Suspensions 2
Page 1: Introduction to Suspensions
Title: PHAR 202 Towards Unbounded Thinking: Suspensions
Instructor: Carol Yousry, Ph.D.
Affiliation: School of Pharmacy, NGU
Date: Oct-24
Page 2: Learning Outcomes
Main Objective: Discuss fundamental colloid science to design, prepare, and assure quality of pharmaceutical products.
Page 3: Learning Objectives
By the end of this lecture, you should be able to:
Explain the usefulness of suspensions in pharmacy.
Describe properties of a good suspension.
Discuss formulation, stability, and manufacturing considerations.
Explain the utility of viscosity-enhancing, wetting, and flocculating agents with examples.
Page 4: Definition of Suspension
Suspension: A dispersion of insoluble solid particles in a liquid.
Particle Size: Generally >1 μm up to 10 μm.
Comparison: Different from a colloidal system (particle size < 1 μm).
Page 5: Reasons for Using Suspensions
Poor Solubility: Some drugs cannot be made into solutions.
Taste Masking: Unpleasant tastes may be less noticeable in a suspension (e.g., Paracetamol).
Stability: Drugs may be more stable in suspension than in solution or as solids.
Page 6: Properties of a Good Suspension (Part 1)
Particle Size: Small and uniform size (1-10 µm) for a smooth texture.
Comparison: A good suspension is not gritty, while a bad suspension has overly large or varied sized particles.
Page 7: Properties of a Good Suspension (Part 2)
Homogenous : Even distribution of particles after shaking; ensures consistent dosing.
Visual Example: A good suspension maintains proportional doses, whereas a bad one exhibits significant variations.
Page 8: Properties of a Good Suspension (Part 3)
Viscosity: Must be sufficient to reduce sedimentation rate, yet remain pourable.
Re-dispersibility: Ease of dispersion upon shaking is crucial for maintaining suspension integrity.
note: the higher the viscosity, the lower the sedimentation rate
Page 9: General Formulation Considerations
Key Factors:
Physical characteristics of the drug.
Solubility and dissolution issues.
Dispersibility aspects.
Impact of added excipients.
Physical and chemical stability—both short-term and long-term.
Page 10: Making a Suspension
Initial Steps: Start with the drug having small and uniform particles; maintain small amounts in solution.
Temperature Effects: Changes in temperature can alter solubility and lead to Ostwald ripening, where smaller particles dissolve and larger ones grow.
Page 11: Solubility & Dissolution Issues
Ostwald Ripening: Alters particle size and distribution; prevention through flat solubility profiles.
Flat Solubility Profile: Preferable for lower aqueous solubility drugs, achievable with antisolvents.
Page 12: Dispersibility & Surface Wetting
Key Concept: The behavior of a liquid droplet on a single solid particle.
High interfacial tension(liquid doesn’t spread around particle) leads to poor suspension.
Low interfacial tension(liquid spreads around the particle) indicates good dispersibility.
Page 13: Practical Example
Relevance: Remember the importance of proper dispersion techniques—illustrated with a reference to making Turkish coffee.
Page 14: Assessing Dispersibility
Contact Angle Assessment: Evaluates dispersibility.
Values < 90° indicate good wetting and dispersibility.
Values > 90° show poor wetting.
Page 15: Enhancing Dispersion
Wetting Agents Role: To facilitate the dispersion of water-insoluble drugs by lowering interfacial tension.
Page 16: Wetting & Dispersion Visualization
Effects of Wetting Agents: Enhance dispersion of hydrophobic particles by reducing clumping and facilitating integration into the aqueous medium.
Page 17: Function of Wetting Agents
Preventing Containment Adhesion: Coats particles to decrease their tendency to cling to containers, facilitating better dosing.
Page 18: Types of Wetting Agents
Surfactants: Used below CMC (Critical Micelle Concentration).
Examples: Polysorbates (Tweens), Sorbitan esters (Spans), Sodium lauryl sulfate.
Page 19: More Wetting Agents
Hydrophilic Colloids: Provide coating to solid particles.
Examples: Acacia, Bentonite, Cellulose derivatives.
Page 20: Additional Wetting Agents
Simple Solvents: Aid in displacing air from powder pores.
Examples: Alcohols, Glycerol.
Page 21: Sedimentation in Suspensions
Measurement of Sedimentation: Ratio of sediment layer volume to total volume (R) quantifies sedimentation.
R= HEIGHT OF SEDIMENTED LAYER/ TOTAL HEIGHT OF SUSPENSION
Page 22: Sediment Ratio Calculation
Sediment Ratio: Ratio formulated as either:
Volume of sedimented layer (Vs) / Total suspension volume (Vt)
Height of sedimented layer (h) / Initial height of suspension (h0)
Page 23: Velocity of Sedimentation
Observation of Sediment Layers: At different time intervals (e.g., 0, 15, 30 min, 1 h, 6 h), measuring height for sediment analysis.
Page 24: Understanding Sedimentation Velocity
Stokes’ Law: Overall sedimentation velocity depends on particle radius, densities, viscosity, and gravity.
a = the radius of the solid particles;
σ = the density of the solid;
ρ = the density of the liquid;
η = the viscosity of the liquid;
g = the acceleration due to gravity.
Page 25: Desired Sedimentation Pattern
Ideal Characteristics:
Slow sedimentation by increasing viscosity to retain dispersibility without compromising pourability.
Page 26: Suspending Agents
Role of Viscosity Enhancers: Different agents can alter sedimentation patterns and affect dosing precision.
Page 27: Examples of Suspending Agents
Common Agents: (viscosity enhancers)
Polysaccharides (e.g., Acacia, Xanthan gum),
Celluloses (e.g., Methylcellulose),
Hydrated silicates (e.g., Bentonite).
Carbomers and silicon dioxide (Aerosil).
Page 28: Considerations for Suspending Agents
Trade-offs: Over-viscous suspensions may hinder pouring; hence balance needed with potential flocculating agents.
Page 29: Suspension Classification
Deflocculated vs Flocculated: Key difference in the presentation and behavior of particles suspended.
Page 30: Characteristics of Deflocculated Systems
Settling Characteristics: Slow sedimentation which can lead to caking and complicated redisperse upon settling.
Page 31: Characteristics of Flocculated Systems
Behavior Upon Settling: Rapid settlement leading to ease of redisperse, making them preferable in pharmaceuticals.
Page 32: Comparing Flocculated vs Deflocculated Systems
Key Differences:
Deflocculated: Slow settling, difficult to redisperse, higher risk of caking.
Flocculated: Quick sedimentation, easy to redisperse, less caking and presents cloudy appearance.
Page 33: Visual Sediment Comparison
Representation of Sediment Dynamics: Comparison in ratio and height of sediment in deflocculated vs flocculated systems.
Page 34: Formulating Flocculated Systems
Strategy Choices: Formulators can adjust viscosity and density to manage rates of sedimentation for optimal suspension performance.
Page 35: Importance of Education on Shaking
Patient Education: Emphasizing shaking before dosing for maintaining proper suspension characteristics and dosing accuracy.
Page 36: Role of Flocculating Agents
Function: Minimize caking while aiming for a partially flocculated system that enhances redisperse potential.
Page 37: Examples of Flocculating Agents
Types of Agents:
Include electrolytes (e.g. sodium acetate),
surfactants, (ionic or non-ionic)
polymers, (starch, alginates, cellulose derivatives)
carbomers or silicates.
Page 38: DLVO Theory
Key Concept: Describes the multiple interactions in suspensions based on the electrical double layer around particles.
Page 39: Exploring the Electrical Double Layer
Details on Layer Structure: Composed of various planes that contribute to the overall behavior of particles in suspension.
Page 40: DLVO Potential Interaction Profiles
Attraction vs Repulsion: Visual understanding of energy interaction profiles based on particle separation.
Page 41: Effects of Zeta Potential Changes
Connections to Dosing: Zeta potential influences suspension reproducibility and sedimentation behavior; management is critical for effective formulations.
Page 42: Moderate Electrolyte Effects
Resulting Changes: Higher +ion concentrations decrease zeta potential, affecting stability and promoting flocculation.
Page 43: High Electrolyte Effects
Observations: High concentrations lead to aggregation and reduced charge stability among particles, complicating suspension integrity.
Page 44: Zeta Potential Dynamics
Isoelectric Effects: Closer zeta potentials lead to more pronounced flocculation effects within the suspension.
Page 45: Example of Bismuth Subnitrate Suspension
Initial State: Deflocculated due to positively charged surfaces and controlled by adding KH2PO4 to manage zeta potential.
Page 46: Managing Zeta Potential in Bismuth Suspension
Zeta Potential Control: As KH2PO4 increases, zeta potential transitions from positive to negative, crucial for achieving a non-caking flocculated state.
Page 47: More on Zeta Control
Key Aspect: Accurate control of the amount of electrolyte added to achieve desired flocculated properties in the suspension.
Page 48: Recap on Flocculating Agents
Re-emphasis: The range of agents, including electrolytes and various surfactants and polymers, that affect sedimentation characteristics.
Page 49: Surfactants' Influence
Mechanism: Neutralization of surface charge through surfactant addition, affecting particle interactions.
Page 50: Surfacing Effects Explained
Concentration Dynamics: Beyond CMC leads to micelle formation; below CMC aids in inter-particle interactions.
Page 51: Bridging Model Elaborated
Inter-particle Behavior: Explains the series of reactions leading to floc formation and particle bridging under optimal polymer dosages.
Page 52: Managing Surfactant Concentration
Risk Mitigation: Importance of controlling polymer levels to prevent re-stabilization of deflocculated states.
Page 53: Formulation Excipients Summary
Function Overview:
Wetting Agent: Ensure uniform particle size and homogeneity.
Suspending Agent: Assure slow sedimentation rate.
Flocculating Agent: Enhance redisperse characteristics.
Additional excipients: Buffers, stabilizers, preservatives.
Page 54: Manufacturing Considerations
Critical Stage: Initial dispersion of powdered drug with wetting agent is imperative to avoid caking; packaging requires stirred conditions to keep suspension homogeneous.
Page 55: End of Lecture
Questions and Engagement: Invitation for learning moments and inquiries regarding suspensions.
Page 56: Recap of Critical Points
Suspension Definition: Characterized by small uniform size, homogeneity, slow sedimentation, and redispersibility.
Key Considerations: Involves solubility, dispersibility, excipient effects, application of DLVO theory, and surfactants.
Page 57: Further Reading
References for More Information:
Aulton and Taylor, Aulton's Pharmaceutics, 5th ed, Elsevier, 2017.
Florence and Attwood, Physicochemical Principles of Pharmacy, 6th ed, Pharmaceutical Press, 2015.