An investigation into the factors governing the degree of dissolution enhancement of solid dispersion for poorly soluble drugs

Abstract

Solid dispersion (SD) formulation has attracted much
attention due to its potential in enhancing dissolution
performances of poorly soluble active pharmaceutical ingredients
(API). Recently, a review on dissolution performances of SDs
classifies the improvement into 3 categories, where 82 % of the
studies showed improved bioavailability, 8 % showed reduced
bioavailability and 10 % revealed similar bioavailability as
compared to pure APIs. This indicates the inconsistent degrees of
dissolution improvement of poorly soluble APIs in SD. Although
a few factors related to the choice of carriers have been suggested
to contribute to the dissolution improvement, however, the
underlying factor determining the discrepancy in the degree of
dissolution improvement remains in vague. It is hypothesized
that the API contributes to the degree of dissolution
improvement of SD. Hence, the factor of amorphous solubility
advantage of API which leads to the different degrees of
dissolution enhancement of SD is investigated in this research.
Polyvinylpyrrolidone vinyl acetate (PVPVA)-based SD is
prepared with three poorly soluble APIs. Physicochemical
properties of SD were characterized using infrared spectroscopy,
differential scanning calorimetry (DSC) and X-ray powder
diffraction. The dissolution efficiency of each SD was calculated
and compared to physical mixture and pure API. Theoretical
amorphous solubility advantage for each API was calculated
using the thermal properties obtained from DSC. The calculated
values were found to be correlating well with the dissolution
enhancement of the respective SDs. Hence, this theoretical
approach can be utilized as an initial screening tool of API
candidates in SD formulation during early pharmaceutical
development.