Ideal Solubility parameters Physical Pharmaceutics

Ideal Solubility parameters Physical Pharmaceutics

Regular solution theory characterizes non-polar solvents in terms of solubility parameter, 

δ1, which is defined as

Where ∆U is the molar energy and ∆H is the molar heat of vaporization of the solvent.        

The ∆H is determined by calorimetry at temperatures below the boiling point at constant volume and V is the molar volume of the solvent. The solubility parameter is thus a measure of the intermolecular forces within the solvent and gives us information on the ability of the liquid to act as a solvent. The ratio ∆U/V is the liquid’s cohesive energy density, a measure of the attraction of a molecule from its own liquid, which is the energy required to remove it from the liquid and is equal to the energy of vaporization per unit volume. As cavities have to be formed in a solvent by separating other solvent molecules to accommodate solute molecules the solubility parameter δ1 enables predictions of solubility to be made in a semi-quantitative manner, especially in relation to the solubility parameter of the solute, δ2. By itself, the solubility parameter can explain the behavior of only a relatively small group of solvents  –  those with little or no polarity and those unable to participate in hydrogen bonding interactions.  The difference between the solubility parameters expressed as (δ1-δ2) will give an indication of solubility relationships. For solid solutes, a hypothetical value of δ2 can be calculated from (U/V)1/2, where U is the lattice energy of the crystal. In a study of the solubility of ion pairs in organic solvents, it has been found that the logarithm of the solubility (log S) correlates well with (δ12)2.

Units of Solubility Parameter:

Conventional Unit : (Cal/cm3)1/2  or  Cal ½  cm -3/2

S. I. Unit:  J1/2 m -3/2 

Applications of Solubility Parameter:

  1. Selection of Solvent
  2. Preparation of polarity scale 
  3. Covalence power detection
  4. Chemical kinetics determination 
  5. Determination of mechanism involved in drug
  6. Structural activity relationship (SAR) 
  7. Drug transport through model membrane

Advantages of Regular Solution Theory

  1. To predict access for energy mixing 

Limitations for Regular Solution Theory

Not able to predict thermodynamic property 

  1. Heat of solution 
  2. Volume after mixing

Ideal Solubility parameters video lecture

Video Credits:

Dr. Govind Kailash Lohiya
Gurunanak College of Pharmacy, Nagpur
Physical Pharmaceutics I (BP302T)
Unit 1 solubility of drugs Physical Pharmaceutics Ideal Solubility parameters