Obaidat Rana M, Tashtoush Bassam M, Awad Alaa Abu, Al Bustami Rana T
Department of Pharmaceutical Technology, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan.
Pharmaceutical Research Unit, Amman, Jordan.
AAPS PharmSciTech. 2017 Feb;18(2):481-493. doi: 10.1208/s12249-016-0492-4. Epub 2016 Apr 26.
Tacrolimus is an immunosuppressant agent that suffers from poor and variable bioavailability. This can be related to limited solubility and dissolution. The main objective of this study is to use SFT to prepare solid dispersions of tacrolimus in order to enhance its dissolution. SFT was selected since it offers several advantages over conventional techniques such as efficiency and stability. Several solid dispersions of tacrolimus were prepared using SFT to enhance its dissolution. The selected polymers included soluplus, PVP, HPMC, and porous chitosan. TPGS was used as a surfactant additive with chitosan, HPMC, and PVP. Soluplus dispersions were used to study the effect of processing parameters (time, temperature, and pressure) on loading efficiency (LE) and dissolution of the preparation. Physicochemical characterization was performed using DSC, X-ray diffraction, FTIR analysis, SEM, and in vitro drug release. Stability testing was evaluated after 3 months for selected dispersions. Significant improvement for the release profile was achieved for the prepared dispersions. Better release achieved in the soluplus dispersions which reached maximum cumulative release equal to 98.76% after 24 h. Drug precipitated in its amorphous form in all prepared dispersions except those prepared from chitosan. All dispersions were physically stable except for PVP preparations that contained TPGS which started to re-crystallize after one month. Prepared dispersions were proved to be affected by supercritical processing parameters. In conclusion, SFT was successfully used to prepare dispersions of tacrolimus that exhibited higher dissolution than raw drug. Dissolution rate and stability are affected by the type of the polymer.
他克莫司是一种生物利用度差且变化不定的免疫抑制剂。这可能与溶解度和溶出度有限有关。本研究的主要目的是使用超临界流体技术（SFT）制备他克莫司的固体分散体，以提高其溶出度。选择SFT是因为它比传统技术具有多种优势，如效率和稳定性。使用SFT制备了几种他克莫司的固体分散体以提高其溶出度。所选聚合物包括尤特奇（Soluplus）、聚乙烯吡咯烷酮（PVP）、羟丙甲纤维素（HPMC）和多孔壳聚糖。吐温80（TPGS）用作壳聚糖、HPMC和PVP的表面活性剂添加剂。使用尤特奇分散体研究加工参数（时间、温度和压力）对制剂载药量（LE）和溶出度的影响。使用差示扫描量热法（DSC）、X射线衍射、傅里叶变换红外光谱（FTIR）分析、扫描电子显微镜（SEM）和体外药物释放进行理化表征。对所选分散体在3个月后进行稳定性测试。所制备的分散体的释放曲线有显著改善。尤特奇分散体实现了更好的释放，在24小时后达到最大累积释放率等于98.76%。除了由壳聚糖制备的分散体之外，在所有制备的分散体中药物以无定形形式沉淀。除了含有TPGS的PVP制剂在一个月后开始重新结晶外，所有分散体在物理上都是稳定的。事实证明，所制备的分散体受超临界加工参数的影响。总之，成功使用SFT制备了他克莫司的分散体，其溶出度高于原料药。溶出速率和稳定性受聚合物类型的影响。
