Pharmaceutical Rheology

Main ideas and concepts (pharmaceutical rheology)

Rheology (core concept)

• Rheology is the study of how matter flows and/or deforms under applied stress.
• It explains how materials respond to force: whether they flow, whether flow is uniform, and whether their internal character changes (e.g., becoming more viscous/thickened).

Why rheology matters in pharmaceutics

• Used to understand and develop pharmaceutical formulations (dosage forms).
• Key application areas:
  • Pharmaceutical processing (e.g., mixing) depends on flow behavior.
  • Filling and packaging depend on viscosity/flow properties.
  • Stability and bioavailability can change with rheology:
    • If a material becomes too thick, it may not produce a proper absorption profile → bioavailability decreases.
  • Drug release differs between:
    • solution vs solid vs gel/network forms
    • flowable forms allow greater freedom for solubilization than tightly structured networks.

Fundamental terms

• Elasticity
  • Restores shape after force is removed (reversible deformation).
• Viscosity
  • Resistance of a liquid to flow.
• Deformation types
  • Elastic (reversible): returns to original form (example: rubber).
  • Plastic (irreversible/permanent): does not regain original shape/position.

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Newton’s law of viscous flow (and what viscosity means)

Relationship (conceptual description)

• When shear is applied, fluid particles move.
• Rate of shear is the gradient of velocity with distance: dv/dx.
• Shear stress (force per unit area) is proportional to rate of shear:
  • Shear stress = viscosity × (rate of shear)
  • viscosity acts as the proportionality constant.

Units described

• Shear stress: force/area, dynes/cm² (CGS)
• Rate of shear: cm/s
• Viscosity (CGS): dyn·s/cm² → poise
• SI units
  • stress: pascal (Pa)
  • viscosity: pascal-second (Pa·s)
  • conversion: 1 Pa·s = 10 poise

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Fluid classification by flow behavior

1) Newtonian fluids

• Follow Newton’s law of viscous flow.
• Key behavior
  • Shear stress vs shear rate is linear.
  • Viscosity is constant, independent of shear rate.
• Examples given
  • water, glycerine, benzene, alcohol, syrup, very dilute colloidal solutions

2) Non-Newtonian fluids

• Do not follow Newton’s law.
• Further divided into:
  • Time-independent non-Newtonian fluids
  • Time-dependent non-Newtonian fluids

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Time-independent non-Newtonian fluids

(Visco behavior changes with shear conditions, but not with time in the described sense.)

Plasticity (yield stress behavior)

• Material behaves as if it has a yield value.
• No flow until stress exceeds a yield threshold.
• After yield, it begins to flow and can behave more like a Newtonian fluid beyond that point.
• Associated with flocculated structures:
  • floccules at rest → shear breaks structure/freedom increases → flow starts.
• Examples given:
  • suspension of zinc oxide/mineral oil (paint/focculated suspensions referenced)
  • flocculated suspensions (also discussed as concentrated systems)

Pseudoplasticity (shear thinning)

• As shear stress increases → viscosity decreases.
• Polymer/molecules align under shear; at rest they are randomly arranged.
• No yield value concept.
• Examples given:
  • tragacanth solutions, sodium alginate, cellulose derivatives
  • weakly flocculated suspensions
  • polymeric suspensions
  • natural/synthetic gums and polymers such as microcrystalline cellulose, tragacanth, sodium alginate

Dilatancy (shear thickening)

• As shear rate increases, viscosity increases (greater resistance to flow).
• Material dilates/increases volume under stress due to particle expansion.
• Example given:
  • CMC (carboxymethyl cellulose) described as dilatant, generally deflocculated

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Time-dependent non-Newtonian fluids

(Structure rebuilds/breaks over time; behavior depends on how long shear acts.)

Thixotropy

• Shear-thinning over time due to time-dependent breakdown/rebuilding of structure.
• Described as reversible and isothermal.
• Commonly associated with gel ↔ sol transformations:
  • agitation causes gel-to-sol conversion (viscosity decreases)
  • removal of agitation allows return to original state (viscosity increases back)
• Rheogram depends on:
  • rate of increasing/decreasing shear
  • duration under a given stress

Reopexy

• Time-dependent increase in viscosity with continued shearing.
• Observed during sol → gel conversion:
  • longer shearing time → viscosity increases

Anti-thixotropy (negative thixotropy)

• Reversible, time-dependent increase in viscosity at a particular shear rate.
• Attributed to increased collision frequency → increased interparticle bonding over time.

“Eopexy” (as described in the transcript)

• Presented as occurring in an anti-thixotropic system:
  • gentle vibrations/shaking/mild turbulence accelerate reformation from gel state to solution state.

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Gel–sol transformation summary (as presented)

• Gel + applied stress → sol
• After removing stress, it can go to either:
  • Thixotropy: slow return to gel (sol → gel slowly)
  • Rheopexy: rapid thickness change (described as faster sol ↔ gel behavior)
• The rate of conversion determines whether behavior is thixotropy- or rheopexy-dominated.
• Mentioned scenario with “salt”:
  • lower-viscosity application of shear changes conversion pathways and speeds (as described).

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Examples of rheological behaviors (as a set/list)

• Newtonian: water, glycerine, benzene, alcohol, syrup, very dilute colloid solutions
• Plastic bodies: suspension of zinc oxide and mineral oil, paint, flocculated suspensions
• Pseudo-plastic systems (shear thinning): natural/synthetic gums and polymers such as microcrystalline cellulose, tragacanth, sodium alginate; CMC discussed separately
• Dilatant system (shear thickening): CMC described as dilatant, generally deflocculated

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Viscosity measurement methods

Capillary viscometers (most common)

• Determine viscosity by measuring flow rate through an orifice/capillary.
• Record time required for the material to flow through the capillary/orifice.
• Predict viscosity from that flow time.

Density-dependent viscometers

• Measure viscosity using a falling object’s velocity through a liquid under gravity.
• Different liquids resist falling differently (e.g., water vs glycerine).
• Use falling velocity to infer viscosity.

Rotational viscometers

• Measure viscosity based on resistance offered by a rotating element immersed in the fluid.
• Viscosity correlates with the measured resistance/response.

One-point vs multipoint instruments

• One-point measurements suitable for non-Newtonian fluids
  • includes capillary viscometers and falling sphere viscometers (as stated)
• Multipoint instruments
  • can be used for both Newtonian and non-Newtonian systems

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Viscoelasticity (additional key concept)

Definition

• Materials showing both viscous and elastic properties are viscoelastic.

Examples mentioned

• Pharmaceutical formulations such as lotions, creams
• Biological examples: blood and sputum

Behavior under stress

• Short-time stress → deformation; after stress removal → elasticity restores original shape.
• Long-time stress → may cause permanent deformation and loss of elasticity.

Three listed properties

• Hysteresis
  • Continuous change in configuration, transitioning between viscous and elastic behavior and then returning.
• Creep
  • Time-dependent strain at constant stress.
• Stress relaxation
  • Time-dependent stress at constant strain.

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Practical takeaways / practical utility

Understanding rheology guides:

• which materials to use
• how to process them (mixing, handling)
• packaging design
  • e.g., narrow-mouth vs wide-mouth containers depending on flow behavior (lotions-style containers mentioned for thicker materials)
• operational efficiencies in warehousing and transportation
• ensuring product stability and usability for therapeutic outcomes

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Speakers / sources featured

• Speaker/Presenter: Not explicitly named in the subtitles (lecturer delivering the content)
• Primary referenced source concepts:
  • Newton’s law of viscous flow (no direct author attribution beyond Newton’s principle)