Adeleke Oluwatoyin A, Choonara Yahya E, du Toit Lisa C, Kumar Pradeep, Pillay Viness
Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutics, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown, 2193, Johannesburg, South Africa.
Pharm Res. 2015 Jul;32(7):2384-409. doi: 10.1007/s11095-015-1631-4. Epub 2015 Jan 29.
To elucidate the mechanisms of construction and performance of a porosity controlled, multi-elemental transbuccal system employing experimental and computational approaches.
The production of the formulation was guided through a Box-Benkhen design employing homogenization coupled with lyophilization. The physicochemical and physicomechanical properties of the experimental design formulations were quantified with relevant analytical techniques. The influence of changes in porosity measures on the magnitude of these physical properties were explored mathematically. Furthermore, experimental outputs from the Box-Behnken design formulations were fitted into set limits and optimized using the response surface method. The optimized porosity-controlled formulation was subjected to mechanistic experimental and computational elucidations.
In general, the changes in magnitudes of studied porosity quantities had significant impact on formulation physicochemical and physicomechanical properties. The generation of an optimized formulation validated the stability and accuracy of the Box-Behnken experimental design. Experimental investigations revealed that the construction of this formulation is as a result of non-destructive physical interactions amongst its make-up compounds while its mechanism of performance is anchored mainly upon a gradual collapse of its ordered porous structure. Furthermore, the molecule mechanics simulations quantitatively predicted the molecular interactions inherent to multicomponent matrix formation and the mucoadhesion mechanism.
The fabrication and performance mechanisms of the porosity-controlled transbuccal system was successfully explored.
采用实验和计算方法阐明孔隙率可控的多元素经颊给药系统的构建机制和性能。
通过采用均质化结合冻干的Box - Benkhen设计来指导制剂的制备。用相关分析技术对实验设计制剂的物理化学和物理机械性质进行量化。从数学上探讨孔隙率测量值的变化对这些物理性质大小的影响。此外，将Box - Behnken设计制剂的实验输出拟合到设定限度内，并使用响应面法进行优化。对优化后的孔隙率可控制剂进行机理实验和计算阐释。
总体而言，所研究的孔隙率量的变化对制剂的物理化学和物理机械性质有显著影响。优化制剂的生成验证了Box - Behnken实验设计的稳定性和准确性。实验研究表明，该制剂的构建是其组成化合物之间非破坏性物理相互作用的结果，而其性能机制主要基于其有序多孔结构的逐渐坍塌。此外，分子力学模拟定量预测了多组分基质形成中固有的分子相互作用和粘膜粘附机制。
成功探索了孔隙率可控经颊给药系统的制备和性能机制。
