Department of Pharmacy, Air Force General Hospital of PLA, Beijing 100142, China; Department of Pharmacy, Guangyuan Central Hospital, Guanyuan 628000, China.
Department of Pharmacy, Air Force General Hospital of PLA, Beijing 100142, China; Department of Pharmacy, Shuangliu District Maternal and Child Health Hospital, Chengdu 610075, China.
Chin J Nat Med. 2018 Jan;16(1):70-80. doi: 10.1016/S1875-5364(18)30031-1.
The present study was designed to improve storage stability and oral bioavailability of Ganneng dropping pills (GNDP) by transforming lignans of Herpetospermum caudigerum (HL) composed of herpetrione (HPE) and herpetin (HPN) into nanosuspension (HL-NS), the main active ingredient of GNDP, HL-NS was prepared by high pressure homogenization and lyophilized to transform into solid nanoparticles (HL nanoparticles), and then the formulated HL nanoparticles were perfused into matrix to obtain NS-GNDP by melting method. For a period of 3 months, the content uniformity, storage stability and pharmacokinetics test in vivo of NS-GNDP were evaluated and compared with regular GNDP at room temperature. The results demonstrated that uniformity of dosage units of NS-GNDP was acceptable according to the criteria of Chinese Pharmacopoeia 2015J. Physical stability of NS-GNDP was investigated systemically using photon correlation spectroscopy (PCS), zeta potential measurement, and scanning electron microscopy (SEM). There was a slight increase in particles and PI of HL-NS re-dispersed from NS-GNDP after storage for 3 months, compared with new formulated NS-GNDP, which indicated a good redispersibility of the NS-GNDP containing HL-NS after storage. Besides, chemical stability of NS-GNDP was studied and the results revealed that HPE and HPN degradation was less when compared with that of GNDP, providing more than 99% of drug residue after storage for 3 months. In the dissolution test in vitro, NS-GNDP remarkably exhibited an increased dissolution velocity compared with GNDP and no distinct dissolution difference existed within 3 months. The pharmacokinetic study showed that HPE and HPN in NS-GNDP exhibited a significant increase in AUC, C and decrease in T when compared with regular GNDP. These results indicated that NS-GNDP possessed superiority with improved storage stability and increased dissolution rate and oral bioavailability.
本研究旨在通过将构成甘能滴丸（GNDP）主要活性成分的贯叶金丝桃（HL）中的木脂素类化合物（HL）转化为纳米混悬液（HL-NS），来提高 HL 的储存稳定性和口服生物利用度。HL-NS 是通过高压均质化和冷冻干燥制备的，转化为固体纳米颗粒（HL 纳米颗粒），然后将配制好的 HL 纳米颗粒灌注到基质中，通过熔融法获得 NS-GNDP。在室温下，对 NS-GNDP 的含量均匀性、储存稳定性和体内药代动力学试验进行了 3 个月的评估，并与常规 GNDP 进行了比较。结果表明，根据 2015J 年版《中国药典》的标准，NS-GNDP 的单位剂量均匀度是可以接受的。通过光相关光谱（PCS）、zeta 电位测量和扫描电子显微镜（SEM）系统地研究了 NS-GNDP 的物理稳定性。与新配制的 NS-GNDP 相比，储存 3 个月后从 NS-GNDP 重新分散的 HL-NS 的颗粒和 PI 略有增加，这表明储存后含有 HL-NS 的 NS-GNDP 具有良好的再分散性。此外，还研究了 NS-GNDP 的化学稳定性，结果表明，与 GNDP 相比，HPE 和 HPN 的降解较少，储存 3 个月后仍有超过 99%的药物残留。在体外溶出度试验中，与 GNDP 相比，NS-GNDP 显著提高了溶出速度，在 3 个月内没有明显的溶出差异。药代动力学研究表明，与常规 GNDP 相比，NS-GNDP 中的 HPE 和 HPN 的 AUC、C 显著增加，T 显著降低。这些结果表明，NS-GNDP 具有改善的储存稳定性、增加的溶解速率和口服生物利用度的优势。
