Intestinal-retaining fluid gel formulations for oral medication delivery in post-stroke dysphagia management

Abstract

Patients with post-stroke dysphagia (PSD) face crucial challenges in taking oral medications due to swallowing difficulties, particularly with long-term secondary prevention medications. Current countermeasures relying on modification of existing formulations with thickened liquids carry potential hazards including bioavailability alterations and unsatisfactory safety profiles. Despite the obvious unfavorable impact, there is limited awareness and few effective solutions. Herein, an integrated patientcentered pharmaceutical framework to address critical oral medication challenges in PSD patients was established. A cross-sectional survey revealed that among Chinese stroke patients with stroke duration less than 5 years, 42.7% reported PSD. Among PSD participants, 40.2% frequently had difficulty swallowing pills, 37.1% regularly crushed solid oral dosage forms (SODFs), and 23.5% often coughed when taking SODFs, with 87.4% expressing need for PSD-specific formulations prioritizing safe and easy swallowing and reduced medication frequency. Driven by these patient-centered needs, a swallowing dynamics-inspired oleogel-in-hydrogel Pickering emulsion fluid gel was proposed as a versatile oral delivery system. With the dual structure of high acyl gellan gum (HAG) fluid gel and whey protein isolate (WPI) stabilized oleogel-in-hydrogel Pickering emulsion gel, the novel system demonstrated rheological properties wellmatched with swallowing dynamics, lower shear yield stress, better shear flowability, and superior extensional capabilities, alongside versatile loading potential for both hydrophilic and lipophilic substances. The customization capability of this biphasic fluid gel was further explored, confirming that microstructure and rheological properties could be tailored by adjusting HAG content and process mixing rate, enabling customization for different dysphagia severity levels referencing η50 based on NDD thickened fluid classification standards, with shear, extensional rheological capabilities and digestion rate aligning with expectations from mild to severe dysphagia. A patient self-controlled swallowing sensory evaluation study further validated significant improvements in swallowing experience across PSD cohorts with mild to severe dysphagia. Collectively, this work bridges patient-centered evidence with advanced pharmaceutical engineering, resolving swallowing challenges in long-term secondary prevention drug administration and establishing a transformative platform for PSD-specific oral drug delivery.