Transport Studies of Oil-Soluble Polymers - ACS Symposium Series

Chapter 15

Transport Studies of Oil-Soluble Polymers Brian A. Harvey , Thelma M . Herrington , and Rodney Bee Downloaded by UNIV OF CALIFORNIA SAN DIEGO on December 16, 2015 | http://pubs.acs.org Publication Date: March 5, 1993 | doi: 10.1021/bk-1993-0520.ch015

1

1

2

Department of Chemistry, The University of Reading R G 6 2 A D , United Kingdom Unilever Research, Colworth Laboratory, Sharnbrook, Bedford M K 4 4 1 L Q , United Kingdom 1

2

In connection with our current studies of the factors affecting the stability of water/oil/water multiple emulsions for the food industry, we have carried out some fundamental studies of solute transfer across an oil membrane by polymeric molecules. The overall rates of transfer of a series of carboxylic acids across a polar oil (glycerol triester) was determined by using a rotating diffusion cell. The polymers used were a polyglycerol fatty acid ester and an ABA block copolymer of poly(12hydroxy)stearic acid with ethylene oxide. The effect of other oil soluble surfactants and of electrolyte in the aqueous phase on the rates of transfer was also studied. By measuring the diffusion coefficients and partition coefficient of the solute it is possible to differentiate between the contributions to the transport from the transfer at the oil/water interface and that from diffusion in the oil phase.

In a multiple emulsion two liquid phases are separated by another immiscible liquid layer. This type of system was first discovered by Seifriz (1) in studies of the phase inversion of ordinary emulsions. Since the sixties many potential applications have been suggested for water-in-oil-in-water (W/O/W) multiple emulsions. In the pharmaceutical industry, Engel (2) tried to improve the efficiency of intestinal adsorption by immobilizing insulin in the inner aqueous phase of a multiple emulsion and several workers have formulated recipes for prolonged drug delivery systems (3-5), or suggested usage as solvent reservoirs in the treatment of drug overdose cases (6, 7). A t Exxon progress has been made in the application of multiple emulsions for liquid membrane extraction processes (8). In the food industry it has potential use in the manufacture of low fat food products, such as mayonnaise, and for the controlled release of nutrients for special dietary requirements. However, more effort is required

0097-6156/93/0520-0220$06.00/0 © 1993 American Chemical Society

In Polymeric Delivery Systems; El-Nokaly, M., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1993.

Downloaded by UNIV OF CALIFORNIA SAN DIEGO on December 16, 2015 | http://pubs.acs.org Publication Date: March 5, 1993 | doi: 10.1021/bk-1993-0520.ch015

15. HARVEY E T AL.

Transport Studies of Oil-Soluble Polymers

221

to obtain fundamental information o n the factors affecting the dispersion state and stability of multiple emulsions. M a t s u m o t o et a l (9) attempted to clarify the efficiency of the hydrophobic a n d hydrophillic emulsifiers used i n a 2 step procedure of emulsifying a water-in-oil emulsion i n an aqueous surfactant solution. Florence and W h i t e h i l l (10) studied the kinetics of b r e a k d o w n a n d suggested possible mechanisms. T o m i t a et al (11) reported that the changes i n phase volume of the aqueous compartments i n W/O/W emulsions are not only brought about by the migration of water under the osmotic pressure gradient, but are partially caused by the permeation of solutes, such as glucose, across the o i l layer. In order to determine how solute transport affects the stability of W/O/W multiple emulsions, a m o d e l system, with planar interfaces, was chosen. In earlier experiments i n our laboratory (Harvey, B . , R e a d i n g University, U K , unpublished data), using a bulk W/O/W emulsion made f r o m food components, studies of solute transport were not reproducible. This multiple emulsion consisted of three phases: an internal aqueous phase with droplet diameters of 1 μπι; an o i l phase of groundnut o i l containing polyglycerol polyricinoleate (5 w t % ) ; a continuous outer-aqueous phase containing sodium caseinate (2 w t % ) . T h e o i l phase is predominantly a mixture of triglycerides containing the oil-soluble surfactant. T h e multiple emulsion was stable for 2 to 3 weeks, but the stability could be enhanced by adding electrolyte to the aqueous phase. T h e properties were affected by the relative volumes of the 3 phases, the size and distribution of the internal water and o i l droplets, the concentration of the secondary surfactant, the osmotic properties of the aqueous phase and the viscosity. Studies of solute transfer f r o m the inner to outer aqueous phases were carried out, but these met with little success, as the properties are interdependent and altering one parameter changed another. It is also difficult to separate the phases for analysis. T h e W/O/W system with planar interfaces was modelled using a R o t a t i n g Diffusion C e l l i n which the planar oil-water interfaces are supported o n a membrane filter. In order to determine the resistance to interfacial transfer for a solute, it is necessary to measure diffusion coefficients i n b o t h the o i l and aqueous phases and the oil/water partition coefficients. Experimental M a t e r i a l s . A n a l y t i c a l G r a d e reagents were used throughout unless otherwise stated. T h e triglyceride esters used were glycerol trioleate (99%) and a commercial triglyceride ester (groundnut oil) T h e polymeric surfactants used were: polyglycerol polyricinoleate; an A B A block copolymer of poly(12hydroxystearic) acid/ethylene oxide - number average molar mass 3543 ± 30 g m o l " (obtained by vapour pressure osmometry) (polyethylene oxide chain 1500 g mol" ) (12). T h e monomeric surfactants used were sucrose tristearate, sorbitan trioleate, sorbitan monooleate and glycerol monooleate. D o u b l e distilled-deionised water was used throughout and carbon dioxide free nitrogen. 1

1



222

POLYMERIC DELIVERY SYSTEMS

The Rotating Diffusion Cell. This is designed hydrodynamically so that stationary diffusion layers of k n o w n thickness are created each side of the o i l layer (13). T h e cell is shown i n Figure 1. T h e o i l layer is supported o n a porous membrane filter which divides the apparatus into 2 compartments, separating the inner and outer aqueous phases. T h e cell is mounted i n a thermostatted glass jacket. T h e central assembly is rotated by a stepper motor at constant k n o w n speeds up to 6 H z . T h e fixed slotted baffle, positioned a short distance above the filter, ensures a stationary diffusion layer. T h e 60 μπι teflon filter, of average pore size 0.2 μπι, is located by screwing the stainless steel filter holder against the steel plate attached to the perspex cylinder, leaving an exposed circular area 2 c m i n diameter. T o measure the flux of an organic acid, the inner compartment, within the perspex cylinder, was filled with the acid and the outer compartment was filled to the same level with 5 χ 10" m o l d m " N a C l solution. C a r e must be taken to ensure that no air bubbles are trapped beneath the filter a n d precautions were taken to remove a n d exclude C 0 from the solutions by w o r k i n g under nitrogen. 3

3

2

T h e flux of acid passing through the o i l membrane was monitored by maintaining the p H i n the outer compartment at 7.0 by means of a combined electrode a n d p H meter attached to a D o s i m a t automatic titrator which injects carbon dioxide-free 0.1 m o l d m " N a O H solution. 3

The Stokes Diffusion Cell. A modified Stokes Diffusion C e l l was used to determine the diffusion coefficients, D and D , of the aqueous and organic phases respectively (14). This is shown i n Figure 2. T h e stirrer and follower closely sweep both sides of a porous glass sinter at a fixed rotation speed of 2 H z to prevent stagnant diffusion layers forming. T h e nylon l i d has holes drilled for a pH-electrode, nitrogen supply and alkali delivery tube. T o determine D the lower compartment and the sinter are filled with the acid, whose diffusion coefficient is to be measured, the upper compartment is filled with 5 χ 10* m o l d m " K C 1 and the flux is measured with the pH-stat. F o r D , the lower compartment a n d the sinter are filled with a solution of the acid in o i l a n d the u p p e r compartment is filled with the oil. T h e upper compartment is sampled periodically and the concentration of the acid found by partitioning against water; the partition coefficient/concentration relationships required were determined using oscillated flasks m o u n t e d i n an air thermostat. a q

G

a q

3

3

G

Theory R o t a t i n g disc hydrodynamics are created within the cell (15,16). A stagnant layer is created o n each side of the filter, whose thickness Ζ is given by the L e v i c h equation:



15. HARVEY E T AL.

Figure A Β C D Ε F


1. T h e R o t a t i n g Diffusion C e l l . Thermostatted outer jacket Perspex cylinder Teflon baffle Slots Pulley Stainless steel filling tube

G H J Κ L

Rubber bung Lid Stainless steel filter holder M e m b r a n e filter Stainless steel plate

Rubber

Nylon

Upper

Clutch

Lid

Compartment

Magnetic

Stirrer

Sinter. Follower

Lower

Compartment

Figure 2. C e l l for measurement of diffusion coefficients.


223

224


Ζ -

D^

6

βη"

ω"

3

(1)

1/2

where η is the kinematic viscosity, D is the diffusion coefficient i n aqueous solution, ω is the rotation speed, β is a constant. T h e rate of transfer of the diffusing solute species from the inner to the outer compartment is given by a q

J

-

kAc


(2)

where A is the area of the filter, c is the bulk concentration of the solute i n the inner compartment, k is given by 1 k

_2Z "

D

2

+

_K1

+

ak.,

a q

aD

(3)

0

T h e significance of the 3 terms o n the right hand side of equation 3 are: 1

2 Z / D describes diffusion through the 2 stagnant aqueous diffusion layers of thickness Z ;

2

2/ak.j is the contribution from interfacial transfer at the 2 oil-water boundaries; α is the cross-sectional area of the pores divided by the filter area and k_j is the rate constant for the species M defined by

a q

M (org)

^

1

Κ -

M(aq)

k_!

k

_L

(4)

k-1

3 K l / a D is the contribution from the diffusion of the solute through the o i l phase i n the filter; Κ is the partition coefficient, 1 is the filter thickness a n d D the diffusion coefficient i n the o i l phase. B y substituting equation 1 i n equation 3, equation 5 is obtained Q

Q

6

/Z

* - 2βη" D* k

H

«*

1

of '

2 +

2 ak_!

+

Kl aD

v

c

'

and it follows that a plot of 1/k against ω* , a L e v i c h plot, has a n intercept of: 2/ak.! + K l / a D . Interfacial transfer + Diffusion i n the o i l phase 1/2

G

A typical value for Z , the thickness of the stagnant layer, is 30 to 40 μπι. T h e results were fitted to a L e v i c h plot with a theoretical slope given by equation 5. T o obtain the rate constant for transfer at the oil/water interface, k. it is necessary to determine the diffusion coefficient, D i n the o i l phase a n d the partition coefficient, K . A l s o the first t e r m of the intercept must be significant c o m p a r e d with the second. v

Q


15.

HARVEY E T AL.

Transport Studies of Oil-Soluble

Polymers

225


Results T h e r e has been n o systematic literature study o f the interfacial transfer o f small molecules. T h e effect o f the length o f the alkyl chain o f the alkanoic acids and o f the temperature o n the rate o f transfer were studied. T h e rotating diffusion cell was set running for 1 hour at a l o w speed to equilibrate. T h e speed was then successively increased i n 4 steps from 1.2 to 4 H z , maintaining each speed for 30 minutes, to obtain the L e v i c h plot for each system. K i n e t i c data were obtained at 25.00 ± 0.01 °C. T h e effect o f various additives, polymers and surfactants, dissolved i n the membrane b o u n d o i l phase o n the rate o f transfer o f different solutes, o f varying degrees o f polarity, was investigated. F o r the o i l phase o f triglyceride ester containing 5 % by weight o f polyglycerol polyricinoleate the L e v i c h plot is shown i n Figure 3. T h e results show that there is a progressive increase i n transfer rate with increasing chain length o f the acid. T h e results are reproducible: for example for 4 runs with valeric acid the error i n the intercept is +. 2 % . U s i n g the pure triglyceride ester, glycerol trioleate, as the o i l phase increased the rate o f transport by 5%. T h e effect o f changing the ionic strength o f the aqueous phase was studied. T h e L e v i c h plots for the transport o f valeric acid through the same oil phase but increasing the concentration o f electrolyte i n the aqueous phase f r o m zero to 0.4 m o l d m " is shown i n Figure 4. T h e effect o f temperature o n the transport o f valeric acid is shown i n Figure 5 over the temperature range 25 to 45 °C. T h e effect o f the presence o f dissolved polymer i n the o i l phase was investigated. It was found that a 5 w t % concentration o f polyglycerol polyricinoleate slowed down the transport o f valeric acid (Figure 6), whereas a 5 w t % concentration o f the block copolymer increased the rate. T h e effect of several nonionic surfactants, dissolved i n the o i l phase, was determined. G l y c e r o l monooleate, 5 w t % , decreases the rate o f transport o f valeric acid through the triglyceride ester (Figure 6). A temperature o f 45 °C was used to enhance the solubility o f the surfactants; it was found that sucrose tristearate (1 w t % ) decreased the rate o f transport o f valeric acid, whereas sorbitan trioleate (1 w t % ) and sorbitan monooleate (1 w t % ) increased it, the latter quite significantly (Figure 7). T h e transport o f acetic and formic acids through the triglyceride o i l membrane was very slight and not reproducible, also the L e v i c h plots were not straight lines. T h e triglyceride ester o i l phase was found to be impermeable to the following polar solutes: sorbitol; glucose; raffinose; glycine; leucine; sodium chloride; potassium chloride; b a r i u m chloride; calcium chloride and caesium chloride. It was also impermeable to the following acids which are allowed i n foodstuffs: lactic; malic; tartaric; citric; fumaric; ascorbic; sorbic and benzoic. 3



226

~


τ—

h I

W

Τ I

η

fcd Ο

Τ

a

w

π

RJ ! τ ΐ i

η

Ο

·•

Β—

1

1

+

4. ,

0.2

Rotation S p e e d ( ω / Η ζ )

0.4

0.6

0.8

2

Figure 3. L e v i c h Plot of n-alkyl carboxylic acids through triglyceride ester containing 5 w t % polyglycerol polyricinoleate at 25 °C: Ο Propanoic acid; · Butyric acid; • V a l e r i c acid; • C a p r o i c acid.

1.6-r 1 41 21.00.8CO

0.6-

Ε

0.4-

Ο r-

0.2-

(Ο

0

0.2 Rotation Speed ( ω / Η ζ )

0.4 1 / 2

Figure 4. L e v i c h Plot of valeric acid through triglyceride ester containing 5 w t % polyglycerol polyricinoleate, as a function o f the N a C l concentration, at 25 °C: Ο no N a C l ; · 0.1 M N a C l ; • 0.2 M N a C l ; • 0.4 M N a C l .


1.0

15. HARVEY E T AL.

Transport Studies of OU-Soluble Polymers


1.6

Rotation Speed ( ω / H z ) Figure 5. L e v i c h Plot of valeric acid through triglyceride ester containing 5 w t % polyglycerol polyricinoleate, as a function of the temperature: Ο 25.0 °C ; · 30.0 °C; • 37.0 °C; • 45.0 °C.

0.8

0 0.2 Rotation S p e e d

0.4 (ω/Ηζ)" 2 1/

Figure 6. L e v i c h Plot of valeric acid through triglyceride ester containing different surfactants at 25 °C: Ο 5 w t % polyglyceryl polyricinoleate; · 5 w t % glycerol monooleate; • n o surfactant; • 5 w t % block copolymer; L e v i c h slope.



228

POLYMERIC DELIVERY

SYSTEMS

Figure 7. L e v i c h Plot of valeric acid through triglyceride ester containing different surfactants at 45 °C: Ο 1% sucrose tristearate; • no surfactant; • 1 w t % sorbitan trioleate; • 1 w t % sorbitan monooleate; L e v i c h slope.



15. HARVEY E T AL.

229

Discussion T h e intercept of the L e v i c h plot, 2 / a k + K l / a D , gives the contribution of the transport at the oil-aqueous interfacial barrier (first term) and the transport by diffusion through the o i l phase (second term). It is convenient to consider these terms as the resistance to transport of the acid through the cell. T h u s the first term is R j , the resistance due to interfacial transfer, a n d the second term is R , the resistance due to diffusion. T h e diffusional resistance term can be calculated from our experimental measurements of the Distribution Coefficient, K , and the diffusion coefficient i n the o i l phase, D . T h e resistance caused by transfer at the oil-aqueous interface, R j , is then obtained as the difference between the experimental L e v i c h intercept a n d R . T h e overall resistance to transport decreases with increasing chain length, for the triglyceride o i l with polyglycerol polyricinoleate (5 w t % ) . T h e diffusional resistance decreases with increasing length of the alkyl chain, so that the interfacial resistance also decreases f r o m butyric to caproic acid (Table I). B o t h these trends are consistent with the increasing nonpolar nature of the acids. 4

G


D

G

D

Table I. T h e contributions of transfer at the oil/water interface and of diffusion through the o i l phase, to the rate of transport of the n-alkyl carboxylic acids through the o i l phase of triglyceride ester containing 5 w t % of polyglycerol polyricinoleate Acid

Ru/10 m

Propionic Butyric Valeric Caproic

15.1 4.6 1.4 0.6

26.6 17.4 11.4 8.4

Valeric Acid No NaCl 0.1 M N a C l 0.2 M N a C l 0.4 M N a C l

1.42 1.39 1.36 1.30

11.4 9.3 8.8 8.1

Valeric Acid 25 °C 30 °C 37 °C 45 °C

1.42 1.02 0.70 0.46

11.4 6.9 4.5 3.2

5

1

s

R,/10 m s 5


1


230


T h e effect of increasing the ionic strength of the aqueous phase (Figure 4) shows that the resistance to overall transport, given by the intercept o f the L e v i c h plot, decreases with increasing sodium chloride concentration. F r o m T a b l e I it can be seen that the diffusional contribution to the transport only changes very slightly with electrolyte concentration. Thus it is the interfacial contribution to the transport which is increased by increasing the concentration o f electrolyte. A s shown by the intercepts of the L e v i c h plot of Figure 5, increasing the temperature has a large effect o n the transport o f valeric acid. B o t h the overall resistance to transport and the diffusional resistance decrease with increasing temperature (Table I). T h a t transport of valeric acid is slowed down by the addition of polyglycerol polyricinoleate to the o i l phase (Figure 6) is probably caused by the increased viscosity of the oil. T h e transport of the acid is facilitated by the block copolymer (Figure 6), possibly by reverse micelles acting as carriers although the effect is very slight. O f the monomeric surfactants (Figure 6 and 7), only sorbitan trioleate markedly facilitated the transport of the valeric acid. A g a i n reverse micelles may be acting as carriers. Conclusions T h e rotating diffusion cell provides a n exact method for determining the rates of transport of molecules from one aqueous phase to another through a n o i l membrane. T h e rate constant for transport increased, with increasing number of carbon atoms i n the alkyl chain, for the 4 straight chain alkyl carboxylic acids, propanoic to caproic. Solute molecules that were highly polar d i d not pass through the membrane. T h e effect o n the rate of transfer of several o i l soluble polymeric and monomeric surfactants was studied but no evidence for facilitated transport was found. Acknowledgments W e thank both S E R C and U n i l e v e r for financial assistance towards this research. Literature Cited

1 2 3 4 5 6 7

Seifriz, W. J. Phys. Chem., 1925, 29, 738. Engel, R. H.; Riggi, S. J.; Fahrenbach, M . J. Nature, 1968, 219, 856. Taylor, P. J.; Miller, C. L.; Pollock, T. M.; Perkins F. T.; Westwood, M . A. J. Hygienics Cambridge, 1969, 67, 485. Benoy, C. H.; Elson, L. Α.; Schneider, R. Br. J. Pharmacol., 1972, 45, 135. Whitehill, D. Chemist Druggist, 1980, 213, 130. Frankenfeld, J. W.; Fuller, G. C.; Rhodes, C. T. Drug Dev. Commun., 1976, 2, 405. Chiang, C.; Fuller, G. C.; Frankenfeld, J. W. J. Pharm. Sci.,1978, 67, 63.


15. HARVEY ET AL.

8

9


10 11 12 13 14 15 16

Transport Studies of Oil-Soluble

Polymers

231

Li, N . N.; Shrier, A. L. In Recent Developments in Separation Science; Li, Ν. N., Ed.; Chemical Rubber Co: Cleveland, Ohio, 1972; Vol.1; pp 163-181. Matsumoto, S.; Kita, Y.; Yonezawa, D. J. Coll. Interface Sci., 1976, 57, 353. Florence, A. T.; Whitehill, D. J. Coll. Interface Sci., 1981, 79, 243. Tomita, M.; Abe, Y.; Kondo, T. J. Pharm. Sci., 1982, 71, 268. Aston, M . S.; Bowden, C. J.; Herrington, T. M.; Sahi, S. S. J. Am. Oil Chem. Soc., 1985, 62, 1705. Riddiford, A. C. Adv. Electrochem and Electrochem Eng., 1966, 4, 47. Stokes, R. H . J. Am. Chem. Soc., 1950, 72, 763. Levich, V. G. Physicochemical Hydrodynamics; Prentice Hall: Englewood Cliffs, New Jersey, 1962; pp 60-72. Albery, W. J.; Couper, A. M.; Hadgraft, J. and Ryan, C. J. Chem. Soc., Farad. Trans.1,1974, 70, 1124.

R E C E I V E D October 1, 1992


Transport Studies of Oil-Soluble Polymers - ACS Symposium Series

Recommend Documents