Time-temperature superposition principle for the kinetic analysis of destabilization of pharmaceutical emulsions.

Abstract

The time-temperature superposition principle (TTSP) was applied to the destabilization kinetics of a pharmaceutical emulsion. The final goal of this study is to predict precisely the emulsion stability after long-term storage from the short-period accelerated test using TTSP. As the model emulsion, a cream preparation that is clinically used for the treatment of pruritus associated with chronic kidney disease was tested. After storage at high temperatures ranging from 30 to 45 °C for designated periods, the emulsion state was monitored using magnetic resonance imaging, and then the phase separation behaviors observed were analyzed according to the Arrhenius approach applying TTSP. The Arrhenius plot showed a biphasic change around 35 °C, indicating that the separation behaviors of the sample were substantially changed between the lower (30-35 °C) and higher (35-45 °C) temperature ranges. This study also monitored the coalescence behavior using a backscattered light measurement. The experiment verified that the destabilization was initiated by coalescence of oil droplets and then it eventually led to obvious phase separation via creaming. Furthermore, we note the coalescence kinetics agreed well with the phase separation kinetics. Therefore, in the case of the sample emulsion, the coalescence behavior has a dominant influence on the destabilization process. This study offers a profound insight into the destabilization process of pharmaceutical emulsions and demonstrates the promising applicability of TTSP to pharmaceutical research.

• Authors: Takahiro Tsuji, Koji Mochizuki, Kotaro Okada, Yoshihiro Hayashi, Yasuko Obata, Kozo Takayama, Yoshinori Onuki
• Journal: International journal of pharmaceutics (Int J Pharm) Vol. 563 Pg. 406-412 (May 30 2019) ISSN: 1873-3476 [Electronic] Netherlands
• PMID: 30978488 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 Elsevier B.V. All rights reserved.

Chemical References

• Emulsions
• Plant Oils
• Menthol
• Thymol
• Ethanol
• Camphor
• Diphenhydramine

Topics

• Camphor (chemistry)
• Diphenhydramine (chemistry)
• Drug Stability
• Emulsions (chemistry)
• Ethanol (chemistry)
• Kinetics
• Mentha
• Menthol (chemistry)
• Plant Oils (chemistry)
• Skin Cream (chemistry)
• Temperature
• Thymol (chemistry)
• Time Factors