4.3.1 Compounding – Rheology
The Fundamentals of Rheology
Learning Outcomes
Be able to:
- Explain rheology and different types of flow behaviour of pharmaceutical liquids
- Describe Newton’s law of flow and its application
- Define different terms and concepts of Non Newtonian Fluids
- Identify Newtonian and Non Newtonian fluids from a rheogram
- Apply rheology in pharmaceutical sciences.
Viscosity
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The science and physics of how liquids flow and solids are deformed form the basis of what is known as rheology.
But what is the importance of rheology in the pharmaceutical industry? It is important to understand the behaviour of fluids and other materials in pharmaceutical manufacturing and formulation. The viscosity of a suspension changes the rate of sedimentation, if the viscosity is too low the drug particles may settle quickly making the dosage inconsistent, a higher viscosity ensures a more uniform suspension.
The viscosity is also used as a measure of resistance to flow. In practical terms this reflects on pouring a dose from a bottle or drive a dose through a syringe. Therefore, controlling viscosity is crucial to ensure effective dosage and administration.
Newtonian Fluids
What makes a fluid either “Newtonian” or “non-Newtonian”? In 1687 Sir Isaac Newton described Newtonian Fluids in Newtons Law of Viscosity.
He was the first to realise that the rate of flow (γ) is directly related to the applied stress (σ): the constant of proportionality is the coefficient of dynamic viscosity (η), more usually referred to as the viscosity.
Simple fluids which obey this relationship are referred to as Newtonian fluids and those which do not are known as non-Newtonian fluids.
The phenomenon of viscosity is best understood by a consideration of a hypothetical cube of fluid made up of infinitely thin layers (laminae) which are able to slide over one another like playing cards in a pack or deck When a force is applied to the uppermost layer, it is assumed that each subsequent layer will move at progressively decreasing velocity and that the bottom layer will be stationary
A velocity gradient will therefore exist, and this can be calculated by dividing the velocity of the upper layer by the height of the cube. The resultant gradient, which is effectively the rate of flow but is usually referred to as the rate of shear or shear rate, γ. The applied stress, known as the shear stress, σ, is derived by dividing the applied force by the area of the upper layer.
As Newton’s law can be expressed as σ = η γ then η= σ/γ
In summary, Newtonian fluids have a constant viscosity or flow, and that their flow behaviour only changes when there is a change in temperature or pressure. Stress does NOT affect this type of fluid.
With Newtonian fluids, the relationship between sheer stress and sheer rate is linear.
Newtonian fluids include water, air, alcohol, and glycerol.
Let’s look at WATER: Temperature affects its viscosity. At 0˚C it turns into a solid, and at 100˚C it is a gas, but between those temperatures is behaves like a normal fluid and has a constant viscosity.
The viscosity of water is NOT affected by applied stress.
Non-Newtonian fluids DO NOT follow Newton’s law of viscosity. In non-Newtonian fluids, the viscosity changes when under force/stress to either more liquid or more solid. In simple terms, if you apply a force to such fluids (say you hit, shake or jump on them), the sudden application of stress can cause them to get thicker and act like a solid, or in some cases it results in the opposite behaviour, and they may get runnier than they were before. Remove the stress (let them sit still or only move them slowly) and they will return to their earlier state.
Non-Newtonian fluids include some slat solutions, polymers and then more recognisable ketchup, cream, custard, blood and oobleck!
Sheer Stress and Sheer Rates
Ideal suspending agents should exhibit high viscosity at low shear rate (slow down the rate of sedimentation or remain suspended permanently on storage) and should have a low viscosity at high shear rate (i.e., it should be free flowing during shaking and pouring)
Flocculated system shows pseudoplastic or plastic behaviour under shear, also shows thixotropic behaviour.
Deflocculated systems exhibit Newtonian flow; however, may exhibits dilatancy if high conc of dispersed phase is used.
A suspending agent, which shows thixotropic and pseudoplastic behaviour, is useful because it forms a gel on standing (storage) and becomes fluid on shaking.
Rheology in Emulsions
Poloxamers (Pluronics) are excipients used as surfactants, solubilising agents and emulsifying agents. They form a clear gel in water (at low conc and low temp, Newtonian); however, at high conc and temp some poloxamers exhibit “sol-gel” form (non-Newtonian).
Polymer solutions as ophthalmic wetting solutions for contact lenses