How rotational speed of planetary ball mill and polymer load influence the performance and water vapor sorption in solid dispersions composed of tadalafil and soluplus  

作　　者：Karol Kubat Anna Krupa Witold Brniak Agnieszka Węgrzyn Dorota Majda Agata Bogdał Hubert Harańczyk 

机构地区：[1]Department of Medical Physics,Faculty of Physics,Institute of Physics,Jagiellonian University,Cracow,Poland [2]Department of Pharmaceutical Technology and Biopharmaceutics,Faculty of Pharmacy,Collegium Medicum,Jagiellonian University,Cracow,Poland [3]Faculty of Chemistry,Jagiellonian University,Cracow,Poland

出　　处：《Particuology》2023年第2期37-46,共10页颗粒学报（英文版）

基　　金：Sonata Bis (grant no.DEC-2019/34/E/NZ7/00245)financed by the National Science Centre in Poland;support (grant no.7150/E-338/M/2017)financed by the Polish Ministry of Science and Higher Education;the equipment purchased thanks to the financial support of the European Regional Development Fund in the framework of the Polish Innovation Economy Operational Program (contract no.POIG.02.01.00-12-023/08).

摘　　要：The presence of residual water may deteriorate the performance of amorphous solid dispersions prepared by ball milling,affecting molecular mobility,crystallinity,particle size and finally,the drug dissolution rate.As the stability of these metastable systems depend on both formulation and process variables,the aim of this study was to assess for the first time,the impact that the polymer load and the rotational speed applied upon high energy ball milling could have on the performance of binary co-milled solid dispersions composed of tadalafil(a hydrophobic crystalline drug)and Soluplus(an amphiphilic,hygroscopic amorphous polymer).Each of these variables was tested at three levels.Scanning electron microscopy,laser diffraction and X-ray powder diffraction were used to analyze morphology,particle size distribution and crystallinity of ball milled formulations respectively.Dissolution studies were also carried out.Advanced tools of applied physics,namely solid state 1H NMR and relaxometry were used to assess the structure and water mobility upon gaseous phase hydration on storage.It was shown that both tested variables determined the particle size of the formulation.When the rotational speed of 400 rpm was used,all solid dispersion were XRD-amorphous,but to ensure the immediate release of tadalafil its micellar solubilization in Soluplus was necessary.While the formulation was exposed to water vapor,the hydration level increased with an increasing polymer load as well.Hence,the rotational speed governed the space available for the adsorption of water molecules and their organization in a monolayer or multilayers.Such behavior may have impact on the kinetics of the amorphous drug recrystallization,and finally deteriorate its dissolution.

关 键 词：TADALAFIL Soluplus Solid dispersion Relaxation time MILLING NMR 

分 类 号：TG1[金属学及工艺—金属学]