Study of the physicochemical properties and stability of solid dispersions of loperamide and PEG6000 prepared by spray drying.
Solid dispersions of PEG6000 and loperamide-a poorly water-soluble agent-were prepared by spray drying. Their physicochemical properties were evaluated immediately after preparation. The dissolution was higher than that of pure crystalline loperamide. DSC- and XRD-measurements revealed that in the dispersions, loperamide is partially present in the crystalline state. A eutectic state diagram was obtained. The samples containing 20% loperamide were stored under different conditions (40 degrees C and 0% RH, 25 degrees C and 52% RH, 4 degrees C and 0% RH) to investigate their stability as a function of time. The dissolution properties deteriorate upon storage at high temperature (40 degrees C and 0% RH) and in conditions of higher relative humidity (25 degrees C and 52% RH). The DSC-curves clearly indicate an increase in the amount of crystalline compound under these conditions. From these observations it could be concluded that loperamide, which is partially crystalline and partially amorphous in the freshly prepared samples, continues to crystallize under these conditions, resulting in progressively poorer dissolution properties.
Weuts
Ilse
I
Laboratorium voor Farmacotechnologie en Biofarmacie, University of Leuven, Leuven, Belgium.
Kempen
Dieter
D
Verreck
Geert
G
Decorte
Annelies
A
Heymans
Koen
K
Peeters
Jef
J
Brewster
Marcus
M
Van den Mooter
Guy
G
D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003460:Crystallization; D004355:Drug Stability; D008139:Loperamide / Q000032:analysis* / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000032:analysis* / Q000737:chemistry*
D011092:Polyethylene Glycols; D008139:Loperamide