1 research outputs found
An Experimental and Theoretical Investigation of Loperamide Hydrochloride–Glutaric Acid Cocrystals
Cocrystallization
is a powerful method to improve the physicochemical properties of
drugs. Loperamide hydrochloride is a topical analgesic
for the gastrointestinal tract showing low and pH-dependent solubility;
for this reason, an enhancement of its solubility or dissolution rate,
particularly at the pH of the intestinal tract, could improve its
local efficacy. Here we prepared cocrystals of this active principle
with glutaric acid and so obtained a new
crystalline solid representing a viable alternative to improve the
physicochemical
properties and thus the pharmaceutical behavior of the drug. Differential
scanning calorimetry, X-ray powder diffraction, Fourier infrared spectroscopy,
solid-state NMR, and scanning electron microscopy coupled to the energy-dispersive
X-ray spectrometry were used to investigate the new solid-phase formation.
DFT calculations at B3LYP/6-31GÂ(d) level of theory, in the gas phase,
including frequencies computation, provided a rationale for the interaction
between loperamide hydrochloride and glutaric acid. The cocrystals
showed improved water solubility in comparison with loperamide HCl,
and the pharmaceutical formulation proposed was able to release the
drug more rapidly in comparison with three reference commercial products
when tested at neutral pH values