Title

Effect of excess surfactant on transport of surface-active model drugs and emulsion stability in triphasic systems

Date of Completion

January 2000

Keywords

Chemistry, Pharmaceutical|Health Sciences, Pharmacy

Degree

Ph.D.

Abstract

The overall objective of this research are to predict transport of model drugs in triphasic (oil, water and micellar) emulsion system using various physicochemical parameters and mathematical models and to determine the effect of surface—active model drugs on transport in triphasic emulsions and on emulsion stability. Excess surfactant is present in most emulsions in the form of monomers and micelles to aid the stability of these systems. Excess surfactant may alter the kinetics of drug release by: micellar solubilization, alteration of the drug partitioning process, and drug/surfactant complexation. Surface—active drugs may associate with the surfactant and may alter the interfacial area, emulsion stability and transport kinetics of the drugs across the emulsion interface. A range of model drugs with similar structures, different lipophilicities and different surface—activities were selected to investigate the influence of excess surfactant on model drug transport and emulsion stability in triphasic systems. Phenylazoaniline, Benzocaine, Phenobarbital and Barbital were investigated. Light mineral oil was chosen as the oil phase. An ionic surfactant, cetyltrimethylammonium bromide and a nonionic surfactant, polyoxyethylene (10) oleyl ether were chosen to determine the effect of the ionic nature of the surfactant on model drug transport and emulsion stability in triphasic systems. Model drug transport in the triphasic systems was investigated using side-by-side diffusion cells mounted with hydrophilic dialysis membranes (molecular weight cutoffs 1 KD and 50 KD) and bulk equilibrium reverse dialysis bag method. The bulk equilibrium reverse dialysis bag method involves infinite dilution of the emulsions in a continuous phase and the model drugs are released into suspended dialysis bags. Emulsion stability was determined by droplet size analysis as a function of time and temperature using photon correlation spectroscopy and a light blockage technique. Violation of sink conditions during the transport studies occurred using the side-by-side diffusion cell method. This limitation was overcome using the bulk equilibrium reverse dialysis bag technique. The transport rate of the model drugs in triphasic systems were affected by the ionic nature of the surfactants, model drug surface—activity and lipophilicity. Mathematical models were developed using Fick's first law and consecutive rate equations. The models were predictive of the experimental data. ^