1 Department of Pharmaceutical Technology, Poznan University of Medical Sciences, Poznań, Poland.
2 Faculty of Chemistry, Adam Mickiewicz University in Poznań, Poznan, Poland.
J Biomater Appl. 2019 Apr;33(9):1214-1231. doi: 10.1177/0885328219830823. Epub 2019 Feb 21.
SBA-16 and two modified SBA-16 type ordered mesoporous silica were used as the carriers for ibuprofen (anti-inflammatory drug) and furosemide (loop diuretic drug). Modification of the solid carrier was prepared with chitosan or N-3[(amino(poly-propylenoxy)]aminopropyltrimethoxysilane. The samples of carriers and carrier-drug loaded materials were characterized by X-ray diffraction, N adsorption, Fourier-transform infrared spectroscopy, thermogravimetry, and differential scanning calorimetry. The release profiles of active pharmaceutical ingredients were performed in media with different pH in the USP 2 apparatus as well as in two biorelevant media (fasted state simulated gastric fluid and fasted state small intestinal fluid) in USP 4 apparatus. The loading of active substances into mesoporous materials was performed with modified immersion method. The maximum content of deposited drug in mesoporous material was close to 12.0 and 2.2 wt.% for ibuprofen and furosemide, respectively. After drug adsorption, the reduction of BET surface area, pore volume and pore diameter of non-modified and modified SBA-16 was observed, while the cubic arrays of siliceous matrix were well preserved. The release profiles of ibuprofen and furosemide loaded in mesoporous materials in media with different pH and biorelevant fasted state simulated gastric fluid and fasted state small intestinal fluid showed that the new SBA-16 type materials modify the release profiles of furosemide, increasing the dissolution rate of these substances in the medium at pH 1.2. The cytotoxicity of the materials and permeability of drugs after their loading on SBA-16 materials were evaluated on Caco-2 model. The results of our study showed that mesoporous materials did not exert cytotoxic effects and did not influence on the permeability of both active pharmaceutical ingredients in relation to pure substances.
SBA-16 和两种改性 SBA-16 型有序介孔硅作为布洛芬（抗炎药）和呋塞米（袢利尿剂）的载体。采用壳聚糖或 N-3[(氨基(聚丙氧基)]丙基三甲氧基硅烷对固体载体进行改性。载体和载药材料的样品通过 X 射线衍射、N 吸附、傅里叶变换红外光谱、热重分析和差示扫描量热法进行了表征。在 USP 2 装置中的不同 pH 介质以及 USP 4 装置中的两种生物相关介质（空腹模拟胃液和空腹小肠液）中进行了活性药物成分的释放曲线。采用改良浸渍法将活性物质载入介孔材料中。介孔材料中沉积药物的最大含量接近布洛芬和呋塞米的 12.0 和 2.2wt.%。吸附药物后，观察到未改性和改性 SBA-16 的 BET 表面积、孔体积和孔径减小，而硅质基质的立方阵列得到很好的保留。在不同 pH 介质和生物相关的空腹模拟胃液和空腹小肠液中载有布洛芬和呋塞米的介孔材料的释放曲线表明，新型 SBA-16 型材料改变了呋塞米的释放曲线，提高了这些物质在 pH 1.2 介质中的溶解速率。采用 Caco-2 模型评价了载药前后介孔材料的细胞毒性和药物渗透性。研究结果表明，介孔材料没有产生细胞毒性作用，也没有影响两种活性药物成分相对于纯物质的渗透性。
