Liquid Dosage Forms - Disperse Systems: Suspensions Flashcards
What is dispersion
A system in which a dispersed phase is distributed through a continuous phase
Disperse systems consist of
- Suspensions
- Emulsions
- Aerosols
- Gels
Dispersions can be classified based on size as:
- Molecular dispersion < 50 A, homogeneous system
- Colloidal dispersion 50-2000A, heterogeneous system
- Coarse dispersion > 2000A, heterogeneous system
What is aggregation
Collection of particles into a group
What is coagulation
Particles closely aggregated and therefore, difficult to redisperse
What is flocculation
Open aggregates with particles remaining apart by a small distance
What is suspension
2 phase systems comprising solid particles (disperse phase) dispersed in a liquid (continuous phase or dispersion medium)
Suspensions can be divided into
- Coarse suspensions - contain visible solids
- Colloidal suspensions - no visible solids to naked eye - lyophilic (high affinity to the continuous phase)/lyophobic (lack of attraction, thermodynamically unstable and formed by aggregation of small particles/comminution of large particles)
What is a pharmaceutical suspension
Preparations containing finely divided drug particles distributed uniformly throughout a vehicle in which the drug exhibits minimum solubility
Advantages of suspensions
- Chemical stability: more stable than in solution
- For drugs that are insoluble
- More palatable compared to solution
- Prolong drug action
Disadvantages of suspensions
- Physical instability - settle over time -> lack of uniformity and accuracy of dose
- Sedimentation and compaction cause problems
- Bulkiness of the drug as liquid is added
- Difficult to formulate
Features desired of suspensions
- Should satisfy the qualities of all pharmaceutical properties - therapeutic efficacy, chemical stability, permanency of the preparation, esthetic appeal
- Particle size should be small with uniform size and remains fairly constant on standing
- Should pour readily from its container after shaking
- Must remain homogeneous for intake
- Should settle slowly and readily redisperses when shaking
Main ingredients for suspensions
- Drug - drug particles ideally have uniform size or distribution; drug surface (hydrophilic/hydrophobic)
- Wetting agent - depends on the type of drugs (hydrophilic-solvents/hydrophobic-surfactants) - displace air from the particle surface and separate each particle from adjacent particles for wetting, reduce surface tension of an aqueous medium, partially cost the surface/form a complete monolayer on the suspension particles
- Flocculating agent - enable suspension particles to link together in loose aggregates/flocs
- Suspending agent - increase viscosity and retard sedimentation, must be dispersed in the aqueous vehicle to avoid formation of clumps
Examples of suspending agents
cellulose derivatives, clays, natural gums, polymers
Examples of flocculating agents
electrolytes, surfactants and polymers
Ways to control sedimentation
- increase the concentration of suspending agent
- proper selection of suspending agent
- increase viscosity of the suspension vehicle
- decrease the particle size -> slow settling rate
- increase particle separation -> prevent clumping/caking upon settling
Particle size reduction can be done by
- Micropulverization: 10-50um
- Jet milling/micronizing: <10um
- Spray drying: extremely small dimensions
How to decrease sedimentation rate
decrease the differences in densities between the suspended particle and suspension medium
Describe suspension interactions
- Surfactants (wetting agents) used to wet the suspension particle will exist in an equilibrium between surfactant adsorbed on the particle surface, monomers in solution, and surfactant in micelles
- Polymers (suspending agents) will exist in equilibrium with polymers in solution
- Electrolytes that affect the adsorption of surfactants and polymers can be adsorbed onto the suspension particle surface directly affect the surface charge of the particle
2 states that suspension can exist in
- Deflocculated state: each suspension particle exists independently and behaves as a single particle - no interaction
- Flocculation state: suspension particles attract each other and form loosely bound aggregates/flocs
Models to describe flocculation
- Electrostatic model of flocculation
- Polymer model of flocculation
(Draw)
Deflocculated VS Flocculated
Deflocculated
- Particles exist as separate entities
- Sedimentation is slow, particles settle separately
- Sediment is formed slowly from the bottom of the container
- Sediment eventually becomes caked due to weight of succeeding layers of sediment
- Remains suspended for relatively long time, remains cloudy
Flocculated
- Particles are loose aggregates
- Sedimentation is rapid, particles settle as large flocs
- Sediment formed rapidly from top of container
- Sediment is loosely packed and easy to redisperse
- Somewhat unsightly as there is obvious, clear supernatant
Preparation of flocculated suspensions
Depends on the drug type and product desired
- use clays like bentonite: act as a support for the floc
- alteration in pH to minimize solubility
- electrolyte - electrical bridge
- surfactants - induce process and increase sedimentation volume
What are important to note about dispersion medium
- Rapid settling can cause it to be difficult to measure accurate dose and produces pharmacologically inelegant preparation
- Suspending agents give structure to dispersion medium - add viscosity but must ensure that thickener does not bind drug or is too viscous as it prevents agitation and pouring of suspension
Steps to prepare suspensions
- Add wetting agent to the particles: Use alcohol, glycerin, propylene glycol, surfactants to displace air
- Add all water soluble materials to dispersion medium
- Add dispersion medium to wetted particles in portions
- Preservatives can be added to prevent bacterial growth
- Use blender or mixer to ensure uniformity of suspension (liquid phase -> dispersed phase)
Packaging and storing suspension
- Wide-mouth containers
- Containers should have adequate space above the liquid for thorough mixing and pouring
- Tight containers protected from freezing, excessive heat or light
- Should be shaken before use
Bulk surface properties for disperse systems
- surface tension
- interfacial tension
- wetting
- adsorption
Examples of wetting agents
acacia, taragacanth, sodium lauryl sulfate (anionic), polysorbate 80 (nonionic)
