Düzlü Ayşe Ünal, Günaydın Berrin, Şüküroğlu Murat Kadir, Değim İsmail Tuncer
Department of Anesthesiology and Reanimation, Gazi University School of Medicine, Ankara, Turkey.
Department of Pharmaceutical Chemistry, Gazi University School of Pharmacy, Ankara, Turkey.
Turk J Anaesthesiol Reanim. 2016 Feb;44(1):1-6. doi: 10.5152/TJAR.2016.02438. Epub 2016 Feb 1.
We aimed to compare the possible controlled release profile of multilamellar liposomal bupivacaine formulations with non-liposomal forms in artificial cerebrospinal fluid (CSF) under in vitro conditions.
Liposome formulations were prepared using a dry-film hydration method. Then, an artificial CSF-buffered solution was prepared. Bupivacaine base with liposomal bupivacaine base, bupivacaine HCl with liposomal bupivacaine HCl and bupivacaine HCl were added in a Franz diffusion cell. These solutions were kept in a hot water bath for 24 h. The samples were taken at 0.5, 1, 3, 6, 12 and 24 h (1st series of experiment). Solutions of bupivacaine base with liposomal bupivacaine base and bupivacaine HCl with liposomal bupivacaine HCl were centrifuged to obtain liposomal bupivacaine base and liposomal bupivacaine HCl. Afterwards, liposomal bupivacaine base and liposomal bupivacaine HCl were added in a Franz diffusion cell. After keeping these solutions in a hot water bath for 24 h as well, the samples were taken at the same time intervals (2(nd) series of experiment). All samples (54 from the 1st experiment and 36 from the 2(nd) experiment) were analysed with high-performance liquid chromatography and ultra-performance liquid chromatography and their chromatograms were obtained.
After obtaining calibration curves for bupivacaine base and HCl, release patterns of these formulations were plotted. A markedly controlled slow-release pattern was observed for multilamellar liposomal bupivacaine than for non-liposomal bupivacaine in artificial CSF.
Demonstration of controlled slow-release profile for mutilamellar liposomal bupivacaine in artificial CSF in vitro might support intrathecal use of liposomal bupivacaine in vivo in animal studies.
我们旨在比较多层脂质体布比卡因制剂与非脂质体形式在体外条件下于人工脑脊液（CSF）中的可能控释特性。
采用干膜水化法制备脂质体制剂。然后，制备人工脑脊液缓冲溶液。将布比卡因碱与脂质体布比卡因碱、盐酸布比卡因与脂质体盐酸布比卡因以及盐酸布比卡因加入弗兰兹扩散池。这些溶液在热水浴中放置24小时。在0.5、1、3、6、12和24小时取样（第一系列实验）。将布比卡因碱与脂质体布比卡因碱以及盐酸布比卡因与脂质体盐酸布比卡因的溶液离心以获得脂质体布比卡因碱和脂质体盐酸布比卡因。之后，将脂质体布比卡因碱和脂质体盐酸布比卡因加入弗兰兹扩散池。同样将这些溶液在热水浴中放置24小时后，在相同时间间隔取样（第二系列实验）。所有样品（第一实验54个，第二实验36个）用高效液相色谱和超高效液相色谱进行分析并获得色谱图结果：获得布比卡因碱和盐酸布比卡因的校准曲线后，绘制这些制剂的释放模式图。在人工脑脊液中观察到多层脂质体布比卡因的控释模式明显比非脂质体布比卡因缓慢。
体外人工脑脊液中多层脂质体布比卡因控释特性的证明可能支持脂质体布比卡因在动物研究体内鞘内使用。
