Excipients for Liquid Dosage Forms

Lecture by Urooj Ahmed Khan

Delhi Institute of Pharmaceutical Sciences and Research (DIPSER)

Learning Objectives

• Excipients in monophasic and biphasic liquid dosage forms
• Mechanism of actions
• Surfactants used in liquid dosage forms
• Determination of HLB value of surfactants

Introduction

• Liquid Dosage Forms: Two types: monophasic and biphasic
• Target user: Geriatric or pediatric population
• Types: Solutions, suspensions, emulsions
• Prepared by dissolving or suspending substances in aqueous or non-aqueous vehicles

Monophasic Liquid Dosage Forms

• Solutions: Liquid preparations with soluble chemical substances
  • Must be in solution form for better absorption
  • Challenges include solubility and stability

Excipients for Monophasic Liquid Forms

Vehicles

• Aqueous Vehicles: Water, polyhydric alcohols, hydroalcoholic solutions, buffers
  • Water: Portable water, purified water (USP standard), water for injection (parenterals)
  • Alcohol: Ethyl alcohol (dissolves alcohol and water-soluble drugs)
  • Glycerol: Co-solvent to solubilize hydrophobic drugs, improves viscosity, taste masking agent
• Oily Vehicles: Vegetable/mineral oils, organic oily bases, emulsified bases
  • Lipid-based vehicles: Solubilize hydrophobic drugs, aid in dissolution and absorption

Solubilizers

• Modify water polarity to dissolve non-polar drugs
• Reduce interfacial tension between aqueous solutions and hydrophobic solute
• Examples: Sugars, sorbitols, alcohols (ethanol, propylene glycol, PEG-400)

Complexing Agents

• Enhance solubility by forming inclusion complexes
• Example: Cyclodextrin
  • Forms non-covalent interaction with drug molecules
  • Advantages: Improved solubility, stability, taste masking

Buffering Agents

• Maintain pH for compatibility and stability
• Concentrations of 0.05-0.5 Molar are sufficient
• Factors influencing pH: co-solvents, dilution, ionic strength, temperature
• Buffer types: Citrates, phosphates, carbonates, tartrates

Antifoaming Agents

• Prevent foam formation during manufacturing and reconstitution
• Example: Cymethicone
  • Works by lowering surface tension, causing destabilization of foam
  • Effective in non-aqueous systems

Excipients for Biphasic Liquid Forms

Overview

• Includes suspensions and emulsions
• Characterized by an interface between phases
• Goal: Reduce positive interfacial free energy to zero

Wetting Agents

• Help disperse solid particles into liquid vehicle
• Improve solvent penetration in solid particles
• For aqueous vehicles: Alcohol, glycerin
• For non-aqueous vehicles: Mineral oil

Deflocculants and Dispersing Agents

• Maintain discrete units of dispersed particles
• Example: Lecithins
• Prevent caking and improve re-dispersibility

Flocculating Agents

• Reduce zeta potential of charged particles
• Example: Electrolytes like sodium chloride, aluminum chloride
• Forms porous structure, aiding in redispersion

Suspending Agents

• Prevent aggregation and settling of particles
• Examples: Cellulose derivatives, natural/synthetic gums, clays
  • Protective colloids: Increase zeta potential, form mechanical barrier
  • Clays: Form colloidal dispersions, neutralize acids, require preservatives

Emulsifying Agents

• Reduce interfacial tension, prevent droplet coalescence
• Mechanisms: Interfacial barrier, monomolecular or multimolecular film, electrical repulsions

Viscosity Modifiers

• Ensure stability by manipulating flow characteristics
• Additives: Gums, clays, synthetic polymers
• Influences: Particle size, composition, emulsifier, rheology

Determination of HLB Values

• Hydrophilic-Lipophilic Balance (HLB)
• Determines suitability of emulsifiers for various applications
• Calculation: Based on structural formula or empirical formulae
• Application: Anti-foaming agents, water-in-oil emulsifiers, wetting agents, detergents, solubilizing agents

Conclusion

• Formulation of optimal dosage forms requires understanding solubilization and stabilization
• Use of excipients like wetting, suspending, and emulsifying agents is essential
• Mechanisms and properties of each excipient help in developing stable monophasic and biphasic formulations.