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--颗粒学报PARTICUOLOGY

Kubat, K., Krupa, A., Brniak, W., Węgrzyn, A., Majda, D., Bogdał, A., & Harańczyk, H. (2023). 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. Particuology, 73, 37-46. https://doi.org/10.1016/j.partic.2022.04.003

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

Karol Kubat ^a *, Anna Krupa ^b^*, Witold Brniak^b, Agnieszka Węgrzyn ^c, Dorota Majda ^c, Agata Bogdał^a, Hubert Harańczyk ^a

a Department of Medical Physics, Faculty of Physics, Institute of Physics, Jagiellonian University, Cracow, Poland
b Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Pharmacy, Collegium Medicum, Jagiellonian University, Cracow, Poland
c Faculty of Chemistry, Jagiellonian University, Cracow, Poland

10.1016/j.partic.2022.04.003

Volume 73, February 2023, Pages 37-46

Received 18 January 2022, Revised 5 April 2022, Accepted 13 April 2022, Available online 4 May 2022, Version of Record 17 May 2022.

E-mail: karol.kubat@doctoral.uj.edu.pl; a.krupa@uj.edu.pl

Highlights

• Immediate release of tadalafil due to amorphization and solubilization in Soluplus.

• Soluplus loading controls hydration of solid dispersions on storage.

• Rotational speed determines the space available for adsorption of water molecules.

Abstract

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.

Graphical abstract

Keywords

Tadalafil; Soluplus; Solid dispersion; Relaxation time; Milling; NMR

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