Drug Delivery System: Micelle for Water-Insoluble Drugs

Nov 8, 2019
Applications: BiopharmaDrug Delivery
Instruments: NanoBrook Series

Vitamin E TPGS, d-α-tocopherol polyethylene glycol 1000 succinate, is a surfactant that can be used for drug delivery. TPGS has a molecular structure of a typical amphiphile. Due to its large lipophilic and hydrophilic portions, the Critical Micelle Concentration (CMC) is relatively low. Thus, it is a good emulsifier for a wide range of water-oil immiscible systems. In addition, there are no safety concerns for oral use at 1,000 gm/kg/day in lab animals. [National Cancer Institute, One-Year Chronic Oral (Intubation) Study in Dogs and Rats. National Institute of Health, 1994.]

The micelle forms in water due to the polar hydrophilic head of polyethylene glycol (n averages 22 to 23) and nonpolar lipophilic tail of d-α-tocopherol are the signature elements of molcules that form micelles. Average molecular weight is 1,513 g/mol. Its ability to form micelles and solubilize poorly- and non-soluble water compounds makes it an excellent vehicle for drug delivery of APIs with these characteristics. Increased adsorption and bioavailability result when TPGS is used in many situations.

image of TPGS molecule

Sample Preparation

TPGS is a solid, waxy substance at room temperature. 190 mg was gently heated until melted. It was slowly poured into 100 mL of water preheated to 75 °C while stirring. While cooling, the solution was stirred for two hours. Samples were filtered three times through a 20 nm Anotop. Since micelles form spontaneously above the CMC, this provided an excellent method for clean light scattering samples without the worry of shear degradation. CMC as determined by surface tension measurements is approximately 0.02% wt/vol. Size measurement of micelle carried out at 0.19% wt/vol, well above the CMC, but well below the several percent concentration when non-spherical micelles begin to form.

iamge of vitamin E TPGS graph

DLS size measurements using the NanoBrook 90Plus are shown above. Two, five minute measurements agree very well with an Effective Diameter of 10.7 nm each and very similar polydispersity indices averaging 0.054 indicating a modestly narrow size distribution (one of the measurements shown above).