Laboratory of Pharmaceutical Technology and Biopharmacy, CIRM, University of Liège, Liège 4000, Belgium.
Laboratory of Pharmaceutical Technology and Biopharmacy, CIRM, University of Liège, Liège 4000, Belgium.
Int J Pharm. 2023 Feb 25;633:122639. doi: 10.1016/j.ijpharm.2023.122639. Epub 2023 Jan 21.
The aims of this study were, firstly, to select an optimal lipid solid dispersion of cannabidiol among different lipid excipients (Gelucire® 50/13, 48/16, 44/14 and Labrasol®) and inorganic carriers (colloidal silica, Syloid® XDP and Neusilin® US2) through a screening plan. The enhancement of aqueous solubility of cannabidiol from a free-flowing powder with adequate drug content was obtained by mixing cannabidiol (20%) with Gelucire® 50/13 (40%; Gattefossé, France), both incorporated inside mesopores of mesoporous silica Syloid® XDP (40%; Grace, Germany). Secondly, we have studied the tableting properties of this selected dispersion through a Design of Experiments (DoE) by manufacturing tablets with other excipients with using a compression simulator (Styl'One® Evo, Medelpharm, France). The design of experiments included the percentage of lipid solid dispersion, of glidant, of lubricant and different compression forces. The dissolution efficiency, the drug content, the tensile strength and the ejection force were analyzed. The DoE showed that % of dispersion as well as compression forces were the main influential variables. An exit of lipid materials outside the mesopores of silica due to compression process has been highlighted, reflected by reduced tensile strength. This study showed the possibility of manufacturing tablets with lipid materials even if limitations have been highlighted. Indeed, the dispersion percentage must not exceed 27% and compression forces up to 13 kN are required to produce lipid tablets with optimal properties.
本研究的目的首先是通过筛选方案，从不同的脂质赋形剂（Gelucire®50/13、48/16、44/14 和 Labrasol®）和无机载体（胶体二氧化硅、Syloid®XDP 和 Neusilin®US2）中选择最优的大麻二酚脂质固体分散体。通过将大麻二酚（20%）与 Gelucire®50/13（40%；Gattefossé，法国）混合，获得具有足够药物含量的自由流动粉末的大麻二酚的水溶解度的提高，这两种物质都被包裹在介孔二氧化硅 Syloid®XDP（40%；Grace，德国）的介孔中。其次，我们通过使用压缩模拟器（Styl'One®Evo，Medelpharm，法国），用其他赋形剂制造片剂，通过实验设计（DoE）研究了这种选择的分散体的压片特性。实验设计包括脂质固体分散体、助流剂、润滑剂的百分比和不同的压缩力。分析了溶解效率、药物含量、拉伸强度和推出力。实验设计表明，分散体的百分比以及压缩力是主要的影响变量。由于压缩过程，脂质材料从二氧化硅的介孔中逸出，这反映在拉伸强度的降低上。这项研究表明，即使存在限制，也有可能用脂质材料制造片剂。事实上，分散体的百分比不得超过 27%，压缩力必须达到 13kN，才能生产出具有最佳性能的脂质片剂。
