TY - JOUR

T1 - The influence of heat capacity assumptions on the estimation of solubility parameters from solubility data

AU - Neau, Steven H.

AU - Flynn, Gordon L.

AU - Yalkowsky, Samuel H.

N1 - Funding Information:
The authors would like to acknowledge the assistance of Steven Krawczyk and Eric Meade in the synthesis of the pentyl ester. S.H.N. was supported by an NIH Training Grant in Pharmacological Sciences, Grant GM 07767, H. Helfman Pharmacy Student Aid and Parke Davis/Warner Lambert.

PY - 1989/2/1

Y1 - 1989/2/1

N2 - Regular solution theory indicates that solubility parameters of crystalline organic compounds can be estimated from solubilities in London solvents. The equation for this purpose is: IN X2 - ΔHf RTf (Tf-T) T + ΔCp R (Tf - T) T - ln Tf T - V2θ21 RT (δ1 - δ2)2 where X2 is the mole fraction solubility of a compound in a solvent with a solubility parameter of δ1. With the exception of ΔCp, all parameters in the equation necessary to estimate the solute parameter, δ2, can either be suitably approximated or readily determined experimentally. In order to use the equation, simplifying assumptions have been made concerning ΔCp, namely: ΔCp = 0 or ΔCp = ΔSf, the entropy of fusion. In the present work, we have considered the extent to which these assumptions influence the magnitude of solubility parameters estimated from solubilities in n-hexane, n-heptane, n-dodecane, cyclohexane, carbon tetrachloride, toluene and benzene. Using n-alkyl p-aminobenzoates as test compounds, it is shown that solubility-based solubility parameters are relatively insensitive to the form of the equation used to calculate δ2. Specifically, solubility parameter estimations based on the two simplifying assumptions differ by no more than 0.2 (cal/ml) 1 2, an increment of the order of the presumed inherent error of estimation.

AB - Regular solution theory indicates that solubility parameters of crystalline organic compounds can be estimated from solubilities in London solvents. The equation for this purpose is: IN X2 - ΔHf RTf (Tf-T) T + ΔCp R (Tf - T) T - ln Tf T - V2θ21 RT (δ1 - δ2)2 where X2 is the mole fraction solubility of a compound in a solvent with a solubility parameter of δ1. With the exception of ΔCp, all parameters in the equation necessary to estimate the solute parameter, δ2, can either be suitably approximated or readily determined experimentally. In order to use the equation, simplifying assumptions have been made concerning ΔCp, namely: ΔCp = 0 or ΔCp = ΔSf, the entropy of fusion. In the present work, we have considered the extent to which these assumptions influence the magnitude of solubility parameters estimated from solubilities in n-hexane, n-heptane, n-dodecane, cyclohexane, carbon tetrachloride, toluene and benzene. Using n-alkyl p-aminobenzoates as test compounds, it is shown that solubility-based solubility parameters are relatively insensitive to the form of the equation used to calculate δ2. Specifically, solubility parameter estimations based on the two simplifying assumptions differ by no more than 0.2 (cal/ml) 1 2, an increment of the order of the presumed inherent error of estimation.

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U2 - 10.1016/0378-5173(89)90346-3

DO - 10.1016/0378-5173(89)90346-3

M3 - Article

AN - SCOPUS:0024502655

SN - 0378-5173

VL - 49

SP - 223

EP - 229

JO - International Journal of Pharmaceutics

JF - International Journal of Pharmaceutics

IS - 3

ER -