Study on redispersibility of drug nanocrystals particles during storage: Novel understanding based on water adsorption and glass transition of amorphous matrix formers.

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The objective of this study was to understand the influence of the water adsorption and glass transition of matrix formers on redispersibility in water of drug nanocrystals-aggregated particles(NAP) during storage, and the critical storage strategy for NAP powders were determined based on the Guggenheim-Anderson-de Boer (GAB) and the Gordon-Taylor models. Apigenin was used as model drug. Six kinds of matrix formers sucrose(SU), lactose(LA), trehalose(TR), inulin(IN), maltodextrin(MA) and PVPK30(PV) were used to prepare apigenin nanocrystals-aggregated particles (AN-NAPs). The results demonstrated that the adsorption isotherms curves of six kinds of matrix formers based AN-NAPs all showed typical II (S) type adsorption. The water activity significantly influenced the redispersibility of AN-NAP, which could be attributed to the microstructure collapse of amorphous matrix induced by moisture adsorption at high water activity or high moisture. MD based AN-NAP(AN-NAP/MD) exhibited much better redispersibility at high water activity(0.689) compared with the other amorphous matrix formers. MD was able to significantly enlarge the Tg of AN-NAP system and prevent from aggregation of AN-NAP compared to other matrix formers. And the critical water activity and moisture content of AN-NAPs were in the ranges of 0.015-0.545 and 0.0412-0.1508g water/g dry matter, respectively. Of all amorphous matrix based NAPs, the critical water activity of AN-NAP/MD was the highest (0.545), and the critical moisture content was 0.1003g water/g dry matter, and followed by TR based on AN-NAP. MD could be used as an excellent matrix former for nanocrystals-aggregated particles during storage. Therefore, the roles of water adsorption and glass transition of matrix formers on redispersibility of drug nanocrystals-aggregated particles during storage was successful elucidated, and the critical storage strategy was proposed based on the GAB model and the Gordon-Taylor model.