Emulsification-driven size control in supercritical PLGA-based encapsulation: from nanocapsules to microcapsules

Sustainable and adaptive technologies in drug delivery are essential in pharmaceutical engineering. This study explores supercritical emulsion extraction (SEE), a continuous and eco-efficient process that controls capsule morphology and enhances process efficiency. We investigated the impact of sonication steps, polymer co ncentration, and polylactic-co-glycolic acid (PLGA) molecular weight on capsule size and distribution. Two PLGA grades were tested: Resomer® RG 752 S (low molecular weight) and Resomer® RG 504H (high molecular weight). Modifying the sonication protocol allowed control over particle size: single sonication produced microcapsules (400–600 nm), for sustained gastrointestinal delivery or injectable formulations, while double sonication yielded nanoscale carriers (130–250 nm) for intracellular targeting and trans-barrier transport. Bromelain, an enzyme derived from agro-industrial waste, was used as a model bioactive compound, demonstrating high encapsulation efficiency and retained activity. Capsule size significantly influenced the release profile: nanocapsules exhibited rapid, diffusion-driven release, whereas microcapsules followed a biphasic pattern, initially governed by diffusion and later by polymer degradation and erosion. These findings aligned with Korsmeyer–Peppas kinetic model. SEE offers a versatile approach for producing tailored drug delivery platforms by adjusting internal processing steps, without altering system architecture. This method supports the development of greener, modular manufacturing pipelines for next-generation therapeutic systems. • Adaptive technology developed for customizable drug delivery systems. • Supercritical emulsion extraction used to control capsule morphology. • Sonication protocol shown to influence capsule size and distribution. • Bromelain encapsulated to study particle size impact on release profile. • Process tuning enables custom delivery without altering SEE core setup.