Uniform lactose microspheres with high crystallinity fabricated by micro-fluidic spray drying technology combined with post-treatment process

Crystalline lactose microparticles with uniform size and spherical shape are greatly desirable for various applications, but still challenging. Herein, uniform lactose microspheres with high crystallinity were fabricated via spray drying lactose/polyethylene glycol (200 Da) (PEG 200) combined with ethanol/water post-treatment process. The effects of feed solution composition and ethanol/water volume ratio on particle size, morphology, density, crystal property and hygroscopicity were investigated.

Highlights

Uniform lactose microspheres with high crystallinity (> 90%) were obtained.

Micro-fluidic spray drying technology combined with post-treatment was utilized.

PEG 200 was essential for the post-treated particles to remain uniform and spherical.

Water promoted the crystallinity and Lα·H₂O content of the post-treated particles.

“Micro-zone competitive dissolution-reprecipitation” was proposed.

The obtained spherical lactose/PEG 200 microparticles were partially crystallized (30-50%), exhibiting dominant crystal forms of anhydrous Lα and Lβ. After removing PEG 200 by ethanol/water, the resulting microparticles remained uniform and spherical with enhanced crystallinity (92.90 ± 1.40%), high Lα·H₂O content (68.57%) and ultra-low hygroscopicity (0.29%).

Possible mechanism of “micro-zone competitive dissolution-reprecipitation” was proposed to reveal the influence of PEG 200 and ethanol/water volume ratio on promoting crystallinity and maintaining spherical morphology of lactose microparticles. This work provides a promising and up-scalable way to manufacture spherical crystalline microparticles.

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Article information: Tiantian Jiang, Shen Yan, Shengyu Zhang, Quanyi Yin, Xiao Dong Chen, Winston Duo Wu,
Uniform lactose microspheres with high crystallinity fabricated by micro-fluidic spray drying technology combined with post-treatment process, Powder Technology, Volume 392, 2021. https://doi.org/10.1016/j.powtec.2021.07.059.