Rheology in Pharmacy

Rheology

• Rheology is the study of flow.
• The Greek word "rheo" means "flow."
• Heraclitus, from writings by Simplicius, said, "everything flows." (Panta rei)
• Viscosity is the resistance to flow.
• Higher viscosity means greater resistance to flow.
• Rheology is used to study paints, inks, doughs, road building materials, cosmetics, dairy products, and other materials.

Rheology in Pharmacy

• Rheology is applied to formulate, analyze, and study pharmaceutical products like:
  • Emulsions
  • Pastes
  • Suppositories
  • Tablet coatings
  • Medicinal and cosmetic creams
  • Lotions

Types of Flow

• Newtonian system: Viscosity is constant, regardless of the rate of shear.
• Poise (or centipoise): units of viscosity.
• Gcm-1sec-1 or g/cmsec: these are units of viscosity
• 1 centipoise (cp) = 0.01 poise
• Fluidity is the reciprocal to viscosity.

Kinematic Viscosity

• USP kinematic viscosity is absolute viscosity.
• Kinematic viscosity = (dynamic viscosity) / (density)
• Units: Stoke (s) and Centistoke (cs).
• Measurement scales: arbitrary scale like Saybolt, Redwood, Engler.

Viscosity Enhancing Agents

• Agents that thicken or increase the viscosity of substances.
• Examples of agents: Acacia, Agar, Bentonite, Carbomer, SCMC, CCMC, Carrageenan, Dextrin, Gelatin, Povidone, Pectin, Colloidal silicon dioxide, Starch, Tragacanth, Xanthan gum.

Temperature and Viscosity

• Gas viscosity increases with temperature.
• Liquid viscosity decreases with increasing temperature.
• Activation energy is the energy needed for flow between molecules.

Non-Newtonian Systems

• Flow properties that change in response to changes in shear rate.
• Examples of these systems:
  • Liquid and solid heterogeneous dispersions
  • Colloidal solutions
  • Emulsions
  • Liquid suspensions
  • Ointments
  • Other similar products.
• Analyzed via rotational viscometers.

Three Classes of Flow

• Plastic flow
• Pseudoplastic flow
• Dilatant flow

Plastic Flow

• Bingham bodies are substances that exhibit a yield value.
• They behave as solids until a certain force is applied (yield value), then flow like a liquid.
• Mobility is the slope of the rheogram (which is similar to fluidity); the reciprocal is called plastic viscosity (U).
• Presence of flocculated particles in concentrated suspensions will increase yield value.

Pseudoplastic Flow

• Apparent viscosity decreases as shear stress increases.
• Examples of materials with pseudoplastic flow:
  • Paper pulp in water
  • Latex paint
  • Ice
  • Blood
  • Syrup
  • Molasses.

Dilatant Flow

• Suspensions with a high concentration of dispersed solids exhibit increased resistance to flow as shear rate increases.
• Examples of dilatant systems:
  • Suspensions of corn starch in water
  • Suspensions of sand in water.
• Shear thickening behavior - when stress is removed, a dilatant system returns to its original state of fluidity. Usually includes high concentration of small, defloculated particles (exceeding 50%).
• Shear stress dilates the system or expends the bulk of the system.
• Dispersion of solid particles to high-speed mixers, blenders or mills is easier due to the increase in volume caused by the dilatant flow.
• May cause equipment issues in processing due to solidification during high shear conditions.

Thixotropy

• Apparent viscosity decreases over time with stress application.
• Examples: Some clays, some drilling mud, many paints, some synovial fluids, honey under certain conditions.
• Thixotropy is a shear thinning system, which causes the gel-to-sol transformation (a process where a system turns from a gel-like to a liquid-like state when the stress applied to it increases).
• Gel-to-sol transformation due to stress is not instantaneous; it is progressive; the consistency progressively reforms.

Negative Thixotropy/Antithixotropy

• Negative thixotropy (antithixotropy) involves the opposite effect.
• Magnesia magma may increase thickness with increased shear rate.
• Antithixotropy systems typically have lower solid content (1-10%) and are flocculated.
• Dilatant systems are defloculated and commonly contain >50% by volume of solid phase .

Rheopexy

• Apparent viscosity increases with stress duration (e.g., whipped cream).
• More readily forms a gel in shaken/stirred mixtures than in an unperturbed state.
• Rheopectic system gels reach an equilibrium state

Thixotropy in Formulation

• A desirable property in liquid pharmaceutical systems.
• Enables easy pouring and spreading in containers.
• Well-formulated thixotropic suspensions do not settle out readily and remain fluid long enough for dosing, regaining rapid consistency when shaken.
• Examples of formulation: emulsions, lotions, creams, ointments, and parenteral suspensions (IM).

Suspension Stability

• Thixotropy relates to rate of settling (lower thixotropy means faster settling).
• Concentrated parenteral suspensions (e.g. 40-70% w/v procaine pen G) have inherent thixotropy & shear thinning which allows it to pass through hypodermic needles.
• Drug formation in the site of injection can be affected by thixotropy, resulting in slower drug release.

Determination of Rheological Properties

• Newtonian systems use one-point instruments measuring shear stress and rate of shear.
• Non-Newtonian systems use multi-point instruments because viscosity varies with shear rate.
• Viscometers are instruments used to measure viscosity. Not all are suitable for non-Newtonian systems.

Choice of Viscometer

• Tackiness, stickiness, and spreadability challenges precise measurement with conventional approaches.
• Pseudoplastic materials require instruments capable of measuring across a wide range of shear rates.

Capillary Viscometer

• Instrument measures time required for a liquid to flow through a capillary tube under gravity.
• Used for high-viscosity liquids; USP often suggests this for such substances.

Falling Sphere Viscometer

• Instrument measures viscosity by noting the rate at which a sphere falls through the liquid.
• Can test high-viscosity materials (0.5 to 200,000 poise).

Cup and Bob Viscometer

• Instrument measures shear stress and shear rate via rotating bob within a cup.
• Measures viscosity in rotational viscometers, such as Brookfield viscometers; usable with both Newtonian and non-Newtonian substances, especially pastes & semisolids.
• Disadvantage of variable shear stress across sample.

Plug Flow

• Gap between cup and bob is minimized to avoid plug-like flow (important in pastes and concentrated suspensions passing through orifices, such as extrusion of toothpaste).

Cone and Plate Viscometer

• Measures shear rate with a cone and plate; smaller angle cones are often preferred.
• Advantages are time saving when cleaning or filling, better temperature control during sample runs, and measurements with small samples (0.1-0.2 mL) which helps with semisolids.

Viscoelasticity

• Material exhibiting both liquid-like viscous properties and solid-like elastic properties.
• Examples include creams, lotions, ointments, suppositories, suspensions, colloids, emulsifying and suspending agents, biological materials (e.g. blood, sputum, cervical fluid).
• Kelvin materials show a parallel combination of elastic and viscous effects, exhibiting a well-defined "resting shape" when the stress is removed.

Psychorology

• Study of material properties relevant to how they feel, and how they appear.
• Organoleptic evaluation covers visual evaluation (e.g., color, odor).
• Dermatologists classify ointments which includes their appearance (soft, stiff), and their use or applications as ophthalmic ointments, medicated ointments, or application for moist ulcerative condition .

Applications to Pharmacy

• Rheology is used in pharmaceutical formulations for mixing, particle size reduction, passing through orifices (e.g. pouring, packaging in bottles, hypodermic needles), fluid transfer (e.g. pumping, pipes), and stability of disperse systems.
• Other areas using rheology include flow of quasi-solids or semisolids (e.g., spreading, adherence/removal from jars/tubes), and flow of bulk solids (e.g., processing capacity, efficiency of powders in hoppers, die cavities, capsules).
• Polymer solutions also use rheology (e.g. dermatological bases, ophthalmic preparations, wetting solutions, tear replacement for dry eye syndrome).
• States of liquid, such as pendular state, funicular state, capillary state, and liquid droplet state are important. These relate to how liquids or semi-solid materials interact with surfaces or containers.
• Substances can be identified and quantified in terms of their viscosity at room temperature.

Explore the fascinating field of rheology and its applications in pharmacy. This quiz covers basic concepts of rheology, types of flow, and the importance of viscosity in the formulation of pharmaceutical products. Test your knowledge on how rheology influences the behavior of various materials used in healthcare.