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

Abstract

Hydrophobic active pharmaceutical ingredients are ubiquitous in the drug development pipeline, but their poor bioavailability often prevents their translation into drug products. Industrial processes to formulate hydrophobic APIs are expensive, difficult to optimize, and not flexible enough to incorporate customizable drug release profiles into drug products. Here, a novel, dual‐responsive gelation process that exploits orthogonal thermo‐responsive and ion‐responsive gelations is introduced. This one‐step “dual gelation” synthesizes core‐shell (methylcellulose‐alginate) hydrogel particles and encapsulates drug‐laden nanoemulsions in the hydrogel matrices. In situ crystallization templates drug nanocrystals inside the polymeric core, while a kinetically stable amorphous solid dispersion is templated in the shell. Drug release is explored as a function of particle geometry, and programmable release is demonstrated for various therapeutic applications including delayed pulsatile release and sequential release of a model fixed‐dose combination drug product of ibuprofen and fenofibrate. Independent control over drug loading between the shell and the core is demonstrated. This formulation approach is shown to be a flexible process to develop drug products with biocompatible materials, facile synthesis, and precise drug release performance. This work suggests and applies a novel method to leverage orthogonal gel chemistries to generate functional core‐shell hydrogel particles.This article is protected by copyright. All rights reserved

Surfactant–Polymer Complexation and Competition on Drug Nanocrystal Surfaces Control Crystallinity

“…Using this workflow, we simulate the effect of surfactant weight fraction at experimentally realistic compositions on the crystal structure and dynamics. We corroborate our simulation results using the bottom-up nanocrystallization method developed in our group − to relate the excipient composition and interfacial structure to the experimentally observed extent of crystallinity. These are the first simulations that directly characterize structural changes in a drug crystal as a result of excipient surface composition and relate experimental extent of crystallinity to molecular-level structure.…”

“…Such bottom-up methods tend to blur the boundaries between drug substance and drug product manufacturing by including excipients in the crystallization process . For example, one such bottom-up process, flash nanoprecipitation, produces polymer-coated drug nanoparticles through antisolvent precipitation in a turbulent mixing device. , Another approach developed in our research group crystallizes drug nanoparticles by encapsulating and then evaporating drug-loaded nanodroplets inside hydrogel matrices, enabling high drug-loaded formulations of hydrophobic APIs with controllable drug release. − In parallel, formulating hydrophobic drugs into ASDs has also improved the dissolution and bioavailability for many drugs . ASDs exploit the ability of a polymer matrix to stabilize amorphous aggregates of drug molecules and inhibit crystallization, which promotes rapid drug release during delivery .…”

Wondrous Yellow Molecule: Are Hydrogels a Successful Strategy to Overcome the Limitations of Curcumin?

“…They encapsulate the drug in their matrix, which allows the administration of the drug orally, topically, or parenterally, with specific, targeted properties with controlled or delayed release. This formulation increases the bioavailability of hydrophobic drugs and enables combining several compounds in one hydrogel matrix [25][26][27][28]. Considering the above-discussed properties of hydrogels, these matrices can be used as a promising delivery system for low soluble hydrophobic therapeutic agents such as curcumin.…”