Title

Effect of the Thermodynamic Activities of the Unionized and Ionized Species in Nanoemulsion on Drug Permeation across Porcine Small Intestine

Poster Number

4

Lead Author Affiliation

Department of Pharmaceutics & Medicinal Chemistry

Introduction

Oil in water (o/w) nanoemulsion is a two phase dispersed system and the oil phase can incorporate poorly water soluble drugs to form a liquid dosage form. The role of thermodynamic activities of the ionized drugs in solution when permeating through various barriers was explained by our group previously, however, the mechanism of the ionized and unionized drug permeation from nanoemulsion has not been fully elaborated from thermodynamic activity aspects.

Purpose

To delineate the role of thermodynamic activities of the unionized and ionized species in nanoemulsion on permeation of the acidic drug across porcine small intestine.

Method

Nanoemulsion was prepared using medium chain triglyceride oil and Span80/Tween80 mixtures. Poorly water soluble acidic drug, ketoprofen, was used as a model drug. Three levels of drug loading were used to study the drug partition in nanoemulsion. The drug in nanoemulsion was separated into the oil phase and the aqueous phase by ultrafiltration. The pH of the aqueous phase of nanoemulsion (pHaq) was measured. The fraction of ionized and unionized species was calculated based on the Henderson-Hasselbalch equation. The thermodynamic activity was expressed as the degree of saturation (DS). DS in the oil phase of nanoemulsion (DSoil) was calculated by dividing the drug concentration by the solubility in the oil phase. DS of unionized species (DSu) and ionized species (DSi) in the aqueous phase of nanoemulsion was calculated by dividing the unionized or ionized drug concentration by the intrinsic solubility and the maximum solubility, respectively. In vitro permeation studies were conducted using the side-by-side diffusion cells with the porcine small intestine at 37°C. The maximum fluxes (Jmax) of unionized and ionized species were determined from the permeation studies using the saturated solution at different pH. The total flux (JT) was obtained from the experiment and simulated based on the fluxes of unionized species (Ju) and ionized species (Ji) using the equation JT=Ju+Ji=DSuJumax+DSiJimax.

Results

As the DSoil increased, the pHaq decreased due to the increase in the net amount of drug partitioning from the oil phase to the aqueous phase. The decrease in pHaq led to an increased DSu while DSi remained almost constant. JT increased as DSu increased while DSi remained constant and Ju increased while Ji remained constant. As the DSu increased, the relative contribution of ionized species (Ji/JT) decreased from 81.0% to 32.4%.

Significance

The flux across the porcine small intestine was determined by formulation and the thermodynamic activities of both ionized and unionized species of a acidic drug in the aqueous phase of nanoemulsion.

Location

DeRosa University Center, Stockton campus, University of the Pacific

Format

Poster Presentation

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Apr 25th, 2:00 PM Apr 25th, 4:00 PM

Effect of the Thermodynamic Activities of the Unionized and Ionized Species in Nanoemulsion on Drug Permeation across Porcine Small Intestine

DeRosa University Center, Stockton campus, University of the Pacific

Oil in water (o/w) nanoemulsion is a two phase dispersed system and the oil phase can incorporate poorly water soluble drugs to form a liquid dosage form. The role of thermodynamic activities of the ionized drugs in solution when permeating through various barriers was explained by our group previously, however, the mechanism of the ionized and unionized drug permeation from nanoemulsion has not been fully elaborated from thermodynamic activity aspects.