Solubility of Drugs

In pharmaceutical science, a solution is formed when a solute (such as a drug) is dissolved in a solvent (like water). The solubility of a substance is defined as the maximum amount of solute particles that can be dissolved in a given volume of solvent under specific conditions.

Solubility Expressions

Solubility is often described using the following terms:

1. Very soluble: Less than 1 part solvent needed

2. Freely soluble: 1-10 parts

3. Soluble: 10-30 parts

4. Sparingly soluble: 30-100 parts

5. Slightly soluble: 100-1000 parts

6. Very slightly soluble: 1000-10000 parts

7. Practically insoluble or Insoluble: More than 10,000 parts

1. Saturated Solution: Contains the maximum amount of solute that can be dissolved at a given temperature under normal conditions.

2. Unsaturated Solution: Can easily dissolve more solute.

3. Supersaturated Solution: Contains more dissolved solute than a saturated solution, often achieved by heating and then cooling the solution.

The process of dissolution involves three main steps:

1. Detachment of solute particles from the bulk

2. Creation of a cavity in the solvent

3. Insertion of detached solute particles into the solvent

Different types of solvents interact with solutes in various ways:

• Polar Solvents: Interact through hydrogen bonding and dipole-dipole interactions

• Non-polar Solvents: Dissolve non-polar solutes through induced dipole interactions

• Semi-polar Solvents: Dissolve semi-polar solutes through dipole moments

Solvation describes the interaction of solvent molecules with dissolved solute molecules. In aqueous solutions, this process is called hydration. When ionic particles undergo solvation, they may dissociate into ions, a process known as association.

Types of solvation:

1. Fully solvated

2. Solvent shared

3. Contact ion pairs

Several factors can influence the solubility of a substance:

1. Nature of the solute and solvent

2. Surface area of the solute

3. Temperature

   • For solid in liquid: Generally increases with temperature

   • For gas in liquid: Generally decreases with temperature

4. Pressure (primarily for gases)

Binary solutions are formed when two liquids are mixed. They can be classified as:

1. Completely miscible (e.g., ethanol and water)

2. Partially miscible (e.g., phenol and water)

3. Immiscible (e.g., oil and water)

Critical Solution Temperature (CST)

In partially miscible solutions, the CST is the temperature at which two liquids become completely miscible.

• Ideal Solutions: Follow all solution laws perfectly (e.g., Raoult's law, Henry's law)

• Non-ideal Solutions: Deviate from solution laws

Laws Governing Ideal Solutions

1. Henry's law

2. Raoult's law

3. Dalton's law

4. Charles' law

Diffusion is the process by which molecules move from an area of high concentration to an area of low concentration. This principle is crucial in understanding drug absorption and distribution in the body.

Fick's Laws of Diffusion

1. First Law: J = -D(dc/dx)

   • J: flux of a component (rate of diffusion)

   • D: Diffusion constant

   • dc/dx: Concentration gradient

2. Second Law: dc/dt = D(d²c/dx²)

   • Describes how concentration changes with time in a particular region

Applications in pharmaceutical science:

1. Release of drugs from dosage forms

2. Dissolution

3. Prediction of absorption

The distribution coefficient is used to determine the nature of a solute (hydrophilic or lipophilic). It's calculated as:

P = Xo / Xw

Where:

• Xo: Drug dissolved in organic phase

• Xw: Drug dissolved in water phase

If P > 1, the drug is lipophilic; if P < 1, the drug is hydrophilic.

Separation Method for Determining Partition Coefficient

1. Mix the drug with equal volumes of organic solvent and water in a separating funnel

2. Shake for 15 minutes

3. Allow phases to separate

4. Take samples from each phase

5. Determine drug concentration using UV spectroscopy

6. Calculate the partition coefficient

Understanding solubility and related concepts is fundamental in pharmaceutical science. It helps in predicting drug behavior, designing dosage forms, and optimizing drug delivery systems. The principles of solubility, diffusion, and partition coefficient play crucial roles in drug formulation, absorption, distribution, and overall efficacy.