pH-sensitive lyotropic liquid crystal beads designed for oral zero-order extended drug release
Year: 2025
Type: article
Abstract: • Novel preparation method of lyotropic liquid crystal beads from micellar solutions. • A method of adjusting the drug release rates from liquid crystals. • The micellar structural mobility is maintained throughout the drug release process. • Abrupt structural changes induce gradual shifts in the structural mobility. • Mechanisms of drug release from lyotropic liquid crystals are discussed. The present study introduces a novel formulation approach for utilizing Lyotropic Liquid Crystals (LLCs) as sustained oral delivery systems. For this purpose, we have developed a novel bottom-up fabrication process that enables the LLC beads to be formulated with precise control over their diameter by pre-determining their surface area. By directly controlling the effective diffusional interfacial surface of the LLCs, their release rate from the LLC beads can be determined. The LLC beads were formulated as pH-responsive systems, attenuating the Higuchian primary diffusional burst in a gastric environment, and increasing the release of the solubilized load at an elevated pH environment (pH 6.4). To demonstrate the applicability of this approach, the LLC beads were loaded with a lipophilic low water solubility (< 5 µg/mL) model drug, Celecoxib (CLXB). Although the CLXB water solubility is not pH dependent, CLXB’s Higuchian release constant increased from 9.31 at pH 1.5 to 15.03 at pH 6.4. The pH dependency of CLXB release was achieved by the co-solubilization of additional compounds in the LLC structure, creating a pH-dependent environment that influences both the LLC structure and the release of the co-solubilized compounds. The enhanced release of CLXB in an elevated pH environment enables gaining a zero-order (R 2 > 0.99) sustained release profile extending beyond 10 h in a release medium simulating the gastrointestinal (GI) tract environment. Additionally, the study investigated the association between the release of co-solubilized compounds and the micellar structure using techniques such as small-angle X-ray diffraction, nuclear magnetic resonance, and electron paramagnetic resonance. The results revealed a co-dependent relationship between the release of lipophilic compounds and changes in the curvature of LLCs at different pH levels, suggesting that a compensatory mechanism operates between these two processes. These insights, combined with the innovative bottom-up fabrication method for LLC beads, provide valuable tools for controlling the release of lipophilic compounds from LLCs and for enhancing their effectiveness as controlled oral delivery systems.
Institutions: Hebrew University of Jerusalem, University of Urbino
Language: English
Subfield: Pharmaceutical Science
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,650
OpenAlex ID: W4408360718