Effect of moisture on polyvinylpyrrolidone in accelerated stability testing.
Accelerated stability studies are a common approach for predicting the long-term stability of pharmaceutical formulations. However, in this study, a slowing of dissolution was observed for a formulation following storage at elevated temperature and humidity. The moisture sorption isotherm for the binder, polyvinylpyrrolidone (PVP), shows absorption of a significant quantity of water on exposure to elevated humidity. Modulated temperature differential scanning calorimetry (mDSC) has been used to demonstrate that moisture uptake will depress the glass transition temperature (Tg) of PVP to the conditions used in accelerated stability studies. Exposure to elevated temperature and humidity resulted in a change in the PVP from the glassy to the rubbery state. This conversion produces a change in the dissolution profile. Long-term stability studies conducted at temperatures and humidities below the Tg, would not have induced this change.
Fitzpatrick
Shaun
S
Merck Sharp and Dohme, Hertford Road, Hoddesdon, EN11 9BU, UK. shaun_fitzpatrick@merck.com
McCabe
James F
JF
Petts
Catherine R
CR
Booth
Steven W
SW
D002482:Cellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D004355:Drug Stability; D004356:Drug Storage; D005079:Excipients / Q000737:chemistry; D006361:Heating; D006813:Humidity; D011205:Povidone / Q000737:chemistry*; D011237:Predictive Value of Tests; D012995:Solubility; D013607:Tablets; D013997:Time Factors; D014867:Water / Q000737:chemistry
D005079:Excipients; D013607:Tablets; D014867:Water; D002482:Cellulose; C008079:hydroxypropylcellulose; D011205:Povidone