration, the differences in the rheological and textural properties become smaller. This suggests that, over a longer period of time, the morphological properties and the permeability of hydrated HPMC compacts should not be influenced by the initial exposure to the alcoholic solutions. The aqueous diluent was found to be the best solvent for the hydration of the matrices, and it should be employed in future HPMC matrix tablet formulations to avoid dose-dumping. Further investigations should be performed to further evaluate the impact of alcoholic solutions on the textural and rheological properties of HPMC. The synthesis of novel low-molecular weight cellulose compounds, based on the formation of adducts between cellulose ethers and hydroalcoholic solutions is an exciting avenue for further investigation (6).

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