Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Damascus University, Syria.
Saudi Pharm J. 2011 Oct;19(4):245-53. doi: 10.1016/j.jsps.2011.05.004. Epub 2011 May 23.
The current study aimed to prepare a sustained release tablet for a drug which has poor solubility in alkaline medium using complexation with cyclodextrin. Nicardipine hydrochloride (NC) a weak basic drug was chosen as a model drug for this study.
Firstly the most suitable binary system NC-HPβCD was selected in order to improve drug solubility in the intestinal media and then embedding the complexed drug into a plastic matrix, by fusion method, consists of glycerol monostearate (GMS) as an inert waxy substance and polyethylene glycol 4000 (PEG4000) as a channeling agent, after that the final solid dispersion [(NC:HPβCD):GMS:PEG4000] which was prepared at different ratios was mixed with other excipients, avicel PH101, lactose, and talc, to get a tablet owning dissolution profile complying with the FDA and USP requirements for the extended release solid dosage forms.
Infrared spectroscopy (IR), differential scanning colorimetry (DSC), polarized microscopy and X-ray diffractometry proved that the coevaporation technique was effective in preparing amorphous cyclodextrin complexes with NC and trapping of NC within the HPβCD cavity by dissolving both in ethanol and evaporate the solvent using a rotavapor at 65 °C. Dissolution profile of NC enhanced significantly in pH 6.8 from NC:HPβCD inclusion complex prepared by the rotavapor (t-test Student p < 0.05). The release of NC from tablet containing [(NC:HPβCD):GMS:PEG4000] [(1):0.75:0.5] (w/w/w) solid dispersion (F8) was complying with the FDA dissolution requirements for extended release dosage forms, and studying the kinetics of the release showed that the diffusional contribution is the major factor controlling the drug release from that formula.
The prepared waxy matrix tablet containing NC complexes with CD shows promising results as extended release tablets.
本研究旨在制备一种用于在碱性介质中溶解度差的药物的缓释片剂，方法是与环糊精络合。选择盐酸尼卡地平（NC）作为本研究的模型药物，它是一种弱碱性药物。
首先选择最合适的 NC-HPβCD 二元体系，以提高药物在肠道介质中的溶解度，然后将复合物嵌入到由甘油单硬脂酸酯（GMS）作为惰性蜡质物质和聚乙二醇 4000（PEG4000）作为通道剂的塑料基质中，然后将以不同比例制备的最终固体分散体[（NC：HPβCD）：GMS：PEG4000]与其他赋形剂混合，包括微晶纤维素 PH101、乳糖和滑石粉，以获得符合 FDA 和 USP 对延长释放固体剂型要求的溶出度曲线的片剂。
红外光谱（IR）、差示扫描量热法（DSC）、偏光显微镜和 X 射线衍射法证明，共蒸发技术有效地制备了与 NC 无定形环糊精络合物，并通过将两者溶解在乙醇中并在 65°C 下使用旋转蒸发器蒸发溶剂来将 NC 捕获在 HPβCD 腔室内。在 pH 6.8 下，通过旋转蒸发器制备的 NC：HPβCD 包合物（t 检验学生 p<0.05）显著增强了 NC 的溶解曲线。含有[（NC：HPβCD）：GMS：PEG4000] [（1）：0.75：0.5]（w/w/w）固体分散体（F8）的片剂中 NC 的释放符合 FDA 对延长释放剂型的释放要求，研究释放动力学表明扩散贡献是控制该配方中药物释放的主要因素。
含有 NC 与 CD 复合物的蜡质基质片剂作为缓释片剂具有广阔的前景。
