COCRYSTAL OF ATORVASTATIN CALCIUM – MALONIC ACID

Abstract

Cocrystal is a relatively new solid form of active
pharmaceutical ingredient that offers an alternative
platform in improving physicochemical properties of
active pharmaceutical ingredients Padrela et al.,
2009; Mashhadi et al., 2004. Cocrystal is defined as
a stoichiometric multi-component system connected
by non-covalent interactions where all the
components neutral and solid under ambient
conditions Thakuria et al., 2013. Cocrystal can be
constructed through interaction hydrogen bonding,
pi-stacking, and van der Waals forces  Mashhadi et
al., 2004. A pharmaceutical cocrystal is composed of
an API and an appropriate coformer as carboxylic
acids and amides Qiao et al., 2011.
Cocrystallization of active pharmaceutical ingredient
is an opportunity for enhancement of important
physiochemical properties of an active
pharmaceutical ingredient without changing its
molecular structure Maeno et al., 2014.
Atorvastatin Calcium (AC), ([(R-(R*,R*)]-2-(4-
fluorophenyl)-beta, delta-dihydroxy-5-(1-
methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-
1H-pyrrole-1-heptanoic acid), calcium salt (2:1)
trihydrate ([C33H34FN2O5]2Ca.3H2O), is considered as
one of the most effective of synthetic lipid lowering
agent Shete et al., 2010. The drug is orally used to
reduce of total cholesterol, low density lipoprotein
and triglycerides Anwar et al., 2011. There are 42
crystalline structures of AC Shayanfar et al., 2013.
However, chance to create AC into another crystal
structure to improving physicochemical properties of
AC is still fully open Chadha et al., 2012.
In the present study, we explored cocrystallization of
AC by solvent evaporation method. This study aimed
to confirm whether AC was able to form cocrystal
with malonic acid (MA) as coformer. AC-MA
cocrystal was prepared by solvent evaporation
method by using methanol as solvent.
Characterization of cocrystal was done by powder Xray
diffractometry (PXRD), differential scanning
calorimetry (DSC), fourier transform infrared (FTIR)
spectroscopy and scanning electron microscopy
(SEM).