J. of Supercritical Fluids 28 (2004) 225–231

Solubility behavior of ethyl cellulose insupercritical fluid solvents

Dan Li, Mark A. McHugh∗

Department of Chemical Engineering, Virginia Commonwealth University, Richmond, VA 23284, USA

Received 16 September 2002; received in revised form 24 January 2003; accepted 21 February 2003

Abstract

Solubility data to 180◦C and 1200 bar are reported for∼1.0 wt.% ethyl cellulose (50% ethoxyl content, 2.5 average degree ofsubstitution) (EC) in neat supercritical fluid (SCF) chlorodifluoromethane (F22); difluoromethane; 1-chloro-1,1-difluoroethane;1,1-difluoroethane; and dimethyl ether (DME). The pressures needed to dissolve EC in the polar fluorocarbons decreases withincreasing solvent size. The exception in this trend is F22 which is the best fluorocarbon solvent of the series likely due to itsability to hydrogen bond to the oxygens in EC. Data are also reported for EC in CO2 with up to 30 wt.% ethanol and methanolshowing that, on a weight basis, methanol is a much better cosolvent although on a mole basis methanol is only slightly better.DME is the highest quality solvent for EC of the series of SCF solvents investigated. Although the EC+ DME system exhibitslower critical solution temperature behavior similar to the EC+ F22 system, EC dissolves in DME at lower temperatures andpressures compared with F22. Solution density data at the phase boundaries are reported for the EC+ SCF solutions. TheEC+ DME solutions exhibit the lowest densities which suggests that EC-DME cross interactions are very strong and likelydominated by hydrogen bonding.© 2003 Elsevier B.V. All rights reserved.

Keywords: Ethyl cellulose; Supercritical fluid solvents; Cosolvents; Solubility; Carbon dioxide

1. Introduction

Cellulose derivatives have attracted considerableattention in the pharmaceutical industry during thepast decade[1]. Among the many variants of cellu-lose, ethyl cellulose (EC) has garnered considerableattention since it can be used as a binder, dispers-ing agent, stabilizer, water conserving agent, anda slow-releasing agent in many kinds of medicinal

∗ Corresponding author. Tel.:+1-804-827-7031;fax: +1-804-828-3648.

E-mail address: mmchugh@vcu.edu (M.A. McHugh).

applications[1–3]. EC has also been used as a sub-strate film to act as an alignment layer for liquidcrystals[4]. Table 1shows the structure of the glu-cose repeat unit and the physical properties of the ECused in this study. The EC has a degree of substitu-tion of 2.5 which means that 16.7% of the ‘R’ groupsin the glucose unit shown inTable 1 are replacedwith hydrogen, 41.6% are replaced with ethyl groups,and the remaining 41.6% are replaced with ethoxylgroups. The EC repeat group can form inter- andintra-molecular hydrogen bonds which restricts themotion of the polymer backbone resulting in a ma-terial that is highly oriented and crystalline. EC does

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226 D. Li, M.A. McHugh / J. of Supercritical Fluids 28 (2004) 225–231

Table 1Select properties of EC reported by Scientific Polymer Products, Inc. and used in this study

Polymer Structure Mw(kg/mol)

Tglass

(◦C)Tmelt

(◦C)Mw/Mn Average degree

of substitution

Ethyl cellulose, R= 16.7% H,41.6% Ethoxyl, 41.6% Ethyl

180 43 165 4.0 2.5

Molecular weight is determined using poly(styrene) standards.

not dissolve in water, but it does dissolve in many or-ganic solvents, such as benzene, carbon tetrachloride,ethylene dichloride, methylene chloride, toluene, andxylene[1]. The goal of the present study is to deter-mine the solubility of EC in a variety of supercriticalfluid (SCF) solvents and cosolvents that may beconsidered replacement solvents for processing EC.

Over the past decades, SCF technology has showngreat promise in pharmaceutical and biological ma-terials processing[5,6] and SCF technology has beenconsidered for processing different forms of cellu-lose [7–9]. DiNoia et al. [8] report that celluloseacetate/butyrate (CAB) remains insoluble in neat su-percritical CO2 and in CO2 with ethanol or chlorodi-fluoromethane cosolvent. However, the authors of thiswork limited the operating conditions to a maximumof 85◦C and 1245 bar. Kiran and Pohler[9] report onthe solubility of cellulose derivatives in ethanol andacetone modified supercritical CO2. Kiran and Pohlershow that ethanol is a better cosolvent than acetone,that a single phase can be obtained at pressures as

Table 2Critical temperature (Tc) [12], pressure (Pc) [12], volume (Vc) [12], polarizability (�) [27], and dipole moment (�) [12] of the solventsand cosolvents used in this study

Solvent Tc (◦C) Pc (bar) Vc (cm3/mol) � (Å3) � (D)

Carbon dioxide 31.0 73.8 94.0 2.7 0.0Chlorodifluoromethane 96.2 49.7 165.0 4.5 1.4Difluoromethane 78.5 53.4 120.8 2.5 2.0Fluoroform 26.2 48.6 132.7 2.7 1.61,1-Difluoroethane 113.1 45.2 181.0 4.3 2.31-Chloro-1,1-difluoroethane 137.2 41.2 231.0 6.4 2.1Dimethyl ether 126.9 52.4 178.0 5.1 1.3Methanol 229.4 80.9 118.0 3.2 1.7Ethanol 240.8 63.0 167.0 5.1 1.7

CO2 has a quadrupole moment of−4.3× 10−26 erg1/2 cm5/2.

low as∼70 bar, but that 70 wt.% cosolvent is neededto obtain very low operating pressures.

In the present work, EC is the only cellulosederivative considered and only an EC concentrationof ∼1.0 wt.% is examined. The neat SCF solvents in-clude chlorodifluoromethane (F22); difluoromethane;1-chloro-1,1-difluoroethane; 1,1-difluoroethane; anddimethyl ether (DME). Data are also reported for ECin CO2 with ethanol, to extend the previously reportedwork of Kiran and Pohler[9], and with methanol tocompare the cosolvent strength of these two alcohols.Physical property data on the solvents and cosolventsare reported inTable 2. The fluorocarbon solventshave significant dipole moments, which should makethem reasonable solvents for EC, which is a polarpolymer. In preliminary tests, EC did not dissolve influoroform up to 200◦C and 2000 bar, and no furtherstudies with this solvent were performed. EC alsodoes not dissolve in neat CO2, which does not havea dipole moment because of structural symmetry, butdoes have a significant quadrupole moment due to the

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different electronegativities of carbon and oxygen. Thetwo alcohol cosolvents are expected to hydrogen bondto the repeat groups in EC as well as to self-associate.Hence, the cosolvency effect is expected to be de-pendent on temperature, concentration of polar repeatgroups in the EC, and concentration of cosolvent insolution. The strength of the interaction of a complexcan be up to an order of magnitude greater than thatof physical interactions associated with dispersionforces so the effect of these cosolvents is expected tobe significant[10,11]. DME has a dipole moment of1.3 Debye[12] and it is a proton acceptor (Br�nstedbase), that hydrogen bonds with proton donors suchas ethoxyl and hydroxyl groups[13]. However, DMEdoes not hydrogen bond to itself since it is not also aproton donor. The DME; 1-chloro-1,1-difluoroethane;and 1,1-difluoroethane results will be compared toprovide insight into the effect of the fluorine andchlorine groups on solubility since the polarizabilityand dipole moment of DME are similar to those forthese two fluorocarbons. Literature phase behaviordata exist for the CO2 + alcohol mixtures used inthis study. Reighard et al.[14] present a thoroughreview of CO2–methanol phase behavior and showthat, for methanol concentrations below 25 wt.%, asingle phase is maintained at pressures greater than∼55 bar at temperatures near 25◦C and at pressuresgreater than∼150 bar at temperatures near 100◦C.Likewise, Pohler and Kiran[15] show that similarpressures are needed to maintain a single phase forCO2 + ethanol mixtures with ethanol concentrationsup to 30 wt.% and temperatures from 30 to 120◦C. Aswill be subsequently presented, the pressures neededto maintain a single phase for binary CO2 + alcoholsolutions are lower than those needed to dissolve ECin these binary mixtures. The data presented in thisstudy provide a rationale for determining whether anSCF solvent can replace an organic liquid solvent forprocessing EC in coatings and drug applications.

2. Experimental

Described elsewhere is the apparatus and tech-niques used to obtain polymer cloud points[16,17]using the synthetic method and a high-pressure,variable-volume cell. EC is charged to the cell towithin ± 0.02 g and the entrapped air is removed from

the cell by flushing with low pressure nitrogen. If a liq-uid solvent is used, it is added to within± 0.02 g witha syringe and then the SCF solvent of interest is trans-ferred into the cell gravimetrically to within± 0.02 gusing a high-pressure bomb. The mixture in the cellis viewed with a borescope (Olympus Corporation,model F100-024-000-55) placed against a sapphirewindow secured at one end of the variable-volumecell. A stir bar activated by a magnet located belowthe cell mixes the contents of the cell. Cloud pointsare reproduced three times to within approximately± 10.0 bar, as measured with a Heise pressure gauge(model CM-105952, accurate to within± 2.8 bar).For this study the cloud point is the condition whenit is not possible to see the stir bar. The pressure in-terval between the slightest onset of solution hazinessto the reported cloud point is less than 30 bar forall of the solutions except for the CO2 + methanolsolutions where the pressure interval is less than 34bar. These large pressure intervals are not unexpectedsince EC has a molecular weight polydispersity of4.0 and the EC concentration is∼1.0 wt.%, whichmeans that the cloud points are dew-point type tran-sitions that are harder to identify since only a smallamount of material precipitates. The system temper-ature is held to within± 0.3◦C, as measured with atype K thermocouple (Omega Corporation) calibratedin-house using a silicone oil bath and a thermome-ter (Fisher Scientific, catalog #15-000C) calibratedagainst NIST-traceable standards.

Byun et al.[18] describe in detail the technique usedto measure solution densities knowing the amount ofmaterial loaded into the cell and the volume of the cellat a given pressure and temperature. The cell volumeis determined by detecting the location of the internalpiston with an LVDT coil (Lucas Schaevitz Co., model2000-HR) that fits around a high-pressure tube andtracks the magnetic tip of a steel rod connected tothe piston. The solution densities have an accumulatederror of± 1.5%[18].

3. Materials

EC (CAS 9004-57-3), whose properties are shownin Table 1, was purchased from Scientific PolymerProducts Co. Carbon dioxide (medical grade, 99.8wt.%) was purchased from Roberts Oxygen Co.

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Difluoromethane (99.7 wt.%), chlorodifluoromethane(98 wt.%), fluoroform (99 wt.%), 1,1-difluoroethane(98+ wt.%), 1-chloro-1,1-difluoroethane (98 wt.%),dimethyl ether (99+ wt.%), methanol (99.8+ wt.%),and ethanol (absolute) were purchased from AldrichChemical Co., Inc and used as received.Table 2showsthe physical properties of the solvents and cosolvents.

4. Results and discussion

Fig. 1shows the conditions needed to dissolve∼1.0wt.% EC in difluoromethane, 1,1-difluoroethane,and 1-chloro-1,1-difluoroethane. At temperaturesgreater than∼140◦C the locations of the cloud-pointcurves scale directly with solvent polarizability orsolvent polarizability per molar volume indicat-ing that dispersion interactions fix the location ofthese curves. As the temperature is reduced below140◦C, each cloud-point curve increases sharply inpressure suggesting that either polymer–polymer orsolvent–solvent polar interactions dominate the inter-change energy and induces the system to phase sepa-rate. Dipolar interactions scale as the dipole momentdivided by the molar volume to the one half power[19]. Hence, the EC polymer drops out of solutionprobably due to strong polymer–polymer polar inter-actions since the location of the cloud-point curves atthese ‘colder’ temperatures does not scale with solventdipole moment/(solvent molar volume)1/2. Also, ECis expected to form intra- and inter-molecular hydro-gen bonds, which are favored at lower temperatures.

Fig. 1. Experimental cloud-point curves for∼1.0 wt.%ethyl cellulose (EC) in difluoromethane, 1,1-difluoroethane, and1-chloro-1,1-difluoroethane. A single phase exists at conditionsabove and to the right of each of the curves in this figure.

Fig. 2. Comparison of the experimental cloud-point curves for∼1.0 wt.% ethyl cellulose (EC) in dimethyl ether (DME) andchlorodifluoromethane. A single phase exists at conditions to theleft of each curve. For reference, the pure component vapor pres-sure curve of DME is also shown in the figure[28].

Fig. 2 shows a comparison of the cloud-pointcurves of∼1.0 wt.% EC in chlorodifluoromethane(F22) and DME. Both of the cloud-point curves ex-hibit positive slopes which makes them lower criticalsolution temperature (LCST) curves. It is interestingthat EC remains dissolved in F22 to temperatures aslow as 40◦C and pressures of 30 bar or less while ECfalls out of 1-chloro-1,1-difluoroethane, a moleculewith a larger dipole moment and polarizability, attemperatures below 65◦C regardless of the pressure.It is conjectured that the lone hydrogen in F22 readilyforms a hydrogen bond with the EC repeat unit thatkeeps EC dissolved in solution at low temperatures.As noted earlier, EC did not dissolve in fluoroform,which also has a lone hydrogen available to form ahydrogen bond. Evidently, the hydrogen in fluoroformis not as ‘acidic’ as the hydrogen in F22, a trend alsopredicted from computational chemistry calculations[20]. Other reports have appeared in the literatureciting chlorodifluoromethane as a better supercriticalfluid solvent than fluoroform for polar polymers thathave a high degree of ‘basic’ character[16,21–24].

Note that the EC-DME cloud-point curve alsoshows LCST behavior and it is shifted to highertemperatures which means that EC is more readilydissolved in DME than in F22. The polarizability anddipole moment of DME are similar in value to thoseof F22. However, DME has a higher critical tempera-ture than F22, which suggests that DME has a highercohesive energy density than F22. Also, the oxygen

D. Li, M.A. McHugh / J. of Supercritical Fluids 28 (2004) 225–231 229

Fig. 3. Solution densities at the cloud-point for∼1.0 wt.% EC indifluoromethane, 1,1-difluoroethane, 1-chloro-1,1-difluoroethane,chlorodifluoromethane, and DME. A single phase exists at condi-tions above and to the right of each of the curves in this figure.

in DME is expected to form hydrogen bonds withhydroxyl hydrogens in EC.Fig. 3 shows the solutiondensities at the cloud point for EC in difluoromethane,1,1-difluoroethane, 1-chloro-1,1-difluoroethane, chlo-rodifluoromethane, and DME. Notice that theEC-DME densities are significantly lower than theother solution densities which further suggests thatEC-DME interactions must be very strong since theenergetics of a solution scale with the strength ofinteractions multiplied by the solution density[11].

As noted earlier EC does not dissolve in neat CO2.However,Fig. 4 shows that∼1.0 wt.% EC does dis-solve in CO2 with 14–30 wt.% ethanol cosolvent.

Fig. 4. Experimental cloud-point curves for the ethyl cellulose(EC)–CO2–ethanol system obtained in this study. EC concentra-tions are∼1.0 wt.% for 11.1, 14.4, 18.1, and 25.0 wt.% ethanoland ∼3.0 wt.% for 30.0 wt.% ethanol. The open circles for the30.0 wt.% ethanol are data of Kiran and Pohler[9] and the filledcircles are data obtained in the present study. A single phase existsat conditions above each of the curves in this figure.

Fig. 5. Experimental cloud-point curves for the ethyl cellulose(EC)–CO2–methanol system obtained in this study. EC concen-trations are∼1.0 wt.% in each mixture. A single phase exists atconditions above each of the curves in this figure.

As the concentration of ethanol increases from 11 to30 wt.%, on an EC-free basis, the pressures neededto solubilize EC are reduced by as much as 400 barat temperatures from 45 to 140◦C. There is excel-lent agreement between the data at 3.0 wt.% EC inCO2+30 wt.% ethanol obtained in the present study tothat of Kiran and Pohler[9]. Fig. 5shows the methanolcosolvent has a similar effect to ethanol on theEC–CO2 cloud-point curves. Both alcohol cosolventsincrease the density of the solution and they contributefavorable alcohol–EC hydrogen bonding and polarinteractions that promote the formation of a singlephase. The strength of alcohol–EC hydrogen bondinginteractions for both alcohols are close in value basedon spectroscopic and calorimetric studies[25,26].Figs. 6 and 7show that the ethanol solutions have

Fig. 6. Solution densities at the cloud-point for the ethyl cellulose(EC)–CO2–ethanol system obtained in this study at the concentra-tions of ethanol given in the figure. EC concentrations are∼1.0wt.% for 11.1, 14.4, 18.1, and 25.0 wt.% ethanol and∼3.0 wt.%for 30.0 wt.% ethanol.

230 D. Li, M.A. McHugh / J. of Supercritical Fluids 28 (2004) 225–231

Fig. 7. Solution densities at the cloud-point for the ethyl cellulose(EC)–CO2–methanol system obtained in this study at the concen-trations of methanol given in the figure.

higher mass densities at the cloud point than themethanol solutions, although the molar densities ofboth solutions are almost equal. Hence, from a ther-modynamic viewpoint, based on molar densities,methanol and ethanol are equivalent cosolvents, al-though from a process viewpoint, based on massdensities, methanol is more effective in lowering thepressures needed to obtain a single phase.

5. Conclusions

EC can dissolve in polar SCF solvents although hightemperatures and pressures may be needed to obtain asingle phase. If the SCF solvent can hydrogen bond tothe glucose repeat unit in EC, the dissolution temper-atures and pressures are lowered considerably. Hence,alcohols are the preferred cosolvents for dissolving ECat modest operating conditions. Unfortunately, CO2 issuch a poor SCF solvent for EC that copious amountsof methanol or ethanol are needed to dissolve EC atmodest operating conditions. In fact, CO2 should beconsidered more as an anti-solvent rather than as asolvent for EC.

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