Through-vial impedance spectroscopy of the mechanisms of annealing in the freeze-drying of maltodextrin: the impact of annealing hold time and temperature on the primary drying rate.
The study aims to investigate the impact of annealing hold time and temperature on the primary drying rate/duration of a 10% (w/v) solution of maltodextrin with an emphasis on how the mechanisms of annealing might be understood from the in-vial measurements of the ice crystal growth and the glass transition. The electrical impedance of the solution within a modified glass vial was recorded between 10 and 10(6) Hz during freeze-drying cycles with varying annealing hold times (1-5 h) and temperatures. Primary drying times decreased by 7%, 27% and 34% (1.1, 4.3 and 5.5 h) with the inclusion of an annealing step at temperatures of -15°C, -10°C and -5°C, respectively. The glass transition was recorded at approximately -16°C during the re-heating and re-cooling steps, which is close to the glass transition (Tg ') reported for 10% (w/v) maltodextrin and therefore indicates that a maximum freeze concentration (∼86%, w/w, from the Gordon-Taylor equation) was achieved during first freezing, with no further ice being formed on annealing. This observation, coupled to the decrease in electrical resistance that was observed during the annealing hold time, suggests that the reduction in the drying time was because of improved connectivity of ice crystals because of Ostwald ripening rather than devitrification.
Leicester School of Pharmacy, De Montfort University, Leicester, LE1 9BH, United Kingdom.
Geoff
G
Smith
Muhammad Sohail
MS
Arshad
Eugene
E
Polygalov
Irina
I
Ermolina
D005612:Freeze Drying; D011134:Polysaccharides / Q000737:chemistry*; D013057:Spectrum Analysis / Q000379:methods*; D013696:Temperature
D011134:Polysaccharides; C008315:maltodextrin
Excipients; Processing; annealing; freeze-drying; glass transition; impedance spectroscopy; lyophilisation; maltodextrin; process analytical technology (PAT)