Fabrication and Solid State Characterization of Ticagrelor Co-Crystals with Improved Solubility and Dissolution

Abstract

In the present study a new co-crystal of Ticagrelor with L-Tartaric acid has been prepared with improved solubility. Ticagrelor is a class VI drug with poor solubility and permeability; hence an attempt has been made to improve its solubility by co-crystallization technology.A co-crystal is a structurally homogeneous crystalline material containing an API and the co-former in definite stoichiometric amounts. In this study the conformer selected was L-Tartaric acid based on ease of hydrogen bond formation. The co-crystal of Ticagrelor with L-Tartaric acid was prepared in different ratios (1:1, 2:1, 1:2). Ticagrelor formed stable co-crystals in the ratios 1:1and2:1. The formation of co-crystal was confirmed by FTIR, DSC and PXRD. The dynamic solubility of co-crystals in the ratios 1:1 and 2:1 was increased by approximately 2.7 and 2.6 fold respectively as compared to pure drug. The in-vitrodissolution study demonstrated a 1.5 fold increase in the solubility for selected TIC:L-TAR (1:1) as compared to its TIC active pharmaceutical ingredient and TIC physical mixture.

Solubility Measurement and Mathematical Correlation of Ticagrelor in Different Pure Solvents

“…In this work, the onset temperature is used as the melting temperature ( T m ) of ticagrelor, and its value is 413.98 K, which is closer to the values (412.07 K) reported in ref . The small deviation was caused by the difference of the heating rate, and it was 10 K·min –1 , as reported in ref .…”

“…The improvement of the physicochemical properties of active pharmaceutical ingredients (APIs) with solubility-limited bioavailability is of paramount importance in the pharmaceutical development of drug molecules. , There are some studies reported that aimed to improve the solubility of active ingredient ticagrelor. A new cocrystal of ticagrelor with l -tartaric acid has been prepared by Shane and co-workers with improved solubility . Muhammad Inam and co-workers reported that two new cocrystals, ticagrelor with nicotinamide, have been prepared with improved solubility .…”

Solubility Measurement of Crystal Form II and Form V Ticagrelor in Several Pure Organic Solvents

“…In Chen’s work, the crystal form of raw material was pointed out same as that of a previous study, which showed the XRPD patterns and confirmed as Form II . However, the heating rate of DSC test was selected as 5 K/min rather than the standard 10 K/min given by the original patent, and the obtained melting point has a little deviation from Form II TCG .…”

“…In Chen's work, the crystal form of raw material was pointed out same as that of a previous study, which showed the XRPD patterns and confirmed as Form II. 38 However, the heating rate of DSC test was selected as 5 K/min rather than the standard 10 K/min given by the original patent, and the obtained melting point has a little deviation from Form II TCG. 6 Furthermore, according to the result of crystal stability study in this work, Form II TCG was unstable and would transform to Form V. Therefore, the static method was unacceptable in the solubility determination of Form II TCG and the reported solubility data were obviously different from that of this work.…”

Design and Characterization of Ticagrelor‐Loaded Chitosan Biopolymer to Improve Chemical and Biological Properties of the Drug

“…For instance, the TCG‐loaded self‐micro‐emulsifying drug delivery system exhibited higher permeability in Caco‐2 cells than the free TCG [2] . Furthermore, the co‐crystal of TCG with L‐Tartaric acid, [4] and solid dispersion of TCG in hydrophilic polymers [5,6] have been developed to improve the solubility and bioavailability of TCG. Moreover, combining povidone and TCG could enhance the dissolution rate of TCG [7] .…”