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