Formulation and evaluation of 5-fluorouracil controlled release chronotherapeutic drug delivery system (CTDDS) for colorectal cancer

Hammad Ayaz, Muhammad Ahmad, Mustafa Kazmi, Husnain Ahmed, Talib Hussain, Ishtiaq Jeelani, Ume Habiba, Muhammad Akram Choohan
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Abstract

Objective: As most of the drugs disintegrate and dissolve in stomach before reaching the target site and to substitute intravenous (IV) route based chrono modulated chemotherapy, oral colon target drug delivery system was formed. The aim of this study was to design, develop, and evaluate a colon targeted tablet containing 5-Fluorouracil (5-FU) to give a controlled release effect of drug for colonic cancer with a goal to increase the bioavailability and improve the patient compliance. Methods: Varied concentration of different polymers such as Xanthan gum and Eudragit were used to get an optimized formulation of 5-FU tablet. The prepared formulation was evaluated for pre compression and post compression parameters such as hardness, weight, friability and drug content uniformity. The optimized formulation was further evaluated by Fourier Transformed Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), in-vitro dissolution studies, dissolution kinetic modeling and stability analysis. Results: All pre-formulation tests were within range of USP standards. Friability of all tablets was satisfied. The interference of the polymers was ruled out by FTIR. In-vitro release studies of 5-FU tablets in phosphate buffer of pH 7.0 were performed using a modified diffusion cell that resulted sustained release (90.99% to 92.69% after 12h) and kinetic models depicted the combined diffusion and dissolution mechanism of release. The optimized tablets were found having only physical interactions based on DSC. The product was found stable when evaluated using accelerated stability studies. Conclusion: It was concluded from the studies that the colon target tablet of 5-FU prepared by different concentration of polymers were optimized and can be efficiently used to control the rate of drug release to the colon in the belief of improved therapeutic efficacy and tolerability. Therefore, it is a better alternative for intravenous route based chrono modulated chemotherapy.
结直肠癌5-氟尿嘧啶控释缓释药物缓释系统的研制与评价
目的:由于药物在到达靶部位前大多在胃内崩解溶解,替代静脉(IV)途径为主的时间调节化疗,形成口服结肠靶向给药体系。本研究旨在设计、开发和评价含5-氟尿嘧啶(5-FU)结肠靶向片剂对结肠癌的控释作用,以提高药物的生物利用度和患者的依从性。方法:采用不同浓度的黄原胶、乌桕脂等不同聚合物,优选5-FU片的最佳配方。对制备的制剂进行了硬度、重量、易碎性、药物含量均匀性等压缩前后参数的评价。通过傅里叶红外光谱(FTIR)、差示扫描量热法(DSC)、体外溶出度研究、溶出动力学建模和稳定性分析对优化后的配方进行了进一步的评价。结果:制剂前试验均在USP标准范围内。所有片剂的易碎性均满足要求。FTIR排除了聚合物的干扰。采用改进的扩散池对5-FU片在pH 7.0的磷酸盐缓冲液中的体外释放进行了研究,获得了12h缓释(90.99% ~ 92.69%)的效果,并建立了扩散-溶出联合释放的动力学模型。DSC结果表明,优化后的片剂仅存在物理相互作用。当使用加速稳定性研究评估时,发现该产品是稳定的。结论:通过研究,优化了不同浓度聚合物制备的5-FU结肠靶片,可以有效地控制药物到结肠的释放速度,提高了治疗效果和耐受性。因此,它是基于静脉途径的时间调节化疗的较好选择。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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