Abstract：
The objective of the current study is to prepare amorphous solid dispersions (ASDs) containing piperine (PIP) by utilizing organic acid glycyrrhizic acid (GA) and inorganic disordered mesoporous silica 244FP (MSN/244FP) as carriers and to investigate their dissolution mechanism. The physicochemical properties of ASDs were characterized with scanning electron microscopy (SEM), powder X-ray diffraction (PXRD), and differential scanning calorimetry (DSC). Fourier transform infrared spectroscopy (FTIR) and one-dimensional proton nuclear magnetic resonance (1H NMR) studies collectively proved that strong hydrogen-bonding interactions formed between PIP and the carriers in ASDs. Additionally, molecular dynamic (MD) simulation was conducted to simulate and predict the physical stability and dissolution mechanisms of the ASDs. Interestingly, it revealed a significant increase in the dissolution of amorphous PIP in ASDs in in vitro dissolution studies. Rapid dissolution of GA in pH 6.8 medium resulted in the immediate release of PIP drugs into a supersaturated state, acting as a dissolution-control mechanism. This exhibited a high degree of fitting with the pseudo-second-order dynamic model, with an R2 value of 0.9996. Conversely, the silanol groups on the outer surface of the MSN and its porous nanostructures enabled PIP to display a unique two-step drug release curve, indicating a diffusion-controlled mechanism. This curve conformed to the Ritger-Peppas model, with an R2 > 0.9. The results obtained provide a clear evidence of the proposed transition of dissolution mechanism within the same ASD system, induced by changes in the properties of carriers in a solution medium of varying pH levels.
摘要：
本研究的目的是以有机酸甘草酸（GA）和无机无序介孔二氧化硅244FP（MSN/244FP）为载体，制备含胡椒碱（PIP）的无定形固体分散体（ASDs），并研究其溶解机理。用扫描电子显微镜(SEM)对ASD的理化性质进行了表征,粉末X射线衍射(PXRD),和差示扫描量热法(DSC)。傅里叶变换红外光谱（FTIR）和一维质子核磁共振（1HNMR）研究共同证明，PIP与ASD中的载体之间形成了强烈的氢键相互作用。此外,进行分子动力学（MD）模拟以模拟和预测ASD的物理稳定性和溶解机理。有趣的是,在体外溶出研究中，发现无定形PIP在ASD中的溶出明显增加。GA在pH6.8介质中的快速溶解导致PIP药物立即释放到过饱和状态,作为溶解控制机制。这表现出与伪二阶动态模型的高度拟合，R2值为0.9996。相反，MSN外表面的硅烷醇基团及其多孔纳米结构使PIP能够显示出独特的两步药物释放曲线，表明扩散控制机制。这条曲线符合Ritger-Peppas模型,R2>0.9。获得的结果提供了在同一ASD系统内提出的溶解机制转变的明确证据。由不同pH值的溶液介质中载体性质的变化引起。
