Shenyang Pharmaceutical University, No. 103 Wenhua Road, Shenyang, 110016, China.
Cancer Hospital of China Medical University, No. 44 Xiaoheyan Road, Shenyang, 110042, China.
AAPS PharmSciTech. 2023 Dec 26;25(1):7. doi: 10.1208/s12249-023-02717-2.
Ginkgolides are receptor antagonist of platelet activating factor with great clinical prospect, but its application is limited by its low solubility, short half-life and poor alkaline environment stability. It is difficult to solve these problems with a single drug delivery system. In this study, supersaturated self-nanoemulsifying gastric floating tablets of ginkgolides were developed through the combination of solid supersaturated self-nanoemulsifying drug delivery system (solid S-SNEDDS) and gastric retentive floating drug delivery system (GFDDS) to solve these problems of ginkgolides. Solid S-SNEDDS was prepared by D-optimal mixture design, normalization method and single factor experiment. The properties of solid-S-SNEDDS were studied by TEM, PXRD, FT-IR, SEM and in vitro drug release profile. Then, the optimal formulation of stomach floating tablet was obtained through single factor experiment and center composite design, followed by the study of in vitro release, model and mechanism of release, in vitro buoyancy and kinetics of erosion and swelling. PXRD and FT-IR showed that the drug in solid S-SNEDDS existed in an amorphous manner and formed hydrogen bond with excipients. The results showed that the cumulative release of GA and GB in the optimal tablets was 96.12% and 92.57% higher than the simple tablets within 12 h. The release mechanism of the tablet was skeleton erosion and drug diffusion. In 12 h, the optimal tablets can float stably in vitro and release the drug at a constant rate, with a cumulative release of more than 80%. In summary, the combination of SNEDDS and GFDDS is a promising means to solve the problems of ginkgolides.
银杏内酯是血小板激活因子的受体拮抗剂,具有广阔的临床前景,但由于其溶解度低、半衰期短和在碱性环境中稳定性差,其应用受到限制。单一的药物传递系统很难解决这些问题。在这项研究中,通过将固体超饱和自乳化药物传递系统(固体 S-SNEDDS)和胃滞留漂浮药物传递系统(GFDDS)相结合,开发了银杏内酯的超饱和自乳化胃漂浮片剂,以解决银杏内酯的这些问题。固体 S-SNEDDS 是通过 D-最优混合设计、归一化方法和单因素实验制备的。通过 TEM、PXRD、FT-IR、SEM 和体外药物释放曲线研究了固体 S-SNEDDS 的性质。然后,通过单因素实验和中心复合设计得到胃漂浮片的最佳处方,随后进行体外释放、释放模型和机制、体外漂浮和溶胀动力学研究。PXRD 和 FT-IR 表明,固体 S-SNEDDS 中的药物以无定形形式存在,并与赋形剂形成氢键。结果表明,在 12 h 内,最佳片剂中 GA 和 GB 的累积释放量分别比普通片剂高 96.12%和 92.57%。片剂的释放机制为骨架侵蚀和药物扩散。在 12 h 内,最佳片剂可以在体外稳定漂浮,并以恒定的速率释放药物,累积释放率超过 80%。总之,SNEDDS 和 GFDDS 的结合是解决银杏内酯问题的一种很有前途的手段。