Patient nonadherence to medication regimens has major effects on patient health and costs the healthcare system billions of dollars each year.  Adherence rates, as well as pharmacology, may be improved by formulating medicines to be dosed less frequently (e.g., once weekly rather than once daily).  Lyndra Therapeutics has recently demonstrated multi-day oral drug delivery in humans using a gastric resident dosage form.<br/>The gastric resident formulation is taken orally inside a standard sized capsule.  As the capsule dissolves in the stomach it releases a star-shaped formulation composed of biocompatible polymers.  The geometry and physical properties of the star-shaped formulation allow it to remain resident in the stomach by preventing passage through the pylorus.  Drug is released steadily over the course of several days in the stomach.  After drug release, structural components of the formulation, called disintegrating matrices (DM), begin to soften and can break, allowing the dosage form to deform and to pass through the pylorus for safe passage out of the body.  The controlled softening of DM materials is essential to tuning the timing of gastric exit of the formulation and the frequency of dosing. Here we discuss the development of DM materials that are designed for controlled weakening in the stomach environment to drive passage of the formulation after about one week of gastric residence.<br/>The timing DM is a polymer blend that connects distinct components of the dosage form.  In aqueous media, hydrolysis of polymer drives softening of the matrix. The matrix was formulated to maintain structural integrity for one week, and to subsequently weaken to an extent that allows deformation of the dosage form.  A second polymer was incorporated into the matrix to minimize matrix softening upon initial hydration.  By varying the composition of the polymer matrix, a formulation was identified that demonstrated loss of structural integrity over the desired time course. DM formulations were manufactured by hot-melt extrusion and their stiffness was evaluated by 3-point bending after incubation in simulated gastric media. The DM material was incorporated into dosage forms through thermal bonding, and the thermal bond strength was evaluated by tensile testing and dynamic mechanical testing.

Development of time-responsive disintegrating matrices for 7-day oral drug delivery

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.