Phase behavior of the polymer/drug system PLA/DEET

C. Sungkapreecha1, N. Iqbal1, A.M. Gohn2, W.W. Focke3, and R. Androsch1

1Interdisciplinary Center for Transfer-oriented Research in Natural Sciences, Martin Luther University Halle-Wittenberg, 06099 Halle/Saale, Germany
2School of Engineering, Penn State Behrend, 4701 College Drive, Erie, PA 16563, USA
3Institute of Applied Materials, Department of Chemical Engineering, University of Pretoria, Private Bag X20, Hatfield 0028, South Africa

The phase diagram of the binary polymer/drug system poly (lactic acid) (PLA) and N,N-diethyl-3-methylbenzamide (DEET) has been established for the purpose of screening the potential use of biocompatible and biodegradable PLA as a drug-delivery reservoir for the insect repellent DEET. Crystallization-induced solid-liquid (S-L) phase separation occurs on sufficiently slow cooling of liquid solutions containing crystallizable PLA at temperatures slightly higher than ambient temperature. Non-isothermal crystallization starts spherulitically at point-like nuclei, followed by dendritic crystal growth due to the depletion of crystallizable polymer in the solution in the late crystallization stage. Analysis of vacuum-dried crystallized systems reveals formation of intra-spherulitic scaffold-like structures with a fine structure which is tunable by the conditions of crystallization. These scaffolds then may serve as a reservoir for liquid drugs (here DEET), which are slowly released to the environment.
If crystallization of PLA is suppressed due to fast cooling or high concentration of stereodefects in racemic random PLA copolymers then liquid-liquid (L-L) phase separation into an almost pure DEET phase and a PLA/DEET solution occurs at temperatures slightly below room temperature. As such, the investigated system shows a subambient upper critical solution temperature (UCST), with the critical temperature decreasing and critical polymer concentration increasing with decreasing molar mass of the polymer. It was confirmed that the enhanced miscibility of the system components in case of low molar mass PLA is due to increased entropy of mixing. Furthermore, it appears that L-L transition temperatures are independent on the PLA stereochemistry.

[1] C. Sungkapreecha, N. Iqbal, A.M. Gohn, W.W. Focke, R. Androsch, Phase behavior of the polymer/drug system PLA/DEET, Polymer 126, 116–125 (2017).
[2] C. Sungkapreecha, M.J. Beily, J. Kressler, W.W. Focke, R. Androsch, Phase behavior of the polymer/drug system PLA/DEET: Effect of PLA molar mass on subambient liquid-liquid phase separation, Thermochim. Acta 660, 77–81 (2018).