Moisture sorption by polymeric excipients commonly used in amorphous solid dispersion and its effect on glass transition temperature: I. Polyvinylpyrrolidone and related copolymers.

Moisture plays a critical role in the stability of amorphous solid dispersions (ASD) as it can lower the glass transition temperature (T) and thereby increase molecular mobility resulting in drug crystallization. A systematic study on moisture sorption by four polyvinylpyrrolidone (PVP) having different molecular weights (Kollidon® 12, 17, 30, and 90) and two related copolymers (Kollidon® VA64; Soluplus®) was conducted at 25 and 40 °C as a function of relative humidity to determine effects of absorbed moisture on T and potential stability of ASDs. A VTI dynamic moisture sorption analyzer was used, where experimental conditions were first established such that equilibrium was reached and there was no significant hysteresis loop between sorption and desorption isotherms. The PVPs had identical moisture sorption profiles and were highly hygroscopic, reaching 22-24% and 41-42% w/w moisture at 25 °C/60% RH and 25 °C/80% RH, respectively. Kollidon® VA64 and Soluplus® were relatively less hygroscopic, reaching, respectively, about half and one-fourth the moisture content of PVPs at 25 °C/60% RH. Moisture sorption at 40 °C was relatively lower than that at 25 °C. The high moisture sorption drastically decreased T of polymers, which roughly agreed with theoretical calculations based on the Gordon-Taylor/Kelley-Bueche equation, although deviation occurred, possibly due to hydrogen bonding between polymer and moisture.