Sruti J, Patra Ch N, Swain S K, Beg S, Palatasingh H R, Dinda S C, Rao M E Bhanoji
Department of Pharmaceutics, Roland Institute of Pharmaceutical Sciences, Ambapua, Khodasingi, Berhampur 760 010, India.
Indian J Pharm Sci. 2013 Jan;75(1):67-75. doi: 10.4103/0250-474X.113551.
A combination of fusion and surface adsorption techniques was used to enhance the dissolution rate of cefuroxime axetil. Solid dispersions of cefuroxime axetil were prepared by two methods, namely fusion method using poloxamer 188 alone and combination of poloxamer 188 and Neusilin US2 by fusion and surface adsorption method. Solid dispersions were evaluated for solubility, phase solubility, flowability, compressibility, Kawakita analysis, Fourier transform-infrared spectra, differential scanning calorimetry, powder X-ray diffraction study, in vitro drug release, and stability study. Solubility studies showed 12- and 14-fold increase in solubility for solid dispersions by fusion method, and fusion and surface adsorption method, respectively. Phase solubility studies showed negative ΔG (0) tr values for poloxamer 188 at various concentrations (0, 0.25, 0.5, 0.75 and 1%) indicating spontaneous nature of solubilisation. Fourier transform-infrared spectra and differential scanning calorimetry spectra showed that drug and excipients are compatible with each other. Powder X-ray diffraction study studies indicated that presence of Neusilin US2 is less likely to promote the reversion of the amorphous cefuroxime axetil to crystalline state. in vitro dissolution studies, T50% and mean dissolution time have shown better dissolution rate for solid dispersions by fusion and surface adsorption method. Cefuroxime axetil release at 15 min (Q15) and DE15 exhibited 23- and 20-fold improvement in dissolution rate. The optimized solid dispersion formulation was stable for 6 months of stability study as per ICH guidelines. The stability was ascertained from drug content, in vitro dissolution, Fourier transform-infrared spectra and differential scanning calorimetry study. Hence, this combined approach of fusion and surface adsorption can be used successfully to improve the dissolution rate of poorly soluble biopharmaceutical classification system class II drug cefuroxime axetil.
采用熔融法和表面吸附技术相结合的方法来提高头孢呋辛酯的溶出速率。通过两种方法制备了头孢呋辛酯固体分散体，即单独使用泊洛沙姆188的熔融法，以及通过熔融和表面吸附法将泊洛沙姆188与纽西兰US2相结合的方法。对固体分散体进行了溶解度、相溶解度、流动性、可压性、河合分析、傅里叶变换红外光谱、差示扫描量热法、粉末X射线衍射研究、体外药物释放和稳定性研究。溶解度研究表明，通过熔融法和熔融及表面吸附法制备的固体分散体的溶解度分别提高了12倍和14倍。相溶解度研究表明，在不同浓度（0、0.25、0.5、0.75和1%）下，泊洛沙姆188的ΔG (0) tr值为负，表明溶解具有自发性。傅里叶变换红外光谱和差示扫描量热法光谱表明药物和辅料相互兼容。粉末X射线衍射研究表明，纽西兰US2的存在不太可能促进无定形头孢呋辛酯向结晶态的转变。体外溶出度研究表明，T50%和平均溶出时间显示，通过熔融和表面吸附法制备的固体分散体具有更好的溶出速率。头孢呋辛酯在15分钟时的释放量（Q15）和DE15的溶出速率提高了23倍和20倍。根据ICH指南，优化后的固体分散体制剂在6个月的稳定性研究中是稳定的。通过药物含量、体外溶出度、傅里叶变换红外光谱和差示扫描量热法研究确定了稳定性。因此，这种熔融和表面吸附相结合的方法可以成功地用于提高难溶性生物药剂学分类系统II类药物头孢呋辛酯的溶出速率。
