Rheology

Rheology Rheology is the branch of physics which deals with deformation and flow of matter. The term rheology, from Greek rheo (to flow) and logy (science). This term was used to describe the flow of liquids and the deformation of solids.

Rheology Viscosity : is an expression of the resistance of a fluid to flow; the higher the viscosity, the greater the resistance.

Rheology may be defined as the science that concerned with the deformation of matter under the influence of stress, which may be applied perpendicularly to the surface of a body (tensile stress), tangentially to the surface of a body (shearing stress), or at any other angle to the surface of the body.

There are two extremes of rheological behavior: Most viscoelastic materials lie between elastic and viscous behavior. i) Elastic behavior—which refers to the ability of a formulation to restore its original shape when the external force is removed. It is a spontaneous and reversible deformation. Exhibited by elastic bodies. ii) Viscous (or plastic) behavior, which is known as a property of ideal Newtonian liquids, where any deformation ceases when the applied force is removed. It is a permanent or irreversible deformation. Plastic deformation is exhibited by viscous bodies.

Rheology is important in pharmaceutical science. The flow properties influence each step of the pharmaceutical development processes, such as: Filling. Mixing. Packing. Removal of a substance from the container, extrusion from a tube, or passage through a syringe needle.

The rheology of a particular product (which can range in consistency from fluid to semisolid to solid) can affect: patient acceptability of the product. physical stability of the product biological availability of the product .

NEWTONIAN’S LOW OF FLOW Let us consider a block of liquid consisting of parallel plates of molecules as shown in the figure (1). The bottom layer is considered to be fixed in place. If the top plane of liquid is moved at constant velocity, each lower layer will move with a velocity directly proportional to its distance from the stationary bottom layer Figure (1): Representation of shearing force acting on a block of material

Rate of Shear, G = dv/dr It is the velocity difference dv between two planes of liquid separated by an infinite distance dr. It is Indicates how fast a liquid flows when a stress is applied on it.   The Shearing Stress, F =F'/A It is the force per unit area required to cause flow.

Rheogram The graph representing the flow property of a material is termed as Rheogram. To express the rheological properties of liquids graphs showing the variation of shear rate with shear stress (obtained by plotting shear rate, G, versus shear stress, F)   Assessment of Rheological Property of Materials There are a number of ways to quantify the thixotropic behaviour of materials. Among these methods, viscometers or rheometers is considered one of the best instruments used to assess rheological behaviour at varying shear stress and shear rates.

Classification of Systems A system is considered as either a Newtonian flow or non-Newtonian flow depending on whether viscosity is correlated with the shear rate or not.

Classification of Systems The liquids that follow Newtonian flow include water, ethanol, benzene, ethyl ether, glycerin and castor oil. Whereas the liquids that follow non-Newtonian flow include ointments, creams, gels, pastes, and clays.

Newtonian systems A system is said to have Newtonian flow behavior when its viscosity is independent of shear rate and dependent upon the composition of the liquid, temperature and pressure. It is observed that viscosity decreases as the temperature increases, whereas it increases with an increase in pressure.

The graphs representing the flow properties are termed as Rheograms. In case of Newtonian system the flow curve (shear stress vs. shear rate) is straight line passing through origin, indicating that shear stress (τ) or the force per unit area (F/A) varies directly with the shear rate as described in the following equations.

Newton recognized that: The higher the viscosity of a liquid, the greater the force per unit area (shearing stress) required to produce a certain rate of shear.Thus, the rate of shear is directly proportional to the shearing stress. F'/A α dv/dr F'/A = η dv/dr ……..(1)  where η is a constant known as Viscosity η = F / G…………...(2)  F = η G………..(3)   The slope of the line represents viscosity, which is defined as the resistance to the relative motion of adjacent liquid layers.

The unit of viscosity is poise or dyne.sec.cm-2.   Poise Is the shearing force required to produce a velocity of 1 cm/sec between two parallel planes of liquid each 1 cm2 in area and separated by a distance of 1 cm. Centipoise (cp) = 0.01 Poise. Newtonian systems like water, simple organic liquids, true solutions and dilute suspensions and emulsionssolutions and dilute suspensions and emulsions

2. Non-Newtonian systems As the name implies, there is a deviation from Newton's relation between shear stress and the rate of shear. The viscosity of non-Newtonian fluids changes according to the rate of shear, thus non-Newtonian systems have no constant viscosity. non-Newtonian systems can be of three general types, such as plastic, pseudo plastic and dilatants.

In case of plastic materials, it is observed that there is no flow until it reaches the yield value as shown in the following figure: When stress above the yield value is applied, they exhibit free flowing liquid nature. Materials exhibiting this type of flow property are also termed as Bingham Bodies.

Dilatant systems (also called as shear thickening agent) are systems whose viscosity increases with an increase in the rate of shear, as shown in the following Figure: This property is exhibited by dispersions containing high percentage of small, deflocculated particles, for example: clays, slurries, suspensions of starch in water, aqueous glycerine or ethylene glycol.

Fig.  Effect of shear rate on the viscosity of (A) Newtonian liquids, (B) shear-thinning systems and (C) shear thickening

The viscosity of the fluid varies with the shear stress and the consistency depends upon: The rate of shear. The duration of shear (Time)

Time dependant behaviour Thixotropy is a term to describe an isothermal system in which the apparent viscosity decreases under shear stress, followed by a gradual recovery when the stress is removed. The opposite of thixotropic materials are rheopectic materials which are materials that become more viscous as the duration of applied force increases. Thixotropy and rheopexy profiles (viscosity vs. time).

Because of the wide range applications of the thixotropic properties in the field of pharmacy, formulations in particular, it is essential to understand this complex phenomenon utilized in the advanced formulations.

The factors affecting thixotropic property The phenomenon of thixotropy is influenced by several factors like pH, temperature, polymer concentrations, polymer modification or combinations, addition of cations or anions and excipients, such as lecithin, sodium chloride and glycerol.

pH Due to wide variations in the pH value of the physiological fluids, solution to gel (sol–gel) conversion induced by pH changes seems to be an ideal approach for enhancement of the pharmacological efficacies of the topical drug delivery, especially ophthalmic and intravaginal applications.

pH One of the most widely used polymers with thixotropical property is polyacrylic acid (PAA) (Carbopol polymers), whose aqueous solutions were less viscouse and acidic in nature, and were transformed into gels upon increasing the pH.

2. Temperature Thermo-reversible gels can be used as a delivery system which requires a sol–gel transition at body temperature. For example, the viscosity of Poloxamer-407 (Pluronic F127) is increased with temperature. Poloxamers (Pluronics) are hydrophilic non-ionic polymeric surfactant (triblock copolymer) consisting of a central hydrophobic block of polypropylene glycol flanked by two hydrophilic blocks of polyethylene glycol.

3. Concentrations of the polymer(s) The Poloxamer based system developed for the ophthalmic drug delivery showed the strong concentration dependence of sol–gel–sol conversion. A rheological property of binary hydroalcoholic gels made of Carbopol and hyaluronic acid varied as a function of the polymer concentration.

4. Polymer combinations An aqueous mixture of 1.5% HPMC and 0.3% PAA exhibited the rheological characteristics that were similar to those of 2.0% PAA solution.

5. Addition of cat/anions An addition of cat/anions significantly affected the viscosity of the thixotropic formulations. An incorporation of positively charged ions, such as Ca++, into sodium alginate (SA) dispersions enhanced the viscosity and shifted the flow type from Newtonian to a pseudo plastic flow with thixotropic properties.

6. Addition of excipients An addition of excipients, such as lecithin, sodium chloride and glycerol, to the gel system significantly affected its viscosity, producing viscous thixotropic gels with enhanced stability of the system. Lecithin, a permeation enhancer, induced sol–gel conversions of Poloxamer 407 gels through the formation of micellar structures and affected in vitro permeation rate of triamcinolone acetonide.

Pharmaceutical applications of thixotropy The time-dependent change in viscous nature of thixotropy finds its major applications in pharmaceutical formulations including: Hydrogel, Ointment, Suspensions, and Emulsions. Through various routes including: Oral, Topical, Ophthalmic, and Mucosal administration.

1. Ophthalmic formulations The conventional ocular drug delivery systems like solutions, suspensions and ointments showed drawbacks, such as Increased pre-corneal elimination, High variability in efficiency Blurred vision. Various formulations including gels and nanoparticles with thixotropic property have been developed as an ophthalmic drug delivery system to address these drawbacks.

It was reported that aqueous PAA gels administered into rabbit eyes could be retained for 4–6 h and resulted in a longer duration and greater activity of incorporated pilocarpine compared with viscous drug solutions.

2. Parenteral formulations It is of strong interest for biomedical field to develop a hydrogel which is able to pass through a needle without losing its structure. An ideal thixotropic liquid should have high consistency under the storage conditions yet being removed easily.

2. Parenteral formulations In one study, 50% hydrogels made of hyaluronane and alginate were formulated, their thixotrophic behavior was verified, and their mechanical properties were determined before and after the passage through the needle. The unique property of these gels to flow like a liquid with thixotropic behavior allowed them to be used as an injectable hydrogel drug delivery system for various bioactive agents (drugs, proteins, vaccines or plasmid DNAs).

3. Nasal formulations The major limiting factor for drug delivery to the nasal mucosa has been the mucociliary clearance. It was reported that thixotropic solutions containing methylcellulose derivatives lowered the clearance rate and enhanced the bioavailability of the drugs administered through the nose.