Rapid assessment of homogeneity and stability of amorphous solid dispersions by atomic force microscopy--from bench to batch.
Pharm Res
; 30(8): 2010-22, 2013 Aug.
Article
en En
| MEDLINE
| ID: mdl-23673553
ABSTRACT
PURPOSE:
To verify the robustness and fundamental value of Atomic Force Microscopy (AFM) and AFM-based assays to rapidly examine the molecular homogeneity and physical stability of amorphous solid dispersions on Hot-Melt-Extrudates.METHODS:
Amorphous solid dispersions were prepared with a Hot-Melt Extruder (HME) and profiled by Raman Microscopy and AFM following a sequential analytical routine (Multi-Scale-Imaging-of-Miscibiliy (MIMix)). Extrudates were analyzed before and after incubation at elevated temperature and humidity. The data were compared with published results as collected on miniaturized melt models. The value of molecular phase separation rates for long term stability prediction was assessed.RESULTS:
Data recorded on the extrudates are consistent with those published, and they can be compared side by side. Such direct data comparisons allow the identification of possible sources of extrudate heterogeneities. The surface roughness analysis of fracture-exposed interfaces is a novel quantitative way to trace on the nanometer scale the efficiencies of differently conducted HME-processes. Molecular phase separation rates are shown to be relevant for long term stability predictions.CONCLUSIONS:
The AFM-based assessment of APIexcipient combinations is a robust method to rapidly identify miscible and stable solid dispersions in a routine manner. It provides a novel analytical tool for the optimization of HME processes.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Preparaciones Farmacéuticas
/
Microscopía de Fuerza Atómica
/
Excipientes
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Pharm Res
Año:
2013
Tipo del documento:
Article
País de afiliación:
Suiza