College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, People's Republic of China.
Curr Drug Deliv. 2022;19(6):721-729. doi: 10.2174/1567201818666210729111646.
Traditional dosage forms of granisetron (GRN) decrease patient compliance associated with repeated drug administration because of the short half-life of the drug.
In this study, novel GRN-loaded Polylactic-co-glycolic Acid (PLGA) sustained-release microspheres were prepared for the first time via a dropping-in-liquid emulsification technique. The effects of various factors, such as pH of the outer phase, Tween 80, Polyvinyl Alcohol (PVA) concentrations, and hardening process, on the Encapsulation Efficiency (EE), Drug Loading (DL), and particle size of microspheres were extensively studied. The physicochemical properties, including drug release, surface morphology, crystallinity, thermal changes, and molecular interactions, were also studied.
GRN has a pH-dependent solubility and it exhibits a remarkably high solubility under acidic condition. The EE of the alkaline medium (pH 8) was higher than that of the acidic medium (pH 4.0). EE and DL decreased in the presence of Tween 80 in the outer phase, whereas EE significantly increased during hardening. The particle size of microspheres was not affected by PVA and Tween 80 concentrations, but it was influenced by PVA volume and hardening. X-ray diffraction and differential scanning calorimetry results showed that the physical state of the drug changed from a crystalline form to an amorphous form, thereby confirming that the drug was encapsulated into the PLGA matrix. Fourier transform-infrared spectroscopy confirmed that some molecular interactions occurred between the drug and the polymer. GRN-loaded PLGA microspheres showed sustained release profiles of over 90% on week 3.
GRN-loaded PLGA microspheres with sustained-release were successfully prepared, and they exhibited a relatively high EE without Tween 80 as an emulsifier and with the hardening process.
格拉司琼（GRN）的传统剂型由于药物半衰期短，需要多次给药，因此降低了患者的依从性。
本研究首次通过液滴内乳化技术制备了新型 GRN 载体制备载有聚乳酸-共-羟基乙酸（PLGA）的缓释微球。研究了外相 pH 值、吐温 80、聚乙烯醇（PVA）浓度和硬化过程等各种因素对微球包封效率（EE）、载药量（DL）和粒径的影响。还研究了微球的物理化学性质，包括药物释放、表面形态、结晶度、热变化和分子相互作用。
GRN 的溶解度随 pH 值变化而变化，在酸性条件下具有很高的溶解度。碱性介质（pH8）的 EE 高于酸性介质（pH4.0）。在外相存在吐温 80 的情况下，EE 和 DL 降低，而在硬化过程中 EE 显著增加。微球的粒径不受 PVA 和吐温 80 浓度的影响，但受 PVA 体积和硬化的影响。X 射线衍射和差示扫描量热法结果表明，药物的物理状态从结晶态变为无定形态，从而证实药物被包封到 PLGA 基质中。傅里叶变换红外光谱证实药物和聚合物之间发生了一些分子相互作用。GRN 载 PLGA 微球在第 3 周时显示出超过 90%的持续释放曲线。
成功制备了具有缓释作用的 GRN 载 PLGA 微球，在没有吐温 80 作为乳化剂且具有硬化过程的情况下，表现出相对较高的 EE。
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