PREPARATION PROCESS FOR ORAL DISSOLVING FILM OF GINKGOLIDE B FOR TREATMENT OF ALZHEIMER'S DISEASE

Juntong Zhou*, Qinmei Xu*, Yue Wang*, **, Zhenpeng Wang***, Jiayang Li****, Shan Yu*, Kexin Liu*, Chi Li*, Shuhui Li*, Yuan Zhang*, Xintong Qu*, Ye Tian*, Zhaoxuan Feng*, Qing Huo*, **,#

*Biochemical Engineering College, Beijing Union University, Beijing, P. R. China - **Beijing Key Laboratory of Biomass Waste Resource Utilization, Beijing, P. R. China - ***Institute of Chemistry, Chinese Academy of Sciences, Beijing, P.R. China - ****CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety & CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing, China

Objective: Ginkgolide B (GB) has been applied to cardiovascular diseases in clinic with its anti-oxidative and anti-aging effects. GB plays a neuroprotective role in models of various diseases. A study showns that Aβ1-42 induces oxidative damage to the cellular biomolecules, which are associated with AD pathology, and are protected by the pre-treatment of GB against Aβ-toxicity. We prepared the oral dissolving film (ODF) of GB by tape casting. The influence of film forming material, plasticizer and defoamer on the performance of the ODF of GB was studied. ODF has better adherence and is easy to take, which provides certain reference value for future nerve agents.

Methods: The preparation parameters were as follows: 35mg GB was dissolved with 70ml of distilled water and mixed well, which was followed by the addition of 0.5g of glycerol as the plasticizer. After complete dissolution, 2g of hydroxypropyl methylcellulose was added as the film forming material. An ODF solution was formed by mixing, during which two to three drops of edible defoamer were added. After defoaming, the solution was coated onto the carrier sheet and left to stand until complete drying. Then the film was cut into a proper size. 

Results: Experiments showed that the ODF of GB could completely dissolve in 280s and 80% of GB was released in 1min. The degree of release reached100% in 3min. This drug was pasted onto the supralingual area of 0.6×1.3mm with a single dose of 1mg/kg for the rats. Pharmacokinetic parameters were measured, and the clearance rate CL (L/h) was calculated as 2.156, Cmax (ng•mL-1): 13.52, Tmax: 4h.

Conclusion: The AUC for the ODF of GB was larger by about 1.77-fold as compared with the intragastric administration of GB. The bioavailability of ODF of the drug was higher than other conventional oral preparations.