Systems and methods for superdisintegrant-based composite particles for dispersion and dissolution of agents

摘要

The present disclosure provides improved systems and methods utilizing colloidal/ultrafine superdisintegrant-based composite particles for dispersion and/or dissolution of active pharmaceutical agents. In general, the present disclosure utilizes a surfactant-free or near surfactant-free formulation by incorporating a wet milled SDI as a dispersant in the formulation. As such, the present disclosure provides for the preparation of surfactant-free or substantially surfactant-free formulations (e.g., nano-composite micro-particle formulations) by incorporating a wet-milled superdisintegrant (SDI) as the dispersant in the formulations. The advantageous SDI particles (e.g., colloidal/ultrafine SDI particles) of the present disclosure can be used to break-up the aggregates (e.g., nanoparticle aggregates) of the active agents (e.g. poorly water-soluble drugs) in the formulations (e.g., micro-particle formulations) and enhance the recovery of the nanoparticles of active agents during aqueous re-dispersion and their dissolution rate in vitro and in vivo.

主权项

1. A method for fabricating a formulation comprising:
providing active agent particles in an aqueous suspension; introducing the aqueous suspension of active agent particles to a wet media mill having a milling chamber; pumping the aqueous suspension of active agent particles through the wet media mill; operating the wet media mill at a pre-determined rpm setting; periodically and gradually introducing superdisintegrant (SDI) particles to the aqueous suspension of active agent particles in the operating wet media mill to form an aqueous suspension of SDI particles and active agent particles in the operating wet media mill; co-wet-milling the aqueous suspension of SDI particles and the active agent particles in the operating wet media mill to form a co-wet-milled suspension of co-wet-milled SDI particles and active agent particles, the co-wet-milled suspension including colloidal and ultrafine SDI particles and colloidal particles and nanoparticles of active agents; drying the co-wet-milled suspension of SDI particles and active agent particles to form a composite of SDI particles and active agent particles; wherein the co-wet-milled SDI particles have a particle size of less than about 5 microns; wherein the SDI particles and active agent particles are co-wet-milled in the wet media mill with milling media.