On the plasticizing properties of divalproex sodium: physicochemical and spectroscopic characterization studies

• Published in: Pharmaceutical development and technology Vol. 24; no. 4; pp. 455 - 464
• Main Authors: Khatri, Pinak, Desai, Dipen, Minko, Tamara
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 21.04.2019
• Subjects: Calorimetry, Differential Scanning - methods; Chemical Phenomena; Chemistry, Pharmaceutical - methods; glass transition temperature; Nontraditional plasticizer; plasticization; Plasticizers - analysis; Plasticizers - chemistry; Rheology - methods; Spectroscopy, Fourier Transform Infrared - methods; Spectrum Analysis, Raman - methods; Valproic Acid - analysis; Valproic Acid - chemistry; glass transition temperature; plasticization; Nontraditional plasticizer
• ISSN: 1083-7450; 1097-9867
• DOI: 10.1080/10837450.2018.1514049

The objective of the research was to demonstrate the plasticization properties of divalproex sodium, due to its component-valproic acid, on ethyl cellulose, which could prove beneficial for film fabrications or hot melt extrusion based formulations. Films containing 10-50% w/w (DVS/EC) as dry weight were prepared using solvent evaporation method and characterized using texture analyzer, hybrid rheometer, differential scanning calorimetry, thermogravimetry, X-ray diffractometry, polarized microscopy, FTIR, and Raman spectroscopy. It was found that there was a decrease in average peak load, melt viscosity, and glass transition temperature (T g ) while increase in elongation, with increase in concentration of DVS in the films. These results demonstrate the plasticization tendency of DVS on EC, which was attributed to the presence of valproic acid (fatty acid) in DVS. XRD studies showed amorphous nature of the films; however, polarized microscopy revealed the presence of scattered undissolved sodium valproate crystals. The presence of a single T g established complete miscibility between valproic acid and EC. Films showed reasonable physical stability (similar T g ) at 45 °C/75% RH for 2 weeks (open condition), attributable to the similar solubility parameters of DVS and EC. FTIR and Raman spectroscopy results proved the presence of hydrogen bonding between DVS and EC.