School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, China.
School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, China.
Carbohydr Polym. 2019 Oct 15;222:114978. doi: 10.1016/j.carbpol.2019.114978. Epub 2019 Jun 7.
The objective of present study was to explore whether polysaccharide could be employed as potential crystal growth inhibitor and provides synergistic effect on the supersaturation maintaining of lovastatin (LOV) in combination of nucleation inhibitor. Soluplus (SOL) and hyaluronic acid (HA) were selected as the most effective nucleation and crystal growth inhibitor respectively. The interaction between SOL and HA was elucidated via characterizing the particle size, zeta potential, surface hydrophobicity, solvent relaxation time (T) and FT-IR. The supersaturated drug solution was spray dried into amorphous solid dispersion, then, the in vitro release, moisture uptake and physical stability were investigated. The synergistic effect between SOL and HA was dependent on drug concentration, drug/carrier and SOL/HA weight ratio, which facilitated both in vitro and in vivo performance. It was disclosed that HA could insert into SOL structure providing both electrostatic and steric stabilization. In conclusion, the combination of nucleation and crystal growth inhibitors is a promising approach for supersaturated drug delivery system.
本研究旨在探讨多糖是否可以作为潜在的晶体生长抑制剂，并与成核抑制剂联合使用，对洛伐他汀（LOV）的过饱和度维持起到协同作用。选用 Soluplus（SOL）和透明质酸（HA）分别作为最有效的成核和晶体生长抑制剂。通过考察粒径、Zeta 电位、表面疏水性、溶剂弛豫时间（T）和傅里叶变换红外光谱（FT-IR）来阐明 SOL 和 HA 之间的相互作用。将过饱和药物溶液喷雾干燥成无定形固体分散体，然后考察其体外释放、吸湿性和物理稳定性。SOL 和 HA 之间的协同作用取决于药物浓度、药物/载体和 SOL/HA 重量比，这有利于改善其体内外性能。结果表明，HA 可以插入 SOL 结构，提供静电和空间稳定作用。总之，将成核和晶体生长抑制剂相结合是一种很有前途的过饱和药物传递系统的方法。
