Mesoporous silica particles are attractive carriers for poorly soluble drugs whereby confinement of drugs in the mesopores leads to amorphization, which makes them potential carriers for enhanced oral delivery. However, interactions between the drug molecules and the silica surface can lead to incomplete drug release. The strength of the interaction depends on the silica surface chemistry, which varies as a function of pH, as well as on drug chemistry and ionization states. Herein, the adsorption and dissolution behavior of weakly basic drugs were evaluated as a function of pH to understand the impact of electrostatic interactions on the performance of mesoporous silica-based formulations. A higher adsorption was noted when the drug interacted with the silica surface via electrostatic interactions compared to hydrogen bonding. Higher adsorption, in turn, led to a lower extent of drug release. In two-stage release studies of drugs with pK_a values close to the intestinal pH, a shift from low to higher pH solutions resulted in a decrease in the solution concentration. Further investigations demonstrated that this was due to readsorption of the drug, initially released in the acidic medium when the pH was increased. Two-stage release studies were also coupled with mass transport measurements. Only a slight improvement in drug release due to simultaneous absorption across a membrane was observed, suggesting strong drug adsorption to the silica surface arising from favorable electrostatic interactions, which diminishes the effect of sink conditions provided by the absorptive environment. This study highlights that physiological parameters, such as solution pH, are important considerations when designing mesoporous silica-based formulations for poorly soluble drugs. It also underscores the importance of incorporating in vivo-relevant conditions in in vitro testing to better evaluate these complex formulations due to the notable effect of dissolution media on the release behavior.

中文翻译：

---

药物-二氧化硅静电相互作用对基于介孔二氧化硅的口服给药系统中药物释放的影响。

中孔二氧化硅颗粒是难溶药物的有吸引力的载体，因此药物在中孔中的封闭导致无定形，这使其成为增强口服递送的潜在载体。但是，药物分子与二氧化硅表面之间的相互作用可能导致药物释放不完全。相互作用的强度取决于二氧化硅表面化学性质（随pH的变化而变化）以及药物化学性质和电离状态。在此，将弱碱性药物的吸附和溶解行为作为pH的函数进行评估，以了解静电相互作用对介孔二氧化硅基制剂性能的影响。与氢键相比，当药物通过静电相互作用与二氧化硅表面相互作用时，吸附度更高。更高的吸附力 反过来导致较低程度的药物释放。在具有p的药物的两阶段释放研究中ķ_一当pH值接近肠道pH值时，从低pH值溶液到高pH值溶液的转变导致溶液浓度降低。进一步的研究表明，这是由于药物的重吸收所致，当pH升高时，该药物最初在酸性介质中释放。两阶段释放研究还与质量传输测量相结合。由于同时跨膜吸收，仅观察到药物释放的轻微改善，这表明由于有利的静电相互作用而导致药物对二氧化硅表面的强烈吸附，这减弱了由吸收环境提供的下沉条件的影响。这项研究强调，在为难溶性药物设计中孔二氧化硅基制剂时，生理参数（例如溶液的pH）是重要的考虑因素。