Nozzle_Poster_AIChE00

1
Polymer Stabilized Emulsions For Drug
Delivery Effect of Polymer and Oil Choice Ashley
Bourgault1, Michael Brunetti1, Matthew Regan1,
Anne St Martin2, Alain Durand3, Michèle
Léonard3, Terri Camesano1, W. Grant
McGimpsey2 1Department of Chemical Engineering,
Worcester Polytechnic Institute, Worcester, MA
01609 2Department of Chemistry and Biochemistry,
Worcester Polytechnic Institute, Worcester, MA
01609 3Laboratoire de Chimie Physique
Macromoléculaire, Ecole Nationale Supérieure des
Industries Chimiques

OIL PARTITION COEFFICIENT
ABSTRACT
A collaboration between WPI and ENSIC was
undertaken to investigate the properties of
emulsions as a drug delivery system. The use of
biocompatible amphiphilic polymers as emulsifiers
for controlled drug delivery is a relatively new
technology. The emulsifier acts as a barrier
between phases in oil-in-water emulsions to
increase stability. Oil soluble drug substances
can then be encapsulated within the oil
nanoparticles where the polymer surfactants help
to control the drug release into a biological
system over time. The goal of this project was
to research the stabilization and drug release
kinetics of two modified amphiphilic polymers,
dextran (DexC6) and alginate. The most stable
emulsions were formed with a DexC6 aqueous
concentration of 40g/L in a system of 40
octyldodecanol oil volume. Experimentation
yielded consistent drug release kinetics for both
polymers, that encapsulated lidocaine is released
at a much slower rate than free lidocaine. This
conclusion encourages further research into drug
delivery through emulsion systems.
The partition coefficient (Kp) was determined
using UV-visible spectroscopy. Four different
types of oil were used for this study. Saturated
lidocaine in a dilute NaOH solution was mixed
well with each oil, and allowed to settle and
reach equilibrium. Finally, the aqueous phase
was analyzed for absorbance and the results are
as shown. Octyldodecanol showed the highest Kp
in each case.
Partition Coefficient Calculation
Kp C drug in oil / C drug in solvent
Octyldodecanol Verification
4 more trials were run initially using 6 mg/mL
lidocaine in octyldodecanol. Consistent results
were obtained Kp (octyldodecanol) 62 3
INTRODUCTION

• Traditional Drug Delivery
• Intravenous and oral administration
• First order kinetics
• Problems with toxicity and repeated dosing

• Ideal Drug Delivery
• Controlled, slow release kinetics
• Zero order kinetics
• Can be achieved through polymer stabilized
  emulsions

EMULSIFICATION
Emulsions made with either modified dextran or
alginate polymers, 10-4M NaOH solution or 10-2M
NaCl solution, octyldodecanol, and
lidocaine. Dextran emulsions aqueous polymer
concentrations of 30g/L and 40 g/L, a 40 oil
fraction, and an oil lidocaine concentration of
25g/L. Alginate emulsions aqueous polymer
concentrations varied from 0.1 g/L to 4.0 g/L and
oil fractions that ranged from 10 to 30 with an
oil lidocaine concentration of 25 g/L.
EMULSION STABILITY
Emulsion degradation was marked by the increase
in the particle size of the emulsion with time.
Emulsions were also artificially aged by use of a
centrifuge and freeze dried and reconstituted to
further test their stability.
Lidocaine Encapsulated Emulsions, 40g/L DexC6

OBJECTIVES
DexC6 Concentrations of 30g/L and 40g/L

• Synthesize dextran and alginate polymers for
  structural analysis and use in all project
  experiments
• Determine best oil for emulsion preparation using
  partition coefficient data
• Optimize parameters for emulsion particle
  stability
• Study drug release kinetics to confirm that
  polymer presence helps to control lidocaine
  release

POLYMER PREPARATION
Alginate Emulsion Particle Sizes Over Time
Dextran is a natural polysaccharide molecule that
was chosen for drug delivery research because it
is biocompatible and biodegradable. It is a
hydrophilic molecule that is reacted with
epoxyoctane to obtain a amphiphilic polymer. The
reaction substitutes hexane groups onto the
monomer units. NMR is used to determine the
degree of substitution of the polymer. The
molecule used for experimentation was
approximately 20 substituted DexC6.
Unsubstituted Dextran Monomer
Substituted Dextran Monomer
NMR spectrum for degree of substitution analysis
LIDOCAINE RELEASE KINETICS

• Modified Dextran
• 10 mL emulsion with 40 oil
• 25 g/L lidocaine in oil, 40 g/L DexC6 in aqueous

• Modified Alginate
• 30 mL emulsion 10 oil
• 25 g/L lidocaine in oil, 1.4 g/L alginate in
  aqueous

ALGINATE SYNTHESIS
Alginate is a naturally occurring biopolymer
consisting of linear, unbranched polysaccharides
that is extracted from brown algae. In addition,
alginate matrices are very biodegradable and will
eventually dissolve under normal physiological
conditions.
CONCLUSIONS

• Most stable emulsion was formed with 40 oil
  volume, 40 g/L DexC6 (Particle sizes of
  approximately 300 nm)
• Octyldodecanol was the best oil based on
  partition coefficient experiments
• Drug release kinetics were more controlled when
  emulsions were used

Goal was to obtain 8 fixation of C12 chains on
the alginate backbone Achieved at rate of
fixation of 5 C12 chains on alginate
RECOMMENDATIONS

• Discontinue the use of dilute NaOH as the aqueous
  phase
• Model lidocaine release experiments based on
  convective mass transfer
• Reevaluate dialysis purification step of dextran
  synthesis procedure