Role of water in the physical stability of solid dosage formulations.
The interaction of moisture with pharmaceutical solids is highly crucial to an understanding of water-based processes, for example, manufacturing processes or prediction of solid dosage form stability and shelf life. Both the active pharmaceutical ingredient (API) and excipients in the formulation have different moisture sorption properties that can result in unexpected processing-induced phase transitions and they can affect solid-state phase transitions in the final dosage forms. The character of excipient effects on the stability of formulation. Phase transformations in formulations can lead to instability in physicochemical, biopharmaceutical, and processing properties of products. The aim of the present study was to investigate the water sorption properties of different excipients, model the sorption isotherms, examine the phase transitions, and identify differences of excipients in solid dosage form stability using dynamic vapor sorption analysis, near-infrared spectroscopy, and X-ray diffraction methods. The thermal processing was carried out with a variable temperature X-ray powder diffractometer to compare the dehydration behavior of wet excipients and evaluate solid-state properties during heating. These results showed that despite some limitations, moisture sorption isotherms of excipients are useful in predicting solid-state stability, interactions at early stages of formulation development, and effects of moisture on physicochemical properties of the final dosage forms.
Airaksinen
Sari
S
Pharmaceutical Technology Division, Faculty of Pharmacy, University of Helsinki, Finland. sari.airaksinen@helsinki.fi
Karjalainen
Milja
M
Shevchenko
Anna
A
Westermarck
Sari
S
Leppänen
Ella
E
Rantanen
Jukka
J
Yliruusi
Jouko
J
D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D003460:Crystallization; D003890:Desiccation; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D044367:Phase Transition; D019265:Spectroscopy, Near-Infrared; D013213:Starch / Q000737:chemistry; D013696:Temperature; D013997:Time Factors; D014867:Water / Q000737:chemistry*; D014961:X-Ray Diffraction
D005079:Excipients; D004364:Pharmaceutical Preparations; D014867:Water; D002482:Cellulose; D013213:Starch; C008079:hydroxypropylcellulose; C109691:microcrystalline cellulose