Nanocrystallization and Microencapsulation of Natural Pigments for Improved Dissolution and Stability

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.