Department of Pharmaceutical Quality Assurance, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, India.
Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education & Research (NIPER) Guwahati, Guwahati, India.
Drug Dev Ind Pharm. 2022 Jun;48(6):227-238. doi: 10.1080/03639045.2022.2104308. Epub 2022 Jul 27.
Raloxifene HCl (RLX), a practically insoluble drug used in the treatment of osteoporosis in post-menopausal women; was modified at its molecular level to enhance its solubility using co-amorphous technology.
In this study, RLX was co-amorphized with Quercetin (QCT; a nutraceutical flavonoid) using solvent evaporation (SE), quench cooling (QC), and ball milling (BM) techniques. The prepared co-amorphous systems (CAMs) were characterized using XRD, DSC, and FT-IR. For the simultaneous analysis of RLX and QCT, an RP-HPLC method was developed to quantify the drugs in the prepared systems. Behavior in aqueous media was investigated by studying amorphous and equilibrium solubility, and drug release of RLX using USP phosphate buffer pH 6.8.
Solvent evaporation (RQ(SE)) was able to produce a homogeneous system, where quench cooling showed thermal degradation of the drug, and ball milling was not able to amorphize the blend. From the DSC results, it was found that RQ(SE) was able to increase the glass transition temperature by 40 °C. It was observed that the solubility of RLX reduced, as RLX formed phosphate aggregates in the buffer media which further formed complexes with QCT; this was determined by investigating the residual particles from solubility studies. Though the solubility was reduced, drug release of RQ(SE) exhibited improvement in concentration by 2.3 times.
RQ(SE) formed a stable CAM; though the solubility of RLX in presence of QCT reduced, from the drug release study, it was apparent that the co-amorphous technique improved the concentration of RLX.
盐酸雷洛昔芬（RLX）是一种在绝经后妇女骨质疏松症治疗中使用的几乎不溶的药物；通过分子水平修饰，使用共无定形技术来提高其溶解度。
在这项研究中，RLX 与槲皮素（QCT；一种营养类黄酮）通过溶剂蒸发（SE）、骤冷（QC）和球磨（BM）技术共无定形化。使用 XRD、DSC 和 FT-IR 对制备的共无定形系统（CAM）进行了表征。为了同时分析 RLX 和 QCT，开发了一种 RP-HPLC 方法来定量测定制备系统中的药物。通过研究 RLX 的无定形和平衡溶解度以及在 USP 磷酸盐缓冲液 pH6.8 中的药物释放来研究在水介质中的行为。
溶剂蒸发（RQ（SE））能够产生均匀的系统，其中骤冷显示药物热降解，而球磨不能使混合物无定形。从 DSC 结果发现，RQ（SE）能够将玻璃化转变温度提高 40°C。观察到 RLX 的溶解度降低，因为 RLX 在缓冲介质中形成磷酸盐聚集体，这些聚集体进一步与 QCT 形成配合物；这是通过研究溶解度研究中的残留颗粒来确定的。尽管溶解度降低，但 RQ（SE）的药物释放显示浓度提高了 2.3 倍。
RQ（SE）形成了稳定的共无定形物；尽管 QCT 存在时 RLX 的溶解度降低，但从药物释放研究中可以明显看出，共无定形技术提高了 RLX 的浓度。
