Preparation and physicochemical characterization of a solid dispersion of (3, 5, 6-trimethylpyrazin-2-yl) methyl 3-methoxy-4-[(3, 5, 6-trimethylpyrazin-2-yl) methoxy] benzoate (VA-T) and polyvinylpyrrolidone

• Published in: Chinese journal of natural medicines Vol. 13; no. 11; pp. 861 - 866
• Main Authors: CAO, Sa-Li, HOU, Peng, LI, Bin, FU, Jing, YIN, Xing-Bin, DANG, Xiao-Fang, YANG, Chun-Jing, ZHANG, Jin, ZHANG, Hui, LEI, Hai-Min, NI, Jian
• Format: Journal Article
• Language: English
• Published: China Elsevier B.V 01.11.2015
• Subjects: Benzoates - administration & dosage; Benzoates - chemistry; Brain Ischemia - drug therapy; Chemistry, Pharmaceutical - methods; Dissolution; Drug Delivery Systems; Ischemic stroke; Physicochemical characterization; Povidone - chemistry; Solid dispersions; Solubility; VA-T; Physicochemical characterization; Solid dispersions; VA-T; Ischemic stroke; Dissolution
• ISSN: 1875-5364; 1875-5364
• DOI: 10.1016/S1875-5364(15)30090-X

Ischemic brain injury is a major disease which threatens human health and safety. (3, 5, 6-trimethylpyrazin-2-yl) methyl 3-methoxy-4-[(3, 5, 6-trimethylpyrazin-2-yl) methoxy] benzoate (VA-T), a newly discovered lead compound, is effective for the treatment of ischemic brain injury and its sequelae. But the poor solubility of VA-T leads to poor dissolution and limited clinical application. In order to improve the dissolution of VA-T, the pharmaceutical technology of solid dispersions was used in the present study. VA-T/polyvinylpyrrolidone (PVP) solid dispersion was prepared by the solvent method. The dissolution studies were carried out and solid state characterization was evaluated by differential scanning calorimetry (DSC), infrared spectroscopy (IR), x-ray diffraction (XRD) and scanning electron microscopy (SEM). The dissolution rate of VA-T was significantly improved by solid dispersion compared to that of the pure drug and physical mixture. The results of DSC and XRD indicated that the VA-T solid dispersion was amorphous. The IR spectra showed the possible interaction between VA-T and PVP was the formulation of hydrogen bonding. The SEM analysis demonstrated that there was no VA-T crystal observed in the solid dispersions. The ideal drug-to-PVP ratio was 1:5. In conclusion, the solid dispersion technique can be successfully used for the improvement of the dissolution profile of VA-T.