1 research outputs found
Does Media Choice Matter When Evaluating the Performance of Hydroxypropyl Methylcellulose Acetate Succinate-Based Amorphous Solid Dispersions?
Hydroxypropyl methylcellulose acetate
succinate (HPMCAS)
is a weakly
acidic polymer that is widely used in the formulation of amorphous
solid dispersions (ASDs). While the pH-dependent solubility of HPMCAS
is widely recognized, the role of other solution properties, including
buffer capacity, is less well understood in the context of ASD dissolution.
The goal of this study was to elucidate the rate-limiting steps for
drug and HPMCAS release from ASDs formulated with two poorly water
soluble model drugs, indomethacin and indomethacin methyl ester. The
surface area normalized release rate of the drug and/or polymer in
a variety of media was determined. The HPMCAS gel layer apparent pH
was determined by incorporating pH sensitive dyes into the polymer
matrix. Water uptake extent and rate into the ASDs were measured gravimetrically.
For neat HPMCAS, the rate-limiting step for polymer dissolution was
observed to be the polymer solubility at the polymer–solution
interface. This, in turn, was impacted by the gel layer pH which was
found to be substantially lower than the bulk solution pH, varying
with medium buffer capacity. For the ASDs, the HPMCAS release rate
was found to control the drug release rate. However, both drugs reduced
the polymer release rate with indomethacin methyl ester having a larger
impact. In low buffer capacity media, the presence of the drug had
less impact on release rates when compared to observations in higher
strength buffers, suggesting changes in the rate-limiting steps for
HPMCAS dissolution. The observations made in this study can contribute
to the fundamental understanding of acidic polymer dissolution in
the presence and absence of a molecularly dispersed lipophilic drug
and will help aid in the design of more in vivo relevant
release testing experiments