Department of Pharmacy, Air Force General Hospital of PLA, Beijing 100142, China; Pharmacy College, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
School of Biomedical Sciences, Huaqiao University, Quanzhou 362021, China.
Chin J Nat Med. 2016 Oct;14(10):757-768. doi: 10.1016/S1875-5364(16)30090-5. Epub 2016 Oct 31.
Herpetospermum caudigerum lignans (HTL), one of the potential drugs with anti-hepatitis B virus and hepatoprotective effects, has limited clinical applications because of poor aqueous solubility and low bioavailability. Both herpetrione (HPE) and herpetin (HPN) are the most abundant ingredients in HTL and exhibit weak acidity. The purpose of the present study was to produce dried preparations of HTL (composed of HPE and HPN) nanosuspensions (HTL-NS) with high redispersibility using lyophilization technology. The HTL-NS was prepared by utilizing precipitation-combined homogenization technology based on acid-base neutralization reactions, and critical formulation and process parameters affecting the characteristics of HTL-NS were optimized. The resultant products were characterized by particle size analysis, SEM, XRD, stability, solubility, dissolution and in vivo bioavailability. HTL-NS showed near-spherical-shaped morphology and the size was 243 nm with a narrow PDI value of 0.187. The dried preparations with a relatively large particle size of 286 nm and a PDI of 0.215 were achieved by using 4% (W/V) mannitol as cryoprotectants, and had a better stability at 4 or 25 °C for 2 months, compared to HTL-NS. In the in vitro test, the dried preparations showed markedly increased solubility and dissolution velocity. Besides, in the in vivo evaluation, it exhibited significant increases in AUC, CMRT and a decrease in T, compared to the raw drug. In conclusion, our results provide a basis for the development of a drug delivery system for poorly water-soluble ingredients with pH-dependent solubility.
海帕托斯佩鲁姆考迪杰鲁木脂素（HTL）是一种具有抗乙型肝炎病毒和保肝作用的潜在药物，由于其水溶性差和生物利用度低，其临床应用受到限制。海帕酮（HPE）和海帕因（HPN）是 HTL 中含量最丰富的成分，均表现出弱酸性。本研究旨在利用冷冻干燥技术制备具有高再分散性的 HTL（由 HPE 和 HPN 组成）纳米混悬剂（HTL-NS）。HTL-NS 是通过利用基于酸碱中和反应的沉淀-联合匀化技术制备的，优化了影响 HTL-NS 特性的关键配方和工艺参数。通过粒径分析、SEM、XRD、稳定性、溶解度、溶出度和体内生物利用度对所得产物进行了表征。HTL-NS 呈近球形形态，粒径为 243nm，PDI 值为 0.187。使用 4%（W/V）甘露醇作为保护剂可获得粒径相对较大（286nm）、PDI 为 0.215 的干燥制剂，与 HTL-NS 相比，在 4°C 或 25°C 下放置 2 个月稳定性更好。在体外试验中，干燥制剂表现出明显增加的溶解度和溶解速度。此外，在体内评价中，与原料药相比，其 AUC、CMRT 显著增加，T 显著降低。总之，我们的结果为开发具有 pH 依赖性溶解度的难溶性成分的药物传递系统提供了依据。
