Mudrić Jelena, Đekić Ljiljana, Krgović Nemanja, Medarević Đorđe, Šavikin Katarina, Radan Milica, Ćujić Nikolić Nada, Ilić Tijana, Vidović Bojana, Đuriš Jelena
Institute for Medicinal Plants Research "Dr. Josif Pančić", 11000 Belgrade, Serbia.
Faculty of Pharmacy, University of Belgrade, 11221 Belgrade, Serbia.
Pharmaceutics. 2025 Jan 7;17(1):71. doi: 10.3390/pharmaceutics17010071.
This study aimed to develop gastroretentive tablets based on mucoadhesive-floating systems with encapsulated gentian (, Gentianaceae) root extract to overcome the low bioavailability and short elimination half-life of gentiopicroside, a dominant bioactive compound with systemic effect. The formulation also aimed to promote the local action of the extract in the stomach. Tablets were obtained by direct compression of sodium bicarbonate (7.5%) and solid lipid microparticles (92.5%), which were obtained with lyophilizing double emulsions. A quality by design (QbD) was employed to evaluate the impact of formulation factors and processing parameters on emulsion viscosity, powder characteristics (moisture content, encapsulation efficiency, flowability), and tablet characteristics (floating lag time, gentiopicroside release, and assessment of dispersibility during in vitro dissolution). The trehalose content and high-shear-homogenization (HSH) time of primary emulsion were critical factors. Trehalose content positively influenced emulsion viscosity, moisture content, floating lag time, encapsulation efficiency, and the release rate of gentiopicroside. HSH time positively affected powder stability and negatively gentiopicroside release. The selected powder had a high gentiopicroside encapsulation efficiency (95.13%), optimal stability, and good flowability. The developed tablets exhibited adequate floating lag time (275 s), mucoadhesive properties, and gentiopicroside biphasic release (29.04% in 45 min; 67.95% in 6 h). Furthermore, the optimal tablet formulation remained stable for 18 months and was primarily digested by duodenal enzymes. Dual-mechanism gastroretentive tablets with encapsulated gentian root extract were successfully developed. The in vitro digestion study demonstrated that the optimal formulation effectively resisted gastric enzymes, ensuring the release of its contents in the small intestine, even in the case of premature gastric evacuation.
本研究旨在开发基于黏膜黏附-漂浮系统的胃滞留片，其中包封龙胆（龙胆科）根提取物，以克服龙胆苦苷生物利用度低和消除半衰期短的问题，龙胆苦苷是一种具有全身作用的主要生物活性化合物。该制剂还旨在促进提取物在胃中的局部作用。通过直接压片法将碳酸氢钠（7.5%）和固体脂质微粒（92.5%）制成片剂，固体脂质微粒通过冻干复乳法制得。采用质量源于设计（QbD）方法评估制剂因素和工艺参数对乳液黏度、粉体特性（水分含量、包封率、流动性）以及片剂特性（漂浮滞后时间、龙胆苦苷释放度和体外溶出过程中的分散性评估）的影响。初级乳液的海藻糖含量和高剪切均质化（HSH）时间是关键因素。海藻糖含量对乳液黏度、水分含量、漂浮滞后时间、包封率以及龙胆苦苷释放速率有正向影响。HSH时间对粉体稳定性有正向影响，对龙胆苦苷释放有负向影响。所选粉体具有较高的龙胆苦苷包封率（95.13%）、最佳稳定性和良好的流动性。所开发的片剂表现出适当的漂浮滞后时间（275秒）、黏膜黏附特性以及龙胆苦苷双相释放（45分钟内释放29.04%；6小时内释放67.95%）。此外，最佳片剂配方在18个月内保持稳定，且主要由十二指肠酶消化。成功开发了包封龙胆根提取物的双机制胃滞留片。体外消化研究表明，即使在胃排空过早的情况下，最佳配方也能有效抵抗胃酶，确保其内容物在小肠中释放。
