Zhang Qian, Li Yongquan, Li Linghui, Cheng Yushan, Yu Fangkun, Li Rui, Hou Shuguang
State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, Sichuan, China.
Sichuan Purity Pharmaceutical Co., Ltd, Chengdu, 610041, Sichuan, China.
AAPS PharmSciTech. 2023 Mar 14;24(3):78. doi: 10.1208/s12249-023-02536-5.
Amorphous and crystalline active pharmaceutical ingredients (APIs) are both widely studied for pulmonary delivery. The past research mainly studied the impact of solid-state properties on pharmacokinetic attributes; however, the influence of solid-state properties on aerosolization performance was much less studied. This study aimed to investigate the different aerosolization performances of amorphous and crystalline curcumin (Cur) stabilized with L-leucine. Cur was spray-dried with different concentrations of L-leucine (0, 5, 20, 35, and 50%, w/w) as both solution-based and suspension-based formulations to acquire amorphous and crystalline Cur powders. The physicochemical properties of the spray-dried powders, including particle size, morphology, and solid-state characteristics, were studied. The aerosolization performance as well as dissolution properties were evaluated. It was found that 35% (w/w) L-leucine or above led to the formation of amorphous Cur in the spray-dried powders, and the amorphous Cur powders exhibited higher FPF (70.8%, with 50% L-leucine, w/w) than the crystalline Cur formulations with an FPF at 56.3% (with 50% L-leucine, w/w). In conclusion, with a high concentration of L-leucine (35% or above) in the formulations, amorphous Cur would exhibit higher aerosolization efficiency than crystalline Cur. However, with a low concentration of L-leucine (20% or less) in the formulations, crystalline Cur would be preferred for more enhanced consideration.
无定形和结晶形活性药物成分（APIs）在肺部给药方面都得到了广泛研究。过去的研究主要关注固态性质对药代动力学属性的影响；然而，固态性质对雾化性能的影响研究较少。本研究旨在考察用L-亮氨酸稳定的无定形和结晶形姜黄素（Cur）的不同雾化性能。将Cur与不同浓度（0、5、20、35和50%，w/w）的L-亮氨酸分别制成溶液型和混悬型制剂进行喷雾干燥，以获得无定形和结晶形Cur粉末。研究了喷雾干燥粉末的物理化学性质，包括粒径、形态和固态特征。评估了雾化性能以及溶解性能。结果发现，35%（w/w）及以上的L-亮氨酸会导致喷雾干燥粉末中形成无定形Cur，无定形Cur粉末的细颗粒分数（FPF）（50% L-亮氨酸，w/w时为70.8%）高于结晶形Cur制剂（50% L-亮氨酸，w/w时FPF为56.3%）。总之，制剂中L-亮氨酸浓度较高（35%及以上）时，无定形Cur的雾化效率高于结晶形Cur。然而，制剂中L-亮氨酸浓度较低（20%及以下）时，从更综合的考虑出发，结晶形Cur更具优势。
