Abstract
Natural lipophilic pigments typically exhibit poor water solubility, low dissolution rates, and photothermal instability, which hinder their pharmaceutical application. To address these challenges, a nanosuspension–microencapsulation delivery system was developed using curcumin (CUR) and lutein (LUT) as model compounds to enhance dissolution and stability. Hydroxypropyl methylcellulose E5 (HPMC-E5) was identified as the optimal stabilizer for CUR and LUT nanosuspensions (NS) prepared by antisolvent precipitation and optimized by wet media milling.
The resulting CUR-NS achieved a rapid dissolution of 93.29 ± 3.43% within 5 min compared with 26.71 ± 1.11% for raw CUR, while LUT-NS reached 85.13 ± 2.27% at 120 min versus 13.35 ± 1.32% for raw LUT. To enhance powder properties and stability, nanosuspensions were transformed into microcapsules via spray drying and bottom-spray fluidized bed coating, yielding drug loadings of 10–30%. The spray-dried CUR microcapsules exhibited poor flowability (angle of repose: 47°), which improved to 33° after surface modification with 3% colloidal silica. In contrast, CUR and LUT microcapsules prepared with sucrose-based cores via fluidized bed coating showed larger particle sizes, smoother surfaces, excellent flowability (angle of repose ~ 20°), and direct compression suitability.
Accelerated stability tests revealed 1.3- to fourfold improvements in resistance to heat, light, and humidity compared with the raw pigments. Furthermore, compressibility evaluations confirmed good tableting performance for all microcapsules. Overall, this study demonstrates a robust nanosuspension–microencapsulation strategy that markedly enhances the dissolution, stability, and processing performance of poorly soluble natural pigments, highlighting its promise for industrial formulation and application.
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Cai, Z., Gong, H., Li, S. et al. Nanocrystallization and Microencapsulation of Natural Pigments for Improved Dissolution and Stability. AAPS PharmSciTech 27, 89 (2026). https://doi.org/10.1208/s12249-026-03325-6
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