1 Gram Thermadsramis 71 (2014) 231-255 Contents lists available at ScienceDirect J. Chem. Thermodynamics Pan Journal homepage: www.elsevier.com/locate/jet ELSEVIER Application of the NRTL method to correlate solubility of diosgenin Meow Fei-xiong Chen, Zhen-li Qi, Lu Feng, Jun-yan Miao, Bao-zeng Ren * Cee of chemical Engineering and Energy, Zhengzhou Univesity 450001 China ARTICLE INFO ABSTRACT ‘Accepted 17 December 2015, - Using the synthetic method, the solubility of diosgenin in 1chexanol and T-heptanol was measured at {temperatures Irom 300 K to 329K by laser monitoring observation technique at atmospheric pressure ‘The solubility data were correlated by semi-empirical equations, such se the Apelbiat equation, ih model and the ideal model, which agreed well with experimental results. The fusion enthalpy and the melting point determined by diferenia scanning calorimeter (DSC). are - 24054 2] mol and 207.08 °C for Aiosgenin. With collection of over 14 solvents from different references, the NRTL thermodynamic mode! oa {sone ofthe activity coefient models wasted to concasand pred the solubility of osgenin The Dresaein Selby aula frail solvents showed god agreement withthe experimental rests within the (Stl ei eqirio temperature range stated, Addonaly, the soabity of cosgenin in 1 solvent sls investigated or SVTe.15 the cess of whic indkated that soil of dosgenin neaanas ends to netesse Organic rlvents ‘uth increasing alkanol chain length feom methanol to -heptanol and n-alkanols presented higher sol bility than heterogeneous alcohols for diosgenin, suchas L-butanol > isobutyl alobol > tert-butanol and 1-propanol » isopropanol. It also shows that solubility of osgenin decreases withthe increasing polarity of solvents. ts corresponding (slid + igud) equiibeum data wil provide essential support fr indstial esign and frther detailed theoretical studies ‘crown Copy ight © 2013 Published by Elsevier Lr. All ight reserved 1. Introduction Crystallisation is the preferred method of purification in the pharmaceutical industry for both the final drug substance and the isolated intermediates in the synthesis (||, Diosgenin (CAS No. 512-048) is a steroid sapogenin and the precursor for the semi-synthesis of progesterone, which is also used for the com- mercial synthesis of cortisone, pregnenolone, progesterone, and other steroid products [2 Previously, Chen et al [3,4] have determined the solubility of diosgenin in different solvents, the findings of which have been re- ported. However, all the solubility data were correlated by semi- empirical equations. Although those results showed that solubility data agreed well with those equations, semi-empirical equations were not based on any theory and cannot be used to predict solu- bility to some degree. In this study, therefore, we investigated the NRTL model to correlate experimental data of diosgenin in 14 sol- vents and analyzed solubility rule of diosgenin in different sol- vents, so that this work can provide a valuable prediction in diosgenin solubilities. TF Coreponding autor maladies: rena ceueds.co (Bea Ren 2. Experimental 2.1, Material 1-Hexanol and 1-heptanol were purchased from Sinopharm ‘Chemical Reagent Co,, Ltd with mass fraction purty of 0.985 and (0995, respectively, All the solvents used in the experiments were of AR grade. Diosgenin crystals (mass fraction purity > 0.99) used Jn this experiments was purchased from Zhengzhou Lion Biotech- nology Co. Ltd ‘The apparatus and method used to determined solubility of diosgenin are the same as in our former work [4 22. Thermal analysis ‘The DSC measurements were carried out with a differential scanning calorimeter DSC1 (METTLER TOLEDO, Swiss) to deter- ‘mine the fusion enthalpies and the melting temperatures for dios- genin, About 2.5 mg diosgenin powder was put in a closed DSC pan, For each DSC experiment, an empty DSC pan Was used as a blank reference. The sample was scanned from 0°C to 240°C at 2 heating rate of 10°C. min” 0021-8514)5 see oat marer Crown Copyight © 2015 Published by Hse Le Al sighs reserved pedaa Fox Che el Chen Terman 712014) 231-255 Sty of dose in ean and tao Tie 1 To) ToD waa HDD Wea nD 32795 18077 007 18268 106 11978 085 ‘oon toe 6 on yormse i 2408 2a 100AAD 1420 1498: 1430 tosmiso ane 20 2353, {2)2 (uh, cape ae the eseaton day sh ode, Ape equaton and the el mode Free of equals ()-} or seein ‘eas -Bioa?__snnyo___s7s8__oanas__ ona __assa_—_ovoni___su008 yous ama 3, Thermodynamic models In) =A+8 + cin) @) 3.1 The semi-empirical equations xy (2 The relationship between mote fraction slubiliy and tempera tn 1+“) — aah) 8 ture is generally modelled, using the ideal model [4], the Apelblat equation [5] and the if model (6,7). Those models mentioned above are all semi-empirical equations, of which the detailed equa- tions are shown as follows (equations (1)-(3)) & ast Ing) a Here A, B are the parameters of equation (1)and A, B, C are the parameters of equation (2). Additionally, equation (2) is derived by Buchowski etal 6.7) where 2 and h are the equation parameters, ‘which are either adjusted tothe solubility data or estimated ina dif- erent way.Fox chen ea hem Thermadynamic 71 (2014) 231-235 bs rameters of NETL model eressed based on experimental seublty daa Gat) ten —en)_ © Methanol misibs4 2676662 09965 O18 287 Ethanol Neos 27889 9868 186790, erage 324558 (3) AAD and RMD are the average absolute deviation and the reotsmean square xis the experimental mole fraction of diosgenin in different sol- vents and Ts the equilibrium temperature. T, is the melting tem- perature of diosgenin, Generally, an empirical formula can be applied to correlate the solubility of diosgenin within the experimental temperature range. As references report (2.4), those equations produce good agree- ‘ment with experimental results, according to the parameters of ‘AAD and R?. ‘The ADD is the relative error of which is defined as follows: tea ADD = 4 ois ois 006 rk Xan! = Peon 4 o-ealeol © Methanol ‘1B spat X_ropanol + Herat Caleta FIGURE 1.1. Expecimental values and computed results coutelted by the NETL ode or the slubity dara ef seen oon rk 5 Replace Assicater {Sebuiyl alcohol TEBE + Sac 100A 0 alas ate ans aE aS Eo Experimental daa Banal ia also + Tertlaal | 1Fetoo FIGURE 2. Relative deviations Between the experimental and calculated data asa function of experimental slit The average absolute deviation (AAD) is given as follows: where m is the number of experimental points; x and x(cal) are the experimental and calculated mole fraction of solubility, respectively,ae x Chen eta} hem Thermotynamics 7 (2014) 231-235 slic length FIGURE 5 Slubty of dosgenin a diferent akan! cha length at T= 308.15 (sped 85 so-eey aleabe 3.2. NRTL model The NATL (Non Random Two Liquid) model was described in detail forthe first time by Renon and Prausnitz [3] who showed its application to a wide variety of mixtures for calculation of (vapour + liquid} and (liquid + liquid) equilibrium. This model is based on the molecular local composition concept which is expressed as follows a Mtn Ing, = SG ” DhareGe ey) Ga epee) = EB, ‘where 9 is the number of components; x represents the mole frac tion; Ris the gas constant; Tis the equilibrium temperature; is the activity coefficient of the i component; Gj is a dimensionless interaction parameter depending on the energy interaction param- eter gj and the non-randomness factor (1), For binary systems, the [NRTL model can be simplified and described as follows |) ty =Bn=Ba) En ~fu) a = EaaBe) ,,, Ba Gin = exp(-anatia), Ga = exp(—aarfay), 21 ~ ot = 03. ‘The binary parameters (gi2fz2) and (1-81) ate regressed based ‘on experimental data of solubility. The NKTL model contains three parameters, but reduction of experimental data fora large number of binary systems indicates that a; varies from about 0.20 to 047 When expetimental data ate scarce the Value of 2; can often beset aubitrarily: a typical choice is 62) ~ 03. ‘Shown in equation (8), a knowledge of the activity coeficient which can express the nos+ideal behaviour of liquid mixtures is «essential before regression of binary parameters In order to calt- late the activity coefficient, a universal equation for (Solid iquid) 1-heptanol > I-hexanol > 1-pentanol > 1-butanol > 1-propanol > ethanol > methanol. Moreover, as 1-butanol> isobutyl alcohol> tert-butanol and 1-propanol> isopropanol shows in gure 4, n-alkanols show greater solubility than heterogeneous alcohols. For other solvents, there are in the sequence: acetic ether > propyl acetate > acetone, Overall, chose results indicate that solubility of diosgenin increases with the decreasing. solvent polarity. 5. Conclusions ‘The solubility of diosgenin in 1-hexanol and 1-heptanol within ‘temperature range 300K to 329K was measured in this work, ‘Additionally, the diosgenin solubility in over 14 solvents were col- lected in this research, There is consistency that raising the tem- perature increases the solubility of diosgenin in these different solvents, Comparing, the solubility in 14 solvents at T= 308 K indicates that solubility of diosgenin decreases with the increasing, polarity ofthe tested solvents. The solubility of diosgenin was the highest in iso-octyl alcohol in all solvents studied. Methanol showed the lowest solubility among all solvents studied. In addi tion, the temperature dependence of diosgenin solubility in different solvents can be well-correlated by semi-empirical ther- ‘modynamic models such as the 2h model, thte Apelblat equation and the ideal equation, Particularly, with binary interaction param- eters, NRTL thermodynamic models can satisfactorily correlate the solubility of diosgenin in different solvents over the experimental temperature range studied, which could be used to correlate the solubility data of diosgenin in industrial production, Appendix A. Supplementary data Supplementary data associated with this article can be found, in the online version, at hitp://dx-dot org/ 10.1016) jet. 2013.12.020. References Cher, Res. 45 (2005) 4816-4826, a Si China er. Chem In} chau-chyun Chen, ras eter A In [a] Wesheng Tan, cial Xu, Ling Chen, Chute (oot raza DL ete Ge Mg a Ch ta hes Teme 50 Ual Feisiong hea, Mingri Zhao, Haozeng Ken. etal | Chem, Therm. 47 [5] A Apel E Manzucola, Cher, Theemadyn. 31 (1999) 65-9 {el fis Buchowsie Phd Phase Eq 25 (1980) 292.278, [D1 H Buchowns, A Keaersk § Pitre} Phyr Chem 8 (1980) 975-979, [a] enon JM Prasat AIRE | 141968) 35-44 [a] race © Pong John We. Prausnte Jona P- OCennel 10) Kw Stanley, Pave Equi in Cherical Engineering, Bterwarth New York 1985 [11] U Doma, MK Koslow, chem. Eng. Dat 4 (2003) 557-86 1nd] ening Chea, Fu Lu Feng et al, fuss] Pays. chem A 87 (2013) 1611- Properties of cases, ICT 13-593