Solutions

Disperse systems are composed of two phases:

a. Dispersed (Internal) Phase

  • Can be molecules, particles, or droplets.

b. Continuous (External) Phase

  • Surrounds the internal phase.

2. Classification of Dispersed Systems

Type

Particle Size

Example/Notes

Solutions

< 1 nm (molecular)

Week 10

Colloidal Dispersions

0.001 to 0.5 µm

Includes surfactant micelles

Coarse Dispersions

10 to 50 µm

Week 11: Pharmaceutical suspensions

Intermediate Range

0.1 to 10 µm

Many pharmaceutical formulations fall here

Emulsions

-

Week 12

Aerosols

-

-

3. Pharmaceutical Solutions

a. Definition

  • Homogeneous molecular mixture of solute dissolved in a solvent.

  • Solutes and solvents may be solid, liquid, or gas.

  • Optically clear.

4. Solvent Systems

a. Aqueous Solvents

  • Water is most common.

    • Advantages: low cost, non-toxic

    • Disadvantage: poor solubility for many drugs

  • Types of Water:

    • Potable Water: Boiled and cooled; non-sterile uses

    • Purified Water: Distillation, ion-exchange, or reverse osmosis (non-parenteral)

    • Water for Injection (WFI): Pyrogen-free (for parenterals)

  • Co-solvents (to improve solubility):

    • Examples: PEG, ethanol, glycerol

b. Non-Aqueous Solvents

  • Used when drug is unstable or insoluble in water.

  • Examples: Ethanol, PEG, fixed oils, DMSO, ethyl ether

  • Limitations: toxicity, irritancy, route restrictions (e.g. IM or topical only)

5. Drug & Excipient Properties

a. Drugs

  • Can be small molecule or biotherapeutic

  • Solubility influenced by:

    • Molecular structure, crystal form, particle size

    • pKa & medium pH

b. Excipients

  • Examples: Sucrose (small), HPMC (large)

  • Functions:

    • Enhance stability, bioavailability, acceptability

    • Aid manufacturing and product identification

  • Requirements:

    • Non-toxic, non-irritant

    • Route-compatible

    • Stable throughout shelf-life

6. Classification of Solutions by Solvent System

Type

Examples

Aqueous

Syrups

Non-Aqueous

Elixirs, spirits, tinctures

7. Routes of Administration

Route

Examples

Oral

Syrups, elixirs, drops

Mouth/Throat

Gargles, mouthwashes, throat sprays

Body Cavities

Nasal sprays, ear drops, enemas

Body Surface

Lotions

Parenteral

IV, SC, IM (must be sterile, pyrogen-free)

8. Requirements by Route

Route

Requirements

Parenteral/Ocular

Sterile, isotonic, physiological pH

Oral

Palatable, isotonic if large volumes used

Multi-dose

Often contain preservatives

9. Solution Stability

  • Must maintain:

    • Physical, chemical, microbial, therapeutic & toxicological stability

  • Factors affecting stability:

    • Temperature, pH, UV, catalysts

  • Common degradation reactions:

    • Hydrolysis, oxidation, reduction, decarboxylation, epimerization

  • Strategies:

    • pH optimization

    • Protect from light (opaque containers)

    • Antioxidants (e.g. purge O₂ with N₂)

    • Preservatives for microbial protection

10. Solubility Enhancement Techniques

Technique

Description/Examples

pH Adjustment

Based on drug’s pKa; use Henderson–Hasselbalch

Co-solvents

Glycerol, ethanol, propylene glycol

Cyclodextrin Complexation

Non-polar drug inside hydrophobic CD cavity

Surfactants & Micelles

Solubilize in micelles (e.g., polysorbates)

Salt Formation

Improves solubility for ionizable drugs

Notes:

  • Must balance solubility, stability, and physiological compatibility

  • Enhancement method should be non-toxic and appropriate for route

11. Surfactants and Micelles

  • Molecules with hydrophilic and hydrophobic regions

  • Form micelles above critical micelle concentration (CMC)

  • Used to solubilize poorly water-soluble drugs

  • Examples:

    • Steroids in polysorbates (ophthalmic)

    • Vitamins A, D, E, K in aqueous injections

12. Cyclodextrins

  • Glucose-based oligosaccharides (α-, β-, γ-CD)

  • Interior: hydrophobic | Exterior: hydrophilic

  • Bind non-polar drugs, increasing aqueous solubility

  • Enable oral absorption of otherwise insoluble drugs