One way to increase the slow dissolution rate and the
associated
low bioavailability of newly developed active pharmaceutical ingredients
(APIs) is to dissolve the API in a polymer, leading to a so-called
amorphous solid dispersion (ASD). However, APIs are often supersaturated
in ASDs and thus tend to crystallize during storage. The kinetics
of the crystallization process is determined by the amount of water
the ASD absorbs during storage at relative humidity (RH), storage
temperature, polymer type, and the drug load of the ASD. Here, the
crystallization kinetics and shelf life of spray-dried ASDs were investigated
for ASDs consisting of nifedipine (NIF) or celecoxib (CCX) as the
APIs and of poly(vinylpyrrolidone-co-vinyl acetate)
or hydroxypropyl methylcellulose acetate succinate as polymers. Samples
were stored over 2 years at different RHs covering conditions above
and below the glass transition of the wet ASDs. Crystallization kinetics
and onset time of the crystallization were qualitatively studied by
using powder X-ray diffraction and microscopic inspection and were
quantitatively determined by using differential scanning calorimetry.
It was found that the NIF ASDs crystallize much faster than CCX ASDs
at the same drug load and at the same storage conditions due to both
higher supersaturation and higher molecular mobility in the NIF ASDs.
Experimental data on crystallization kinetics were correlated using
the Johnson–Mehl–Avrami–Kolmogorov equation.
A detailed thermodynamic and kinetic modeling will be performed in
Part 2 of this paper series.