Ishtiaq Memoona, Manzoor Hina, Khan Ikram Ullah, Asghar Sajid, Irfan Muhammad, Albekairi Norah A, Alshammari Abdulrahman, Alqahtani Abdulrahman F, Alotaibi Saad, Munir Rabia, Shah Pervaiz A, Hussain Liaqat, Saleem Muhammad Abubakar, Razzaq Fizza Abdul, Khalid Syed Haroon
Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Government College University, Faisalabad 38000, Pakistan.
Faculty of Pharmaceutical Sciences, Government College University, Faisalabad 38000, Pakistan.
Heliyon. 2024 Jul 14;10(14):e34636. doi: 10.1016/j.heliyon.2024.e34636. eCollection 2024 Jul 30.
Amorphous solid dispersion (ASD) has emerged to be an outstanding strategy among multiple options available for improving solubility and consequently biological activity. Interestingly several binary SD systems continue to exhibit insufficient solubility over time. Therefore, the goal of current research was to design ternary amorphous solid dispersions (ASDs) of hydrophobic model drug curcumin (CUR) to enhance the solubility and dissolution rate in turn, presenting enhanced anti-bacterial, antioxidant and anti-inflammatory activity. For this purpose several ternary solid dispersions (TSDs) consisting of Soluplus®, Syloid® XDP 3150, Syloid® 244 and Poloxamer® 188 in combination with HPMC E5 (binary carrier) were prepared using solvent evaporation method. Both solubility and dissolution testing of prepared solid dispersion were performed to determine the increase in solubility and dissolution. Solid state investigation was carried out utilizing infrared spectroscopy, also known as Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM),Differential scanning calorimetry (DSC) and X-ray diffraction (XRD).Optimized formulations were also tested for their biological effectiveness including anti-bacterial, anti-oxidant and anti-inflammatory activity. Amid all Ternary formulations F3 entailing 20 % soluplus® remarkably improved the solubility (186 μg/ml ± 3.95) and consequently dissolution (91 % ± 3.89 %) of curcumin by 3100 and 9 fold respectively. These finding were also supported by FTIR, SEM, XRD and DSC. In-vitro antibacterial investigation of F3 also demonstrated significant improvement in antibacterial activity against both gram positive ( and gram negative (, bacteria. Among all the tested strains was found to be most susceptible with a zone of inhibition of 24 mm ± 2.87. Antioxidant activity of F3 was also notably enhanced (93 % ± 5.30) in contrast to CUR (69 % ± 4.79). In vitro anti-inflammatory assessment also exhibited that F3 markedly protected BSA (bovine serum albumin) from denaturation with percent BSA inhibition of 80 % ± 3.16 in comparison to CUR (49 % ± 2.91). Hence, F3 could be an effective solid dispersion system for the delivery of model hydrophobic drug curcumin.
无定形固体分散体（ASD）已成为多种提高溶解度从而提高生物活性的方法中一种出色的策略。有趣的是，随着时间的推移，几种二元固体分散体系统的溶解度仍然不足。因此，当前研究的目标是设计疏水性模型药物姜黄素（CUR）的三元无定形固体分散体（ASD），以依次提高其溶解度和溶出速率，呈现出增强的抗菌、抗氧化和抗炎活性。为此，使用溶剂蒸发法制备了几种由固体分散体（Soluplus®）、Syloid® XDP 3150、Syloid® 244和泊洛沙姆® 188与羟丙甲纤维素E5（二元载体）组合而成的三元固体分散体（TSD）。对制备的固体分散体进行溶解度和溶出度测试，以确定溶解度和溶出度的增加情况。利用红外光谱（也称为傅里叶变换红外光谱（FTIR））、扫描电子显微镜（SEM）、差示扫描量热法（DSC）和X射线衍射（XRD）进行固态研究。还对优化后的制剂进行了生物有效性测试，包括抗菌、抗氧化和抗炎活性。在所有三元制剂中，含有20%固体分散体（Soluplus®）的F3显著提高了姜黄素的溶解度（186μg/ml±3.95），从而使溶出度（91%±3.89%）分别提高了3100倍和9倍。这些发现也得到了FTIR、SEM、XRD和DSC的支持。F3的体外抗菌研究还表明，其对革兰氏阳性菌和革兰氏阴性菌的抗菌活性有显著提高。在所有测试菌株中，发现[具体菌株名称]最敏感，抑菌圈为24mm±2.87。与姜黄素（69%±4.79）相比，F3的抗氧化活性也显著增强（93%±5.30）。体外抗炎评估还表明，与姜黄素（49%±2.91）相比，F3能显著保护牛血清白蛋白（BSA）不发生变性，BSA抑制率为80%±3.16。因此，F3可能是一种有效的固体分散体系统，用于递送模型疏水性药物姜黄素。
