Amorphous solid dispersions are a promising way to improve the dissolution rate and bioavailability of hydrophobic drugs. However, they have a tendency to crystallise to the stable crystalline form during processing or storage, leading to changed physicochemical properties. The study of the stability for amorphous solid dispersions is important. Here, the thermodynamic stability of griseofulvin and indomethacin in polymers were studied using differential scanning calorimetry (DSC), and the effect of moisture on the kinetic stability of indomethacin or griseofulvin solid dispersions with PVP was studied using dynamic vapour sorption – near infrared (DVS - NIR). DSC could estimate the solubility of griseofulvin in HPMCAS accurately but not for the other models. DVS-NIR showed that the water uptake by the solid dispersions of indomethacin and PVP was lower than the values predicted from the sum of the water isotherm for individual components. The reason for this reduction was due to the hydrogen bonds formed between IMC and PVP occupied the water binding sites on PVP. The moisture sorption reduction in the amorphous solid dispersions can stabilise the solid dispersions. A reduced water uptake was also observed for the solid dispersion of 70% GSF and PVP compared to the predicted value. As no hydrogen bonds formed between GSF and PVP, the reason for this reduction was that the water binding sites on PVP were sterically hindered by GSF through the formation of the solid dispersion. A weight loss was absent in the DVS curve for the solid dispersion while crystallisation happened. This was due to the expelled water from amorphous GSF was sorbed by PVP. DVS-NIR offers a great promise in understanding the mechanism of stabilisation of solid dispersions, and therefore may be useful to predict the stability of new API dispersions.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:639715 |
| Date | January 2015 |
| Creators | Li, W. |
| Publisher | University College London (University of London) |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://discovery.ucl.ac.uk/1462444/ |
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