Effect of a counterion on the glass transition temperature (T(g)') during lyophilization of ganciclovir salt forms.
This manuscript deals with the effect of a counterion on the glass transition temperature for lyophilization of ganciclovir salts. Salt forms of ganciclovir, namely, sodium, potassium, rubidium, and cesium salts, were prepared by an in situ technique and analyzed by modulated differential scanning calorimetry (MDSC) for the determination of the critical process parameter for lyophilization. Nonionized ganciclovir and its salt forms showed a glass transition (T(g)') in the reversing MDSC signal, confirming their amorphous nature. T(g)' of the nonionized ganciclovir and ganciclovir sodium, potassium, rubidium, and cesium salts followed the order: sodium salt (-34.94°C) > nonionized ganciclovir (-40.15°C) > potassium salt (-46.23°C) > rubidium salt (-49.95°C) > cesium salt (-53.62°C). The analysis of the freezable water content for ganciclovir and its salts showed the trend: pure water > nonionized ganciclovir > potassium salt ∼ sodium salt > rubidium salt > cesium salt. This showed that a majority of water in the salts is present as an unfrozen fraction, thus leading to a lowering of T(g)' because of the plasticizing effect of unfrozen water. Density functional theory (DFT) further suggested a positive contribution of the strength of intra- and intermolecular force of interactions to the T(g)' value, with a higher intramolecular and intermolecular force of interaction leading to a higher T(g)'.
Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), SAS Nagar, Mohali, Punjab 160 062, India.
Lokesh
L
Kumar
Ankit
A
Baheti
Arvind K
AK
Bansal
D002152:Calorimetry, Differential Scanning; D005612:Freeze Drying / Q000379:methods*; D015774:Ganciclovir / Q000737:chemistry*; D005898:Glass / Q000737:chemistry*; D012492:Salts / Q000737:chemistry*; D044366:Transition Temperature
D012492:Salts; D015774:Ganciclovir