Mokhtar Mahmoud, Sammour Omaima A, Hammad Mohammed A, Megrab Nagia A
Department of Pharmaceutics, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt.
Int J Pharm. 2008 Sep 1;361(1-2):104-11. doi: 10.1016/j.ijpharm.2008.05.031. Epub 2008 Jun 3.
Proniosomal gels or solutions of flurbiprofen were developed based on span 20 (Sp 20), span 40 (Sp 40), span 60 (Sp 60), and span 80 (Sp 80) without and with cholesterol. Nonionic surfactant vesicles (niosomes) formed immediately upon hydrating proniosomal formulae. The entrapment efficiency (EE%) of flurbiprofen (a poorly soluble drug) was either determined by exhaustive dialysis of freshly prepared niosomes or centrifugation of freeze-thawed vesicles. The influence of different processing and formulation variables such as surfactant chain length, cholesterol content, drug concentration, total lipid concentration, negatively or positively charging lipids, and the pH of the dispersion medium on flurbiprofen EE% was demonstrated. Also, the release of the prepared niosomes in phosphate buffer (pH 7.4) was illustrated. Results indicated that the EE% followed the trend Sp 60 (C(18))>Sp 40 (C(16))>Sp 20 (C(12))>Sp 80 (C(18)). Cholesterol increased or decreased the EE% depending on either the type of the surfactant or its concentration within the formulae. The maximum loading efficiency was 94.61% when the hydrating medium was adjusted to pH 5.5. Increasing total lipid or drug concentration also increased the EE% of flurbiprofen into niosomes. However, incorporation of either dicetyl phosphate (DCP) which induces negative charge or stearyl amine (SA) which induces positive charge decreased the EE% of flurbiprofen into niosomal vesicles. Finally, in vitro release data for niosomes of Sp 40 and Sp 60 showed that the release profiles of flurbiprofen from niosomes of different cholesterol contents is an apparently biphasic release process. As a result, this study suggested the potential of proniosomes as stable precursors for the immediate preparation of niosomal carrier systems.
基于司盘20（Sp 20）、司盘40（Sp 40）、司盘60（Sp 60）和司盘80（Sp 80），分别在有无胆固醇的情况下制备了氟比洛芬前体脂质体凝胶或溶液。水合前体脂质体配方后立即形成非离子表面活性剂囊泡（脂质体）。氟比洛芬（一种难溶性药物）的包封率（EE%）通过对新制备的脂质体进行彻底透析或对冻融后的囊泡进行离心来测定。研究了不同加工和配方变量，如表面活性剂链长、胆固醇含量、药物浓度、总脂质浓度、带负电或正电的脂质以及分散介质的pH值对氟比洛芬EE%的影响。此外，还展示了所制备的脂质体在磷酸盐缓冲液（pH 7.4）中的释放情况。结果表明，EE%遵循Sp 60（C(18)）>Sp 40（C(16)）>Sp 20（C(12)）>Sp 80（C(18)）的趋势。胆固醇会根据表面活性剂的类型或其在配方中的浓度增加或降低EE%。当水合介质调节至pH 5.5时，最大负载效率为94.61%。增加总脂质或药物浓度也会提高氟比洛芬在脂质体中的EE%。然而，加入诱导负电荷的磷酸二鲸蜡酯（DCP）或诱导正电荷的硬脂胺（SA）会降低氟比洛芬在脂质体囊泡中的EE%。最后，Sp 40和Sp 60脂质体的体外释放数据表明，不同胆固醇含量的脂质体中氟比洛芬的释放曲线是一个明显的双相释放过程。因此，本研究表明前体脂质体作为脂质体载体系统即时制备的稳定前体具有潜力。
