(377e) Molecular Thermodynamic Modelling of Micellar-Assisted Drug Delivery Systems

Gow, A. S., University of New Haven
Hong, T., University of New Haven
A molecular thermodynamic model of mixed micellization is constructed for solubilization of a set of model drugs in aqueous solutions of nonionic surfactants from the polyoxyethylene glycol monoether (CiEj) family. The proposed model is an extension of a molecular thermodynamic model that was originally advanced by Blankschtein and coworkers for simple binary aqueous surfactant mixtures [1] and later applied to systems of ibuprofen with one each common nonionic, anionic and cationic surfactant [2]. The ibuprofen in this earlier approach was modelled as a simple (“pseudo”) anionic surfactant (fully dissociated at human body conditions of T=37oC and pH=7.4) with limited solubility in water and inability to micellize in water in the absence of additional surfactants. The set of model drugs in the present study includes: 1) popular “over-the-counter” formulations (e.g., ibuprofen); 2) widely used prescription drugs (e.g., simvastatin and lisinopril); and 3) therapeutic agents for severe diseases (e.g., paclitaxel). These compounds are structurally represented as “pseudo” asymmetrical Gemini surfactants consisting of a chain network of multiple hydrophilic and hydrophobic moieties.

The key property of the molecular thermodynamic modeling approach for self-assembled systems is the free energy of micellization, which for mixed ionic surfactants in water consists of six contributions including: 1) the transfer of surfactant tails or drug molecule hydrophobic moieties from bulk water to the micellar core; 2) the creation of a micellar hydrocarbon core-water interface, which accounts for the molecular architecture of the drug molecule; 3) surfactant and drug tail chain packing within the micellar core (i.e., consideration that tails are constrained at the interface); 4) surfactant and drug molecule hydrophilic head group steric repulsions; 5) electrostatic effects between charged moieties and counterions; and 6) the entropic effect of mixing various species. The Gibbs free energy of micellization is minimized with respect to core minor radius for different shapes to determine the optimum shape, size and composition of micelle including degree of counterion binding. Key output from the model includes: 1) micellar composition as a function of bulk surfactant mole fraction; 2) drug solubility as a function of surfactant mole fraction; and 3) the molar solubilization capacity (drug solubility/surfactant concentration). These features and the optimum micelle size and shape are reported for each drug-surfactant system. Finally, CiEj surfactants are ranked according to their ability solubilize each model drug in the study.


[1] S. Puvvada and D. Blankschtein, Theoretical and Experimental Investigations of Micellar Properties of Aqueous Solutions Containing Binary Mixtures of Nonionic Surfactants, J. Phys. Chem. 96, 5579-5592 (1992).

[2] B. C. Stephenson, C. O. Rangel-Yagui, A. P. Junior, L. C. Taveres, K.. Beers and D. Blankschtein, Experimental and Theoretical Investigation of Micellar Assisted Solubilization of Ibuprofen in Aqueous Media, Langmuir 22, 1514-1525 (2006).

[3] T. A. Camesano and R. Nagarajan, Micelle Formation and CMC of Gemini Surfactants: A Thermodynamic Model, Colloids and Surfaces A: Physicochemical and Engineering Aspects 167, 165-177 (2000).