Inverse Gas Chromatography Study on London Dispersive Surface

Article pubs.acs.org/jced

Inverse Gas Chromatography Study on London Dispersive Surface Free Energy and Electron Acceptor−Donor of Fluconazole Drug Praveen Kumar Basivi,†,§ Visweswara Rao Pasupuleti,‡ Ramanaiah Seella,† Madhusudana Reddy Tukiakula,† Subramanyam Reddy Kalluru,* and Soo-Jin Park*,§ †

Department of Chemistry, Sri Venkateswara University, Tirupati, 517 502, India Institute of Food Security and Sustainable Agriculture, Universiti Malaysia Kelantan, Kelantan, 17600, Malaysia § Department of Chemistry, Inha University, Incheon, 22212, South Korea ‡

ABSTRACT: The inverse gas chromatography study on the fluconazole drug surface was performed, and the net retention volumes, polar probes, and VN of nalkanes are determined at four temperatures over the range 318.15−333.15 K. The net retention values of n-alkanes were used to evaluate the London dispersive surface free energy γLS by three different methods, namely, the Donnet−Park, Dorris−Gray, and Schultz methods. The γLS values were found to increase from 318.15 to 323.15 K for all three methods and then decrease from 323.15 to 333.15 K. The γLS values were found to be slightly higher in the Schultz method when compared to the results of the Donnet−Park and Dorris−Gray methods. The specific free energy values ΔGSa and the specific enthalpy ΔHSa values have been calculated using the VN data of polar probes. The Guttmann Lewis acid−base parameters, Ka and Kb, were obtained using ΔHSa values and were found to be 0.217 and 1.518, respectively. The surface character (Kb/Ka) was found to be 7.0. The results revealed that the fluconazole powder surface contains relatively more basic sites than acidic sites and can combine strongly with acidic substrates. The surface energy and acid−base data of fluconazole can be used during formulation of the drug and to understand the drug release process.

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INTRODUCTION

In the current study, the surface thermodynamic properties of the fluconazole drug are repeated. The London dispersive surface free energy component, γLS , has been assessed by the Schultz7 et al., Donnet−Park,8 and Dorris−Gray9 methods. The Gibbs specific component of surface free energy ΔGSa obtained by the Schultz method is used to evaluate the Guttmann Lewis acid−base parameters. To the best of our knowledge, this is the first study to report the surface characterization of fluconazole using IGC. Theory of IGC. Net retention volumes VN have been analyzed by using the below mentioned equation

Inverse gas chromatography (IGC) is considered as one of the standard methods for the surface characterization of pharmaceutical powders. The Lewis acid−base parameters as well as the London dispersive component of the surface free energy of pharmaceutical drugs are usually determined using the IGC technique. Inverse gas chromatography can be used to measure the Lewis acid−base parameters and dispersive component of the surface free energy of pharmaceutical powders.1−3 The surface energy parameters are useful to find out batch-to-batch variation of pharmaceutical drugs. In addition to this, the surface energy parameters are also useful to define the humidity influence on the drug and also the differences during the synthesis of the drug including powdering of the drug. Fluconazole is used to avoid and treat different types of fungal and yeast infections. It functions by preventing the growth of particular types of fungi.4−6 The surface energetics of fluconazole powder influences its communication with the addition of solid or liquid during its formulation. The interfacial energy develops at the interface of two concise systems. This interfacial energy occurs because of the specific surface energies of both systems. The interfacial energy affects various factors including binding a film to a tablet, wet granulation, partition wetting and spreading the liquid on a solid surface, and suspension formation of a drug during processing. © XXXX American Chemical Society

⎛ P − Pw ⎞ VN = (t R − t0)FJ ⎜ o ⎟ ⎝ Po ⎠

(1)

The Donnet−Park method equation was used to measure the London dispersive surface free energy γLS , of fluconazole ⎛ (ΔG )2 ⎞ CH 2 ⎟ γsL = −⎜⎜ 2 2 ⎟ 4 N a ⎝ A CH2 γCH2 ⎠

(2)

where ΔGCH2 is the additional free adsorption energy of the methylene group CH2, equal to Received: February 14, 2017 Accepted: June 2, 2017

A

DOI: 10.1021/acs.jced.7b00169 J. Chem. Eng. Data XXXX, XXX, XXX−XXX

Journal of Chemical & Engineering Data ⎛ V [C H ]⎞ ΔGCH2 = −RTLn⎜⎜ n + 1 n + 1 2n + 4 ⎟⎟ ⎝ Vn[Cn ,H 2n + 2] ⎠

Article

Table 1. Physical Constants for Probes Used in IGC Experiments (3)

a(γdl )0.5 × 10−16

Here, a2CH2 is the surface of area of CH2, which has been assumed by Gray et al. as 6 Å2, and γCH2 is the surface free energy of a CH2 group; that is, γCH = 35.6 − 0.058(t − 20) 2

in mJ/m 2

solute

(4)

The London dispersive surface free energy of fluconazole was determined using the Dorris−Gray equation:

( ) ⎤⎥⎥

2

⎥ ⎥⎦

(5)

2

(6)

VN,n+1 is the net retention volume of n-alkanes with carbon n + 1 and VN,n is the net retention volumes of n-alkanes with carbon numbers n, aCH2 = 6 Å2 is the absorbed methylene group’s cross-sectional area and N is Avogadro’s number, T is column temperature, and R is gas constant. Alternatively, the London dispersive surface free energy is evaluated by using eqs 7 and 8 as proposed by Donnet−Park and Schultz et al., respectively, where F is carrier gas flow rate, Po is the atmospheric pressure, Pw is the saturated vapor pressure of water at ambient temperature, t0 is the retention time of methane, tR is the retention time of the probe solute, and J is the James and Martin pressure correction factor. As reported by Schultz, the London dispersive surface free energy γdS is related to the net retention volume as mentioned below: RT ln VN = 2Na(γld)0.5 (γSd)0.5 + K

DN

(nm )

(kJ/mol)

(kJ/mol)

0.515 0.570 0.630 0.690 0.750 0.425 0.470 0.315 0.440 0.450 0.480

10.5 6.3 16.4 22.7 2.1 6.3

71.4 80.6 0 0 84.4 71.8

hv

ao (×10−40)

(hv)1/2ao (×10−49)

probe

ev

C m2/v

C3/2 m2/v1/2

DN

AN*

n-hexane n-heptane n-octane n-nonane n-decane acetone diethyl ether trichloromethane tetrahydrofuran ethyl acetate

3.30 2.83 2.63

13.24 15.24 17.69

4.14 3.54 3.40 3.73 3.36

7.12 9.71 10.57 8.77 10.79

9.2 10.3 11.4 12.5 13.6 5.8 7.3 7.8 6.8 7.9

17.0 19.2 0 20.0 17.1

12.5 3.9 23.1 8.0 9.3

(10)

where VN(ref), the net retention volume, was established by the n-alkane reference line for the same polar solute, and VN is the net retention volume for the polar solute. For instance, the evaluation of ΔGSa graphically has been shown in Figures 1 and 2 for tetrahydrofuran (THF) and ethyl acetate at 318.15 K. By determining the ΔGSa values at disparate temperatures, it is desirable to compute the entropy of adsorption, ΔSSa , and specific components of the enthalpy of adsorption, ΔHSa , as reported by the following relation:

(7)

−

ΔGaS −ΔHaS = + ΔSaS T T

(11)

The ΔHSa values are used to determine the Lewis acidity parameter Ka, and the Lewis basicity parameter, Kb, as reported by the following relation: −ΔHas ⎛ DN ⎞ ⎟ + K = Ka⎜ b ⎝ AN* ⎠ AN*

(8)

The Gibbs free energy of adsorption consists of two constituents which are (i) the specific component,ΔGSa , and (ii) the dispersive component,ΔGda . Thus, ΔGa = ΔGad + ΔGaS

AN* 2

−ΔGaS = RT ln VN − RT ln VN(ref)

where K is the constant where it depends on the pressure of the gas as well as the pressure of the surface. γdl is the dispersive surface free energy of the solute, a is the cross-sectional area of the solute, and N is Avogadro’s number. If eq 2 is fitted into the n-alkane data, a linear plot can be plotted. From the slope of this particular linear plot, the London dispersive component of the surface free energy, γLS , can be calculated. The a(γdl )0.5 values for n-alkanes and for polar solutes are given in Table 1 and Table 2, respectively. The free energy of adsorption, ΔGa, is relevant to the net retention volume as follows: ΔGa = −RT ln VN + K

2.21 2.57 2.91 3.29 3.63 1.73 1.82 1.65 2.24 2.13 1.95

A

Table 2. Physical Constants for Probes Used in IGC Experiments

where γCH2 is the London dispersive surface free energy of the solid material and is determined at any specific temperature t (°C) using the below mentioned equation:

γCH = 35.6 − 0.058t

2 0.5

cm (mJ/cm )

n-hexane n-heptane n-octane n-nonane n-decane acetone diethyl ether dichloromethane trichloromethane tetrahydrofuran ethyl acetate

γdS

⎡ VN, n + 1 ⎢ RT ln VN,n 1 ⎢ γsd = 4γCH ⎢ N ·aCH2 2 ⎢⎣

2

(12)

where DN is Guttmann’s modified acceptor and AN* is donor numbers. The DN and AN* values of the polar solutes are given in Table 1 and Table 2, respectively.

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(9)

EXPERIMENTAL SECTION Analytical grade probe n-alkanes (C6−C10), acetone (AC), tetrahydrofuran (THF), ethyl acetate (EA), diethyl ether (DEE), dichloromethane (DCM), and trichloromethane (TCM) were purchased from S. D. Fine Chemicals Ltd. and

It is examined that only the dispersive interactions were represented by n-alkanes, and polar solutes represented by both dispersive and specific interactions. The ΔGSa for polar solutes can be calculated using the following relation: B

DOI: 10.1021/acs.jced.7b00169 J. Chem. Eng. Data XXXX, XXX, XXX−XXX

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K. A Hamilton syringe was used to inject 0.1 mL of each probe in triplicate, and the average in triplicate retention times was calculated for net retention volume VN.

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RESULTS AND DISCUSSION The net retention volumes VN of the n-alkanes and polar solutes measured on the GC column containing fluconazole as the stationary phase at the 318.15−333.15 K temperatures are tabulated in Table 3. The VN values are decreased with Table 3. Values of VN (cm3) for n-Alkanes and Polar Solutes on the Fluconazole Surface

Figure 1. RT ln VN versus a γld for n-alkanes and polar probes on the fluconazole surface at 318.15 K (Schultz method).

solute

318.15 K

323.15 K

328.15 K

333.15 K

n-hexane n-heptane n-octane n-nonane n-decane acetone diethyl ether dichloromethane trichloromethane tetrahydrofuran ethyl acetate

3.10 6.88 14.29 30.63 67.42 6.55 2.84 3.83 5.22 5.69 5.29

2.08 4.25 10.46 26.27 58.55 2.8 1.41 1.96 2.92 3.95 2.8

1.97 3.82 7.96 23.93 47.36 2.78 1.42 2.1 3.02 4.19 3.02

1.70 3.70 8.08 17.68 37.27 2.03 1.31 1.86 2.64 3.70 2.42

increasing temperature. The graph between RT ln VN, versus (hv)1/2ao, and a γld were found to be linear for n-alkanes at the four different temperatures at both the methods. The values are calculated using eq 8 and 9. The variation of RT ln VN, (hv)1/2ao, anda γld is shown in Figures 1 and 2. As reported by the Donnet−Park, Schultz, and Dorris−Gray methods, the values of the London dispersive surface free energy component γLS are calculated from the slopes of the RT ln VN, (hv)1/2ao, and

a γld plots. The γLS values are calculated using eqs 2−7. The values of γLS calculated using the three methods are shown in Table 4. The γLS values decreased with temperature in all the Table 4. London Dispersive Surface Free Energy, γLS (mJ/ m2) of Fluconazole

Figure 2. RT ln VN versus (hv)1/2ao for n-alkanes and polar probes for the fluconazole surface at 318.15 K (Donnet−Park method).

Merck. Fluconazole drug in powder form was purchased from Sigma-Aldrich, USA. The fluconazole was directly used for the formation of the packed column. A stainless steel column with the length of 50 cm and internal diameter of 3 mm was washed with methanol and acetone, and then dried in an oven to remove surface moisture. The weight of the column was recorded before and after packing with fluconazole. The fluconazole weight in the column was found to be 1.0370 g. The packing was performed under vacuum pressure. Once the column is packed, glass wool was used at both ends of the column as plugging material and conditioned with nitrogen flow for 12 h. The flow rate of nitrogen is 5.84 mL/mins. The out flow rate of nitrogen was calculated by using soap bubble meter. The details of the dual column NUCON 5765 gas chromatograph and the measurement of the retention data of nalkanes and polar probes have been described earlier.10 The instrument was rigged with a flame ionization detector. The retention times were measured at constant oven temperatures at intervals of 5 K over the temperature range 318.15−333.15

T (K)

γLS (Schultz)

γLS (Dorris−Gray)

γLS (Donnet−Park)

318.15 323.15 328.15 333.15

22.28 28.03 27.25 25.00

18.80 23.93 23.00 21.09

13.07 19.10 17.48 14.75

three methods. Compared to the Donnet−Park and Dorris− Gray methods, the γLS values are slightly higher using the Schultz method. The γLS values increase from 318.15 to 323.15 K for all the three methods, and then decrease from 323.15 to 333.15 K for all three methods. In the fluconazole structure there are −F and −OH groups. The intramolecular hydrogen bonding and fluorine−chlorine repulsion occurred between probes and drug material. In the range 318.15−323.15 K the γLS value indicates that the structural changes on the surface of the solid material allowed for the penetration of the probe molecules. The temperature gradient of γLS is negative which might be ascribed to escalation in the distance of accession between the fluconazole molecules with the elevation in the temperature. In the London expression, the dispersive energy is C

DOI: 10.1021/acs.jced.7b00169 J. Chem. Eng. Data XXXX, XXX, XXX−XXX

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inversely proportional to the sixth power of the distance of separation between the molecules. Hence, the dispersive energy decreases with the escalation of temperature as well as the distance of dissolution between molecules increases with the temperature elevation.7,11,12 The variations in the results clearly show that, in all the three methods used in this study such as (i) Donnet−Park, (ii) Dorris−Gray, and (iii) Schultz method, the London dispersive surface energy values were found to increase and then decrease with increasing temperature. This discrepancy may be attributed to the values of the dispersive surface tensions of the liquid probes, γSL. Therefore, the Schultz method is potentially significant at elevated temperatures for the estimation of the London dispersive surface energy, γLS than the other methods used in this study which are Donnet−Park and Dorris−Gray methods. However, all the methods are applicable at ambient temperatures, unless the temperature dependence of γLS is known. The similar scenario has been reported and warranted by the other researchers previously.7,11−13 The ΔGSa values, analyzed by using eq 10, are shown in Table 5, and the variation of ΔGSa with T is not linear. Generally, the

Figure 3. Variation of −ΔGSa /T with 1/T for polar solutes on the fluconazole surface.

Table 6. Specific Components of the Enthalpy of Adsorption, ΔHSa , Entropy of Adsorption, ΔSSa , and the Correlation Coefficient, r, for Polar Probes on Fluconazole

Table 5. Specific Component of the Surface Free Energy −ΔGSa (kJ/mol) for Polar Solutes on Fluconazole solute

318.15 K

323.15 K

328.15 K

333.15 K

AC DEE DCM TCM THF EA

3.31 1.95 3.71 1.18 2.04 2.88

4.04 1.60 3.58 1.67 2.31 2.63

4.18 0.78 3.92 1.22 2.78 3.04

3.46 1.41 3.61 1.03 2.63 2.36

solute

ΔHSa (kJ/mol)

AC DEE DCM TCM THF EA

31.96 31.92 17.35 33.83 20.98 23.74

± ± ± ± ± ±

3.17 4.54 4.52 4.69 1.69 4.29

ΔSSa (kJ/mol K)

r

± ± ± ± ± ±

0.995 0.999 0.938 0.981 0.994 0.996

0.086 0.091 0.041 0.099 0.055 0.066

0.01 0.01 0.01 0.01 0.01 0.01

numerical values of ΔGSa are based on the strength of the acid− base communication between the adsorbent and polar probe. Additionally, the ΔGSa values also depend on the regular area of adsorption of the probe on the drug material. The Gibbs surface energy of adsorption becomes more negative with increasing temperature. ΔGSa values were found to decrease with an increase of temperature in the range 318.15−333.15 K. The ΔGSa values were found to decrease in the following order. DCM < AC < EA < THF < DEE < TCM S

A linear fit was obtained between −ΔGa and 1 , which T T provides the ΔHSa and ΔSSa values from the slope as well as from S

the intercept. The deviation of −ΔGa with 1 is constructed to be T T linear in Figure 3, and hence, a statistical approach was used to evaluate the ΔHSa and ΔSSa values. The ΔHSa and ΔSSa values along with correlation coefficient r are tabulated in Table 6. Furthermore, the ΔHSa values are used in eqs 11 and 12 to estimate the Lewis acid−base parameters for the fluconazole s drug surface. The variation of −ΔHa with DN is shown in Figure AN * AN * 4, and was found to be linear with r = 0.989. The Ka and Kb values were calculated using linear plot’s slope and intercepts. The values of Ka, Kb, and the surface character, S = (Kb/Ka), were determined to be 0.217, 1.518, and 6.99, appropriately. The Ka and Kb values were associated with the quality and nature (acidic or basic) of the sites of fluconazole surface. Overall features of the fluconazole surface were represented by S values. If the S value is found to be higher than 1, then the

Figure 4. Plot of −ΔHSa /AN* versus DN/AN* on the surface of fluconazole.

overall surface character is considered to be basic, if less than 1, the surface is considered as acidic. Thus, in the present study the fluconazole surface, and its overall character is found to be basic. The results revealed that the fluconazole drug surface contains more basic sites than acidic sites and hence can closely associate in acidic media.

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CONCLUSION The net retention VN values of polar solutes and n-alkanes on a fluconazole powder surface were determined at four temperatures over the range 318.15−333.15 K by IGC. The γLS values D

DOI: 10.1021/acs.jced.7b00169 J. Chem. Eng. Data XXXX, XXX, XXX−XXX

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(11) Santos, J.M.R.C.A.; Guthrie, J. T. Study of a core-shell type impact modifier by inverse gas chromatography. Journal of Chromatogr A 2005, 1070, 147−154. (12) Al-Ghamdi, A.; Al-Saigh, Z. Y. Surface and thermodynamic characterization of conducting polymers by inverse gas chromatography. Journal of Chromatogr A 2002, 969, 229−243. (13) Kondor, A.; Quellet, C.; Dallos, D. Surface characterization of standard cotton fibres and determination of adsorption isotherms of fragrances by IGC. Surf. Interface Anal. 2015, 47, 1040−1050.

increased from 318.15 to 323.15 K, and then decreased with an increase in the temperature from 323.15 to 333.15 K. The γLS value was maximum at 323.15 K and it was found to be 28.03 mJ/m2. Most of the work here discussed the London dispersive surface energy γLS and the rest discussed the Gibbs free energy, surface character, and the Lewis acid−base parameters on fluconazole. The Lewis acidity parameter Ka was found to be 0.217 and Lewis basicity parameter Kb was found to be 1.518. The results revealed that the fluconazole surface contains more basic sites and can interact strongly with an acidic environment.

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AUTHOR INFORMATION

Corresponding Authors

*E-mail: [email protected]. *E-mail: [email protected]. ORCID

Praveen Kumar Basivi: 0000-0002-8214-9532 Visweswara Rao Pasupuleti: 0000-0002-4454-3408 Soo-Jin Park: 0000-0002-6350-6135 Funding

The Leading Human Resource Training Program of Regional Neo industry through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (Grant No. NRF-2016H1D5A1909732) and the Industrial Strategic Technology Development Program (10050953) funded by the Ministry of Trade, Industry & Energy (MI, Korea) are acknowledged for the support. Notes

The authors declare no competing financial interest.

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REFERENCES

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DOI: 10.1021/acs.jced.7b00169 J. Chem. Eng. Data XXXX, XXX, XXX−XXX