Purpose

The present study is concerned with the formulation of compression coated tablets of deflazacort. Research aimed to formulate a novel delivery system, based on chronomodulated approach for the management of rheumatoid arthritis, which is a chronic inflammatory disorder following a circadian pattern.

Method

The formulation consisted of a fast disintegrating core tablet and compressed-coated layer of polymers that delayed the release of drug. The core tablets were prepared by directly compressing powder blend of drug substance, superdisintegrants, talc, magnesium stearate, and Avicel PH 101. In case of compressed-coated layer, three types of polymers (HPMC K4M, ethyl cellulose, and sodium alginate) were used to modify the release of drug from delivery system.

Result

Preliminary batches were prepared to determine the effect of HPMC K4M, ethyl cellulose, and sodium alginate on lag time of the compression coated tablets. The effect of concentrations of polymers on lag time was studied for the optimization of formulation. Optimization of formulation was carried out by employing Box-Behnken Design using Design Expert 7.0. The lag time obtained from optimized batch was found to be 363.33±5.77 min. Thus, by means of an appropriate combination of excipients and suitable technique, it was possible to formulate a delivery system in which lag time followed by immediate release of drug was obtained.

Conclusion

It was found that it is possible to formulate a chronotherapeutic delivery system in which the lag time and time-controlled release behavior of drug from compression-coated tablet could be modulated by varying the concentration of hydrophilic and hydrophobic polymers so that the release of drug could coordinate with the circadian pattern of disease.

中文翻译：

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Deflazacort 计时给药系统的设计开发与优化

目的

本研究涉及地氟扎可压缩包衣片剂的配方。研究旨在制定一种基于时间调节方法的新型递送系统，用于治疗类风湿关节炎，这是一种遵循昼夜节律模式的慢性炎症性疾病。

方法

该制剂由快速崩解的片芯和延缓药物释放的聚合物压缩包衣层组成。核心片剂通过直接压制原料药、超级崩解剂、滑石粉、硬脂酸镁和 Avicel PH 101 的粉末混合物制备。在压制包衣层的情况下，三种聚合物（HPMC K4M、乙基纤维素和海藻酸钠）是用于改变药物从递送系统的释放。

结果

制备初步批次以确定 HPMC K4M、乙基纤维素和海藻酸钠对压缩包衣片剂滞后时间的影响。研究了聚合物浓度对滞后时间的影响，以优化配方。使用 Design Expert 7.0 通过 Box-Behnken Design 进行配方优化。发现从优化批次获得的延迟时间为 363.33±5.77 分钟。因此，通过赋形剂和适当技术的适当组合，可以制定一种给药系统，在该系统中获得延迟时间，然后立即释放药物。

结论

研究发现，可以制定一种计时给药系统，其中药物从压缩包衣片剂中的延迟时间和时间控制释放行为可以通过改变亲水性和疏水性聚合物的浓度来调节，从而药物的释放可以与疾病的昼夜节律模式相协调。