Coarse Dispersions: Suspensions and Interfacial Properties

• Coarse dispersion involves suspensions, interfacial properties of suspended particles, settling in suspensions, and the formulation of flocculated and deflocculated suspensions.

Coarse Dispersion Parameters

• Particle size in molecular dispersions is less than 1 nm.
• Particle size in colloidal dispersions ranges from 1 nm to 0.5 µm (500 nm).
• Particle size in coarse dispersions is ≥0.5 µm.
• Molecular dispersions are homogenous (monophasic), while colloidal and coarse dispersions are heterogeneous.
• Molecular dispersions appear clear and transparent, colloidal dispersions are opalescent, and coarse dispersions are frequently opaque.
• Brownian movement is negligible in molecular dispersions, shows in colloidal dispersions, and doesn't show in coarse dispersions.
• Diffusion in molecular dispersions is rapid, slow in colloidal dispersions, and does not diffuse in coarse dispersions.
• Molecular dispersions pass through semipermeable membranes, colloidal dispersions pass through filter paper but not SPM, and coarse dispersions do not pass through SPM.
• Molecular dispersions can't be seen by any microscope, colloidal dispersions can be seen by electron microscope, and coarse dispersions can be seen by ordinary microscope.
• Separation in molecular dispersions occurs through crystallization, in colloidal dispersions through centrifugation, and in coarse dispersions through filtration.
• Sedimentation is not a concern in molecular dispersions, does not settle down in colloidal dispersions, and fast sedimentation of dispersed phase in coarse dispersions.
• Examples of molecular dispersions include salt solutions, glucose, and oxygen molecules.
• Examples of colloidal dispersions include protein and blood polymers.
• Examples of coarse dispersions include suspensions and emulsions.

Pharmaceutical Suspension

• Pharmaceutical suspension is a dispersion in which insoluble solids (drugs) are suspended in a liquid medium
• Suspensions are heterogeneous or biphasic systems.
• Pharmaceutical suspensions are coarse dispersions with insoluble solid particles dispersed in a liquid medium (usually water or water-based).
• Particle diameters in suspensions are generally greater than 0.5μm.
• A good pharmaceutical suspension has a particle size distribution between 0.5 - 5 μm.
• In good suspensions, the dispersed phase must be in the range of 5 - 10% W/V.

Desirable Qualities of Suspension

• Suspended material shouldn't settle rapidly and should redisperse into a uniform mixture when shaken, not forming a hard cake.
• Suspension shouldn't be too viscous for pouring from a bottle or flowing through a syringe.
• Lotions must be fluid enough to spread easily but not run off the surface.
• Suspended material should be stable, free from grittiness and microbial attack.
• Suspension should be stable physically, chemically, and pharmacologically.
• Oral suspensions should have an acceptable taste.
• Suspensions should resist microbial attack, often requiring preservatives.
• Pharmaceutical suspension is a heterogeneous system with an internal phase (particulate matter) dispersed in an external phase (suspending medium).
• The internal phase consists of insoluble particulate matter dispersed with suspending agents.
• The external phase is generally aqueous but can be organic/oily for non-oral use.

Marketed Examples

• Oral: Gelusil (Aluminum hydroxide gel, magnesium hydroxide) for antacid use.
• Intramuscular: Tricort 40 (Triamcinolone acetonide) as steroidal/hormonal treatment and allergy relief.
• Ophthalmic: Gentil (Gentamycin and hydrocortisone) for allergy.
• Rectal: Phellia/Rauson (Barium sulphate) for GIT.

Advantages of Suspensions

• Many drugs are not stable in solution form, thus suspensions are used to prepare an insoluble form of the drug to prevent degradation.
• If drugs are insoluble in water and other solvents are unacceptable, suspensions are the only choice e.g. corticosteroids.
• Adding suitable flavors and sweeteners masks unpleasant tastes, or drugs can be modified into insoluble forms.
• Insoluble solids act as drug reservoirs, continuously supplying the drug for absorption over a long period.
• Bioavailability is higher in suspensions compared to tablets or capsules due to larger surface area and high dissolution.
• Suspensions are easy to swallow and allow flexible dosing, especially for children and elderly patients which improves patient compliance.
• Bioavailability Ranking: Solution > Suspension > Capsule > Compressed Tablet > Coated Tablet

Disadvantages

• Sedimentation of solids can give a false alarm on product suitability and dose precision is hard to achieve unless unit forms are used.
• Therefore, potent drugs cannot be administered in this form and physical instability (sedimentation and compaction) causes many issues
• The product may undergo oxidation and hydrolysis, posing a chemical stability problem.
• Since suspensions are liquid dosage forms, preservation from microbial attack is essential
• Being liquid, suspensions are bulky and need proper handling and transport.

Classification of Suspensions

• Based on Proportion of Solid Particles
  • Dilute Suspension (2-10% w/v solid) e.g. cortisone acetate, prednisolone acetate.
  • Concentrated Suspension (50% w/v solid) e.g. Zinc oxide suspension.

Flocculated Suspension

• Particles aggregate by chemical bridging, forming light, fluffy conglomerates held by weak van der Waals forces.
• Achieved by adding flocculating agents and has better physical stability, but lower bioavailability compared to deflocculated systems.
• Particle interactions are influenced by ionic strength, pH, size, electrolyte valency, and electrical double layer thickness.
• Rate of sedimentation is high and sediment is loosely packed while redispersing easily when shaken.

Deflocculated Suspension

• Solids exist as individual particles exhibiting aggregation at a slower rate compared to flocculated particles.
• Has a short shelf life, but greater bioavailability and particles carry a finite charge, repelling each other which prevents aggregation
• During storage, sedimentation occurs slowly based on size and density.
• Particles form a close packing arrangement, with smaller particles filling voids between larger ones which forms a hard cake in a deflocculated system.
• Redispersing the sediment (hard cake) is hard, requiring high energy input and agitation may be insufficient.

Flocculated vs Deflocculated Suspensions

Particle-Particle Interaction and Behavior

• Potential energy curves explain the sedimentation behavior of suspensions.

Deflocculated Suspension (Particle-Particle)

• Particles carry a finite charge and when particles approach each other, experience repulsive forces to prevent particle aggregation.
• Over time, deflocculated particles exhibit very slow sedimentation due to their size and density and particles form a close packing arrangement, where the smaller particles fill he voids between the larger particles
• If the sediment's weight is high enough, the particles can come in contact and establish stronger attraction forces which will form a hard cake
• Redispersion isn't acheivable.

Flocculated Suspension (Particle-Particle)

• Particles reside at the secondary minimum, and because of this, are loosely structured.
• Interactions influenced by ionic strength, pH, size, electro/tes thickness of the electrical double layer.

Interfacial Properties of Suspended Particles

• Make sure acceptable suspensions don't exhibit settling

• Achieve b reducing the particle size to approximately 5 um

• This is so they exhibit Brownian motion

• Reduce the size range, use the following

W=∆G = ysl . ΔΑ

• YSL is the interfacial tension between the liquid medium and the solid particles.

• AA = total surface area

• AG = surface free energy

• Avoid regrouping particles, should strike a balance

• To achieve suspension

  • Charge on the insoluble solid surface and the formation of electrical double layer
  • Zeta potential of the solid surface
    • Must add electrolytes and polymers

Settling in Suspension

• Keep the particles uniformly distributed through the dispersion, consider the factors that influence velocity of sedimentation

Factors influencing particle settling

• It is ideal to stop characteristics of suspensions has highlighted the need to prevent the settling of particles
• Brownian
  • Brownian movement of particles prevents sedimentation -If size of the particles is 2 to 5 um
• Theory of sedimentation

Rate of sedimentation = d² (p1 - p 2) g/18η

Where,

d = diameter of the particles, cm p1= density of the dispersed phase, p2 = density of the dispersion medium, η = viscosity of the dispersion medium G= acceleration due to gravity, 980.7

Settling factors to watch

• If reduced particle size (one half its original size) sedimentation rate decrease 4x

• Density: make the density of a medium equal to the density of solids avoid settling

• -- High viscosity advantages

• Enhance physical stability

• Inhibits diminishing diminished movement of particles

• Avoid metastable crystals

• -- Disadvantages

• Sediment harder to re-disperse

• Absorption of durgs are diminished

• Handling difficult

Physical Stability

• Particles remain uniformly distributes throughout the dispersion no signs
• Achieve condition easy by just shaking it

Extent of sediemtnaiotn

• Quanttively expressed by paramesters apply only fluccolalation

Sedimentatiotn VOULME F

• What volume ultimateyl settles in sediemntatiotn

Ultemate volume of the sediment / initial volume of the suspension

• Can be measurede when the height of sediemtn at both measures

Degree of folucatiot

• Provides some idea of the entent
• Evaluate redispresibality by mechacnial shaker

Formulation of Suspensions

• The fomrulatiotn relies on weather disired suspension

• Structured ehilsd

• Disperiation is critical for hyrdotphoic powders

• Water miscice collcits alcohols

• -- Structed veciles

• structured vecules

• Non ionin density often increase vechule addition

Controlled Flocciation suspension

• Floccuaiiton can be produce d by a ddutoon floccinatio
• Most dipersed aprtivcles psos charge that can
  • reduced
  • surfactatnts -Polymer

Electrolyctes

• The like chars rists colliosno

Suracantaan

• The conactaitiotn is cuicla
• Polymers

-Apsrotion

• Xanthan