Reprecipitation-mediated regulation on the surface architecture of uniform spray dried lactose microspheres

Lactose microspheres (LMs) are commonly used in the pharmaceutical field. Although the surface architecture of LMs directly correlates with the performance of the final products, surface manipulation remains challenging. In this study, uniform LMs were fabricated using template-assisted spray drying with polyethylene glycol 200 as the template. The influence of the solvent composition (methanol, ethanol, 1-butanol, and acetone, with and without added water) and post-treatment parameters (time and temperature) on the moisture content, particle morphology, surface architecture, and crystal polymorphism were investigated. The sample surfaces post-treated using methanol were covered with particulate crystals with a crystallinity of ∼88.3 %, whereas those treated using acetone were covered by coral-like crystals with a crystallinity of ∼80.6 %. This is attributed to the higher solubility of lactose in methanol than in acetone. Adding a small amount of water to the post-treatment solvent facilitated amorphous lactose reprecipitation, achieving a block-like crystal stacking surface with a more stable Lα∙H2O content (∼40.4 % w/w). Lα∙H2O enriched on the LM surfaces prevents water absorption during storage, thus maintaining their high dispersity, uniformity, and surface architecture. This study provides a promising strategy for tailoring the surface architecture of spherical crystalline lactose microspheres. [Display omitted] •Uniform LMs are fabricated via template-assisted spray drying.•PEG 200 is removed during post-treatment, preserving spherical morphology.•Solvent with higher lactose solubility increases crystallinity, etching surface.•Adding water promotes the formation of more stable Lα·H2O.•Stable Lα·H2O on particle surface enhances storage stability.