Purpose

The objective of the present study was to develop HP-β-cyclodextrin inclusion complex-based rapid orally disintegrating tablets of pitavastatin calcium by unique sublimation technique for enhancing solubility and dissolution profile of anti-lipidemic class II drug.

Methods

The inclusion complex was prepared by a physical mixing method containing HP-β-cyclodextrin and pitavastatin calcium. The inclusion complex formation between the guest and host was confirmed by molecular docking studies. The developed inclusion complex was further characterized using differential scanning calorimetry (DSC), Fourier transform-infrared spectroscopy (FT-IR), powder X-ray diffraction study (PXRD), and scanning electron microscopy studies. Fast orally disintegrating tablets of pitavastatin calcium inclusion complex were developed by a unique sublimation technique employing full factorial design (2⁴) using the Design Expert® software. Independent factors, namely, type of super disintegrants and sublimating agents at varying concentrations, were studied for effect on disintegration time, hardness of the tablet, and in vitro drug release.

Results

Molecular docking studies showed a score of −8.08. Optimized formulation containing 5% Ac-di-sol, 10% camphor showed hardness of about 3.37 ± 0.11 kg/cm², least disintegration time 15.31 ± 0.32 s, and highest in vitro drug release of 99.11 ± 0.23% at the end of 15 min.

Conclusion

The employed complexation method enhanced solubility and increased in vitro dissolution of pitavastatin calcium. It was concluded that fast orally disintegrating tablets containing inclusion complex gave desired characteristics which provided rapid onset of action by fast disintegration and could improve patient compliance.

中文翻译：

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基于HP-β-CD包合物的匹伐他汀钙快速口腔崩解片的研制与优化

目的

本研究的目的是通过独特的升华技术开发基于 HP-β-环糊精包合物的匹伐他汀钙快速口腔崩解片，以提高抗血脂 II 类药物的溶解度和溶出度。

方法

包合物通过物理混合法制备，含有HP-β-环糊精和匹伐他汀钙。通过分子对接研究证实了客体和宿主之间的包合物形成。使用差示扫描量热法 (DSC)、傅里叶变换红外光谱 (FT-IR)、粉末 X 射线衍射研究 (PXRD) 和扫描电子显微镜研究进一步表征了所开发的包合物。匹伐他汀钙包合物快速口腔崩解片是通过采用全因子设计的独特升华技术开发的（2 ⁴) 使用 Design Expert® 软件。研究了独立因素，即不同浓度的超级崩解剂和升华剂的类型，对崩解时间、片剂硬度和体外药物释放的影响。

结果

分子对接研究显示得分为-8.08。含 5% Ac-di-sol、10% 樟脑的优化配方显示硬度约为 3.37 ± 0.11 kg/cm ²，崩解时间最短为 15.31 ± 0.32 s，15 结束时体外药物释放最高为 99.11 ± 0.23%分钟。

结论

所采用的络合方法提高了匹伐他汀钙的溶解度和体外溶出度。得出的结论是，含有包合复合物的快速口腔崩解片剂具有所需的特性，通过快速崩解提供快速起效并可以提高患者的依从性。