(189v) Development of pH -Responsive Disintegrating Matrices for Safe Intestinal Transit of Gastric Resident Dosage Forms

Multi-day oral drug delivery has recently been demonstrated in humans using a unique gastric resident dosage form pioneered by Lyndra Therapeutics. After oral administration in a standard sized capsule, the polymer-based dosage form unfolds in the stomach into a stellate geometry that is large enough to prevent passage through the pylorus and is able to withstand gastric emptying waves. Once the stellate has fully eluted its drug contents, it will exit the low-pH gastric environment and encounter the high-pH intestinal environment. To facilitate intestinal transit of dosage form components, enteric disintegrating matrix (DM) materials were developed that provide structure to the stellate at gastic pH but lose their physical integrity upon exposure to intestinal pH.

The enteric disintegrating matrix (DM) is an HPMCAS-based polymer blend that connects the drug-containing arms to the body of the dosage form. When exposed to high pH during intestinal transit, the enteric DM softens and can break, reducing the overall size of the dosage form. This promotes safe exit through the intestinal tract.

By varying the composition of the polymeric matrix, a formulation was developed that demonstrated structural integrity for 7 days in a simulated gastric environment and quickly lost structural integrity upon exposure to a simulated intestinal environment. Robust DMs were successfully manufactured by via hot-melt extrusion and evaluated by 3-Pt Bending, water uptake in gastric media, mass loss in intestinal media, and morphology via SEM. The materials were incorporated into dosage forms by thermal bonding, and the thermal bond strength was evaluated via tensile testing and dynamic mechanical testing.