Terahertz and Raman Spectroscopic Investigation of Monohydrate Cocrystal of Antitubercular Isoniazid with Protocatechuic Acid.

Yanhua Bo,Zhi Hong,Yong Du,Jiyuan Fang,Jianjun Liu,Ziming Zhang,Jiadan Xue

doi:10.3390/pharmaceutics13081303

Yanhua Bo, Zhi Hong + Show 5 more

Open Access

https://doi.org/10.3390/pharmaceutics13081303

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Abstract

Pharmaceutical cocrystal provides an alternative modification strategy for the formulation development of drugs owning to their potential ability to improve the physicochemical properties of active pharmaceutical ingredients (APIs) efficiently by changing inter-molecular interactions between raw materials. Isoniazid (INH) is an indispensable main drug for the treatment of tuberculosis, but its tablet formulation is unstable and prone to degradation. In the present study, the monohydrate cocrystal of INH and protocatechuic acid (PA) was prepared by solvent evaporation using PA as cocrystal former to optimize the properties of INH. The parent materials and corresponding 1:1 molar ratio INH-PA monohydrate cocrystal have been characterized by the terahertz time-domain (THz-TDS) and Raman spectroscopy. The THz absorption spectra displayed that there were obvious differences between the peaks of experimental cocrystal and the parent materials, and the same situation was found in Raman vibrational spectra. In addition, density functional theory (DFT) was applied to simulating and optimizing the structure of INH-PA monohydrate cocrystal and supplied corresponding vibrational modes. Our results provided a unique method to characterize the formation of INH-PA monohydrate cocrystal at the molecular-level and a lot of information about cocrystal structure and intra-molecular and/or inter-molecular hydrogen bond interactions in the emerging pharmaceutical cocrystal fields.

Highlights

Tuberculosis (TB) is a global emergency case announced by the World Health Organization (WHO) and among the top 10 causes of death [1,2]
The vibrational spectra of solid-state INH, protocatechuic acid (PA), physical mixtures and INH-PA monohydrate cocrystal were obtained by THz and Raman spectra
It can be perceived that there are some differences between the vibrational spectra of INH-PA monohydrate cocrystal and those of original materials

Summary

Introduction

Tuberculosis (TB) is a global emergency case announced by the World Health Organization (WHO) and among the top 10 causes of death [1,2]. Isoniazid (INH, as shown in Figure 1), the principal component in the so-called ‘triple therapy’ and different FDCs [5], tends to degrade in the FDCs involving INH and rifampicin (RIF). Oxidative stress will occur in the patients treated with anti-TB drugs such as INH and RIF, which tend to cause hepatotoxicity [6]. In order to improve its pharmaceutical performance and enhance the stability of tablet formulations, it is urgent to explore new solid forms [7]. Cocrystal is generally defined as the crystalline single-phase materials [8] formed by two or more solid-state neutral compounds in a certain stoichiometric ratio under the influence of inter-molecular interactions [9]. Cocrystallization provides different avenues, where any pharmaceutical substance may form cocrystals without having ionizable groups [10]

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