Comparative studies on physicochemical stability of cyclosporine A-loaded amorphous solid dispersions

H Sato, Y Kawabata, K Yuminoki, N Hashimoto… - International journal of …, 2012 - Elsevier
H Sato, Y Kawabata, K Yuminoki, N Hashimoto, Y Yamauchi, K Ogawa, T Mizumoto…
International journal of pharmaceutics, 2012Elsevier
The present study aimed to evaluate the physical stability on amorphous solid dispersion
(SD) of cyclosporine A (CsA) employing hydroxypropyl cellulose (HPC). SD formulations (5–
30% CsA) of CsA such wet-milled SD (WM/SD) and freeze-dried SD (FD/SD) were prepared,
and both SD formulations were stored at 40° C/75% relative humidity for 8 weeks.
Transitions in morphology, dissolution behavior, crystallinity and thermal behavior of CsA
were evaluated. There was at least 84-fold improvement in initial dissolution rate of SD …
The present study aimed to evaluate the physical stability on amorphous solid dispersion (SD) of cyclosporine A (CsA) employing hydroxypropyl cellulose (HPC). SD formulations (5–30% CsA) of CsA such wet-milled SD (WM/SD) and freeze-dried SD (FD/SD) were prepared, and both SD formulations were stored at 40°C/75% relative humidity for 8 weeks. Transitions in morphology, dissolution behavior, crystallinity and thermal behavior of CsA were evaluated. There was at least 84-fold improvement in initial dissolution rate of SD formulations compared with that of amorphous CsA powder, although their dissolution rate was gradually decreased under accelerated conditions. In particular, aged FD/SD with a drug load of 30% exhibited highly limited dissolution as evidenced by 40% reduction of solubility after 8 weeks of storage. In contrast, aged WM/SD exhibited less reduction in dissolution rate compared with FD/SD. No significant changes were seen in crystallinity and thermal behavior after aging of SD formulations for 8 weeks; however, electron microscopic observations revealed aggregation of drug molecules/particles in the aged FD/SD, possibly leading to the reduced dissolution. From these findings, stability on CsA-loaded SD might be variable depending on the preparation methodology, and the wet-milling approach could be a viable option for preparing efficacious SD formulations with improved stability.
Elsevier
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