Designing of Stable Cocrystals of Cytarabine and Doxorubicin HCl Using Suitable Coformers

Abstract

In the present study cocrystal of cytarabine with L-tartaric acid and nicotinamide and
cocrystal of Doxorubicin HCl with maraviroc has been prepared. The cytarabine and doxorubicin HCl are
potential anticancer drugs used in the treatment of various types of cancer. Though they have certain advantages, they also have issues like low oral bioavailability, metabolic stability, toxicity and show major
side effects during the treatment. In order to enhance their therapeutic potential, an attempt has been
made to develop the cocrystals of both the drugs using crystal engineering. The prepared cocrystals will
exhibit enhanced improved oral bioavailability, metabolic stability, and therapeutic potential. A cocrystal
is a structurally homogenous crystalline material containing an API and the conformer in definite stochiometric amounts. In this study the coformers selected were L-tartaric acid and nicotinamide for cytarabine
and maraviroc for doxorubicin HCl based on the ease of hydrogen bond formation. The cocrystals of Cytarabine with L-Tartaric acid and doxorubicin HCl with maraviroc were prepared in ratio 1:1,1:2,2:1.
The cocrystals of Cytarabine with nicotinamide was prepared in ratio 1:1. Both the drugs formed stable
cocrystals with the selected coformers. The formation of cocrystal was confirmed by FTIR, DSC, and
PXRD. The saturation solubility of cytarabine with L-tartaric acid did not show higher solubility when
compared to pure cytarabine. The solubility of cytarabine with nicotinamide cocrystal 1:1 ratio was increased by 1.47 fold as compared to pure drug. And cocrystals of doxorubicin HCl-maraviroc showed
higher solubility when compared to pure doxorubicin HCl. The cocrystals of ratio 1:1, 1:2 and 2:1 showed
an increased solubility with an increase by 1.72, 1.68, and 2.46 folds, respectively as compared to pure
drug.