Microfluidic Particle Engineering of Hydrophobic Drug with Eudragit E100─Bridging the Amorphous and Crystalline Gap

Abstract

Co-processing active pharmaceutical ingredients (APIs) with excipients is a promising particle engineering technique to improve the API physical properties, which can lead to more robust downstream drug product manufacturing and improved drug product attributes. Excipients provide control over critical API attributes like particle size and solid-state outcomes. Eudragit E100 is a widely used polymeric excipient to modulate drug release. Being cationic, it is primarily employed as a precipitation inhibitor to stabilize amorphous solid dispersions. In this work, we demonstrate how co-processing of E100 with naproxen (NPX) (a model hydrophobic API) into monodisperse emulsions via droplet microfluidics followed by solidification via solvent evaporation allows the facile fabrication of compact, monodisperse, and spherical particles with an expanded range of solidstate outcomes spanning from amorphous to crystalline forms. Low E100 concentrations (≤26% w/w) yield crystalline microparticles with a stable NPX polymorph distributed uniformly across the matrix at a high drug loading (∼89% w/w). Structurally, E100 incorporation reduces the size of primary particles comprising the co-processed microparticles in comparison to neat API microparticles made using the same technique and the as-received API powder. This reduction in primary particle size translates into an increased internal porosity of the co-processed microparticles, with specific surface area and pore volume ∼9 times higher than the neat API microparticles. These E100-enabled structural modifications result in faster drug release in acidic media compared to neat API microparticles. Additionally, E100-NPX microparticles have a significantly improved flowability compared to neat API microparticles and as-received API powder. Overall, this study demonstrates a facile microfluidics-based co-processing method that broadly expands the range of solid-state outcomes obtainable with E100 as an excipient, with multiscale control over the key attributes and performance of hydrophobic API-laden microparticles.

On-Demand Sequential Release of Dual Drug from pH-Responsive Electrospun Janus Nanofiber Membranes toward Wound Healing and Infection Control

“…One possible explanation for the reduced initial burst release of OCT, as well as enhanced release and solubility of CUR, is the chemical bonding or interfacial interaction between the two sides of the Janus nanofiber consisting of a pH-responsive compartment and a nondegradable compartment. In an acidic medium, the protonation of tertiary amine groups, which promotes the dissolution of the EE compartment, could form colloidal dispersion with poorly water-soluble curcumin in the interface region of the P-PMMA compartment, leading to enhanced curcumin release from Janus nanofibers. , This release mechanism corresponded with CUR release profiles, suggesting that an anisotropic Janus structure with two faces consisting of opposite physicochemical properties is an efficient strategy to overcome major challenges associated with a poorly soluble drug’s therapeutic use and provides a simple clinical translation.…”

Orthogonal Gelations to Synthesize Core–Shell Hydrogels Loaded with Nanoemulsion‐Templated Drug Nanoparticles for Versatile Oral Drug Delivery

“…Crystallizing API inside an excipient matrix (so‐called “co‐processing”), can enable excipient‐stabilized nanocrystals. [ 7,87 ] In sum, this approach can be a scalable method to manufacture drug nanocrystals.…”