Mechanochemical Synthesis and Physicochemical Characterization of Isoniazid and Pyrazinamide Co-crystals With Glutaric Acid

Abstract

The present work reports two novel pharmaceutical co-crystals; 2:1 isoniazid-glutaric acid (INHGA) and 2:1 pyrazinamide-glutaric acid (PGA). Isoniazid and pyrazinamide are key first-line drugs used for the treatment of tuberculosis. The co-crystals were produced via solid-state and solvent assisted grinding methods. Thermal characteristics of the samples were obtained using the differential scanning calorimetry, hot stage microscopy, and thermogravimetric analyses. The morphology of the powder samples by scanning electron microscopy, structural analysis by Fourier transform infrared spectroscopy and powder X-rays diffraction ensured co-crystal formation. Thermal analyses confirmed the co-crystals with new melting transitions ranging between their respective starting materials. Unique morphologies of the co-crystal particles were clear in SEM micrographs. The formation of intermolecular interactions with the co-crystal former was confirmed by the FT-IR spectral band shifting and was supported by distinct PXRD patterns of co-crystals thereby authenticating the successful co-crystal formation. In vitro solubility evaluation of the synthesized co-crystals by HPLC suggested a remarkable increase in solubility of both INH and PZA in their respective co-crystals.

Multistage Extraction of Star Anise and Black Pepper Derivatives for Antibacterial, Antioxidant, and Anticancer Activity

“…The peaks at 1,263 and 1,101 cm −1 were attributed to C-O-C stretching vibrations, indicating the existence of aromatic ether (Jia et al, 2020). The stretching vibration of C=O is 1,686 cm −1 (Ngilirabanga et al, 2020). All these characteristic peaks proved that p-methoxybenzoic acid (anisic acid) was obtained.…”

Biopolymer-Capped Pyrazinamide-Loaded Colloidosomes: In Vitro Characterization and Bioavailability Studies

“…PZA showed characteristic absorptions at 3409 cm –1 due to N–H stretching, 3288 cm –1 ( sym N–H), 3145 cm –1 due to stretch of the C–H band and carboxylic O–H group, 3150 cm –1 (C–H stretch), and 1705 cm –1 due to the carbonyl stretch (C=O). − Alginate shows an absorption band at 1604.64, 1417.68 cm –1 due to symmetrical vibrations of the COO – group, 1305.80 cm –1 due to v C–O str, and 1037.70 cm –1 in the saccharide region due to guluronic units of the v CO–C group. Also, the saccharide region aids in the formation of spherical structures .…”

A Micro-Configured Multiparticulate Reconstitutable Suspension Powder of Fixed Dose Rifampicin and Pyrazinamide: Optimal Fabrication and In Vitro Quality Evaluation

“…Generally, the excipients showed relatively high single decomposition temperatures of 300 °C and above representing their own distinct stability and purity [ 78 , 79 ]. Pyrazinamide’s thermal breakdown was initiated at 125 °C and reached a point of complete thermal decay at 200 °C Figure 3 I [ 80 ] while rifampicin showed more resistance to heat deformation with a thermal event starting at 240 °C and terminal weight loss continuing even at over 800 °C ( Figure 3 J) [ 74 ]. Thermal decomposition of the placebo and drug loaded formulation began at 200 °C and 125 °C, respectively with complete decay noted at ≥800 °C for placebo and ≥400 °C for the drug containing delivery system ( Figure 3 K,L).…”

“…The pure drug pyrazinamide ( Figure 4 I) displayed specific peaks of N-H stretches at vibrations of 3414 cm −1 and 3154 cm −1 , C=O stretches at 1698 cm −1 , C=N bends at 1596 cm −1 , C=C bends at 1374 cm −1 and C-N ring bends at 1166 cm −1 [ 34 , 80 , 92 ]. The pure drug rifampicin documented peaks at 3496 cm −1 representing N-H stretch, O-H stretches at 2984 cm −1 , C=O (keto group) stretches at 1694 cm −1 , C=O (amine group) at 1794 cm −1 and C=C ring stretches at 1456 cm −1 in Figure 4 J [ 93 , 94 , 95 ].…”