Cancer is the leading cause of mortality worldwide. In patients with metastatic non-small cell lung cancer, epidermal growth factor receptor (EGFR) is often overexpressed. Gefitinib (GEF), an inhibitor of EGFR, is approved for the treatment of patients with metastatic non-small cell lung cancer (NSCLC). However, the low solubility and dissolution of GEF limits its bioavailability. Numerous methods, including solid dispersion (SD) and complexation, have been reported to enhance the dissolution of poorly soluble drugs. In this study, GEF complexes were prepared using methyl-β-cyclodextrin (MβCD) and hydroxypropyl-β-cyclodextrin (HPβCD) in two molar ratios (1:1 and 1:2), furthermore, GEF SDs were prepared using polyvinylpyrrolidone (PVP), polyethylene glycol (PEG), and poloxamer-188(PXM) in three different ratios (1:2, 1:4 and 1:6 w/w). Dissolution studies were conducted on the prepared formulations. Dissolution results showed a 1.22–2.17-fold enhancement in drug dissolution after one hour compared to untreated GEF. Two formulations that showed higher dissolution enhancement were subsequently evaluated for in-vitro cytotoxicity and were formulated into tablets. The selected PVP–GEF (1:4 w/w) and MβCD–GEF (1:1M) formulas displayed improved cytotoxicity compared to untreated GEF. The IC values of the PVP–GEF and MβCD–GEF were 4.33 ± 0.66 and 4.84 ± 0.38 µM, respectively which are significantly lower (p < 0.05) than free GEF. In addition, the formulated tablets exhibited enhanced dissolution compared to pure GEF tablets. PVP–GEF SD tablets released (35.1 %.4) of GEF after one hour, while GEF-MβCD tablets released (42.2 % after one hour. In the meantime, tablets containing pure GEF showed only 15 % 0.5 release at the same time. The findings of this study offer valuable insights for optimizing the dissolution and hence therapeutic capabilities of GEF while mitigating its limitations.

中文翻译：

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通过固体分散体和与 β-环糊精络合增强吉非替尼的溶出度：体外测试、细胞毒活性和片剂配方

癌症是全世界死亡的主要原因。在转移性非小细胞肺癌患者中，表皮生长因子受体（EGFR）通常过度表达。吉非替尼 (GEF) 是一种 EGFR 抑制剂，被批准用于治疗转移性非小细胞肺癌 (NSCLC) 患者。然而，GEF的低溶解度和溶出度限制了其生物利用度。据报道，许多方法，包括固体分散体（SD）和络合，都可以增强难溶性药物的溶出度。在本研究中，使用甲基-β-环糊精（MβCD）和羟丙基-β-环糊精（HPβCD）以两种摩尔比（1：1和1：2）制备GEF复合物，此外，使用聚乙烯吡咯烷酮（PVP）制备GEF SD )、聚乙二醇 (PEG) 和 poloxamer-188(PXM)，以三种不同的比例（1:2、1:4 和 1:6 w/w）。对制备的制剂进行溶出度研究。溶出度结果显示，与未经处理的 GEF 相比，一小时后药物溶出度提高了 1.22–2.17 倍。随后评估了两种显示出更高溶出度增强的制剂的体外细胞毒性，并将其配制成片剂。与未经处理的 GEF 相比，所选的 PVP-GEF (1:4 w/w) 和 MβCD-GEF (1:1M) 配方显示出更好的细胞毒性。 PVP-GEF 和 MβCD-GEF 的 IC 值分别为 4.33 ± 0.66 和 4.84 ± 0.38 µM，明显低于游离 GEF（p < 0.05）。此外，与纯 GEF 片剂相比，配制的片剂表现出增强的溶出度。 PVP-GEF SD 片剂一小时后释放 (35.1 %.4) GEF，而 GEF-MβCD 片剂一小时后释放 (42.2 %)。同时，含有纯 GEF 的片剂同时仅释放 15 % 0.5。这项研究的结果为优化 GEF 的溶出度和治疗能力，同时减轻其局限性提供了宝贵的见解。