Dynamics and stabilization mechanisms of amorphous solid dispersions
2016
A growing problem in the pharmaceutical industry is the poor water-solubility of new
candidate drugs22, 41. It is estimated that 75% of drugs under development are considered
to have poor water-solubility19, and a low solubility heavily diminishes the
chance of drug uptake and therapeutic effect. A method that has recieved attention
lately to achieve increased solubility is to make use of a formulation strategy known
as an amorphous solid dispersion (ASD)13, 31. The amorphous state of the pharmaceutical
eliminates the impact of lattice energy resulting in increased solubility.
However, since the pharmaceutical is in its thermodynamically metastable amorphous
state, the dispersion may crystallize over relevant pharmaceutical timescales
thus cancelling the solubility advantage. Stabilizing amorphous pharmaceuticals
with polymers in ASDs have proven possible in previous studies5, 42, 63, 59, although
the stabilization has been attributed to different mechanisms.
In this work, the relationship between anti-plasticization effects and hydrogen bonding
was investigated in ASDs with ibuprofen and felodipine using dielectric spectroscopy,
differential scanning calorimetry and FTIR spectroscopy. The physical
stability of ibuprofen was drastically improved, stabilizing the drug in its amorphous
state over a timescale of months. It was found that the polymeric glass transition
temperature of the polymer did not correlate with the stabilization effect of ibuprofen.
The effect was instead attributed to hydrogen bonding between polymer and
ibuprofen. Dispersions using felodipine were however not succesfully prepared.
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