Cirri Marzia, Mura Paola, Valleri Maurizio, Brunetti Letizia
Department of Chemistry, University of Florence, via Schiff 6, Sesto Fiorentino, 50019 Florence, Italy.
Menarini Manufacturing Logistics and Services, s.r.l. (AMMLS), 50019 Florence, Italy.
Pharmaceutics. 2020 Jun 1;12(6):503. doi: 10.3390/pharmaceutics12060503.
The aim of this work was to evaluate the effectiveness of mesoporous clays or silicas to develop fast-dissolving glyburide tablets based on a liquisolid approach. Selected clay (NeusilinUS2) and silica (Aeroperl300) allowed preparation of innovative drug liquisolid systems containing dimethylacetamide or 2-pyrrolidone as drug solvents, without using coating materials which are necessary in conventional systems. The obtained liquisolid powders were characterized for solid-state properties, flowability, compressibility, morphology, granulometry, and then used for directly compressed tablet preparation. The developed liquisolid tablets provided a marked drug dissolution increase, reaching 98% dissolved drug after 60 min, compared to 40% and 50% obtained from a reference tablet containing the plain drug, and a commercial tablet. The improved glyburide dissolution was attributed to its increased wetting properties and surface area, due to its amorphization/solubilization within the liquisolid matrix, as confirmed by DSC and PXRD studies. Mesoporous clay and silica, owing to their excellent adsorbent, flow, and compressibility properties, avoided use of coating materials and considerably improved liquid-loading capacity, reducing the carrier amount necessary to obtain freely flowing powders. NeusilinUS2 showed a superior performance than Aeroperl300 in terms of the tablet's technological properties. Finally, simplicity and cost-effectiveness of the proposed approach make it particularly advantageous for industrial scale-up.
本研究的目的是评估介孔粘土或二氧化硅基于液固法开发速溶格列本脲片的有效性。选用的粘土(NeusilinUS2)和二氧化硅(Aeroperl300)能够制备创新的药物液固系统,该系统以二甲基乙酰胺或2-吡咯烷酮作为药物溶剂,无需使用传统系统中必需的包衣材料。对所得的液固粉末进行固态性质、流动性、可压缩性、形态、粒度分析等表征,然后用于直接压片制备。所开发的液固片显著提高了药物溶出度,60分钟后药物溶出率达到98%,相比之下,含普通药物的参比片和市售片的溶出率分别为40%和50%。格列本脲溶出度的提高归因于其在液固基质中发生非晶化/增溶作用后润湿性和表面积的增加,DSC和PXRD研究证实了这一点。介孔粘土和二氧化硅由于其优异的吸附、流动和可压缩性能,无需使用包衣材料,并显著提高了液体负载能力,减少了获得自由流动粉末所需的载体用量。就片剂的工艺性能而言,NeusilinUS2表现出比Aeroperl300更优异的性能。最后,所提出方法的简单性和成本效益使其在工业放大生产中特别具有优势。