Solid nanofoams based on cellulose nanofibers and indomethacin-the effect of processing parameters and drug content on material structure

TY - JOUR

T1 - Solid nanofoams based on cellulose nanofibers and indomethacin-the effect of processing parameters and drug content on material structure

AU - Bannow, J

AU - Benjamins, J-W

AU - Wohlert, J

AU - Löbmann, K

AU - Svagan, A J

N1 - Copyright © 2017 Elsevier B.V. All rights reserved.

PY - 2017/6/30

Y1 - 2017/6/30

N2 - The unique colloidal properties of cellulose nanofibers (CNF), makes CNF a very interesting new excipient in pharmaceutical formulations, as CNF in combination with some poorly-soluble drugs can create nanofoams with closed cells. Previous nanofoams, created with the model drug indomethacin, demonstrated a prolonged release compared to films, owing to the tortuous diffusion path that the drug needs to take around the intact air-bubbles. However, the nanofoam was only obtained at a relatively low drug content of 21wt% using fixed processing parameters. Herein, the effect of indomethacin content and processing parameters on the foaming properties was analysed. Results demonstrate that a certain amount of dissolved drug is needed to stabilize air-bubbles. At the same time, larger fractions of dissolved drug promote coarsening/collapse of the wet foam. The pendant drop/bubble profile tensiometry was used to verify the wet-foam stability at different pHs. The pH influenced the amount of solubilized drug and the processing-window was very narrow at high drug loadings. The results were compared to real foaming-experiments and solid state analysis of the final cellular solids. The parameters were assembled into a processing chart, highlighting the importance of the right combination of processing parameters (pH and time-point of pH adjustment) in order to successfully prepare cellular solid materials with up to 46 wt% drug loading.

AB - The unique colloidal properties of cellulose nanofibers (CNF), makes CNF a very interesting new excipient in pharmaceutical formulations, as CNF in combination with some poorly-soluble drugs can create nanofoams with closed cells. Previous nanofoams, created with the model drug indomethacin, demonstrated a prolonged release compared to films, owing to the tortuous diffusion path that the drug needs to take around the intact air-bubbles. However, the nanofoam was only obtained at a relatively low drug content of 21wt% using fixed processing parameters. Herein, the effect of indomethacin content and processing parameters on the foaming properties was analysed. Results demonstrate that a certain amount of dissolved drug is needed to stabilize air-bubbles. At the same time, larger fractions of dissolved drug promote coarsening/collapse of the wet foam. The pendant drop/bubble profile tensiometry was used to verify the wet-foam stability at different pHs. The pH influenced the amount of solubilized drug and the processing-window was very narrow at high drug loadings. The results were compared to real foaming-experiments and solid state analysis of the final cellular solids. The parameters were assembled into a processing chart, highlighting the importance of the right combination of processing parameters (pH and time-point of pH adjustment) in order to successfully prepare cellular solid materials with up to 46 wt% drug loading.

KW - Journal Article

U2 - 10.1016/j.ijpharm.2017.04.041

DO - 10.1016/j.ijpharm.2017.04.041

M3 - Journal article

C2 - 28434935

SN - 0378-5173

VL - 526

SP - 291

EP - 299

JO - International Journal of Pharmaceutics

JF - International Journal of Pharmaceutics

IS - 1-2

ER -