Thixotropy & Rheology in Pharmacy PDF

Time dependant behavior (Thixotropy) ▪ Non-Newtonian systems such as plastic, pseudoplastic and dilatant systems at a given temperature show time dependent change in viscosity at varying shearing stresses. 1. Thixotropy in plastic and pseudoplastic systems; ▪ In shear-thinning systems, when...

Time dependant behavior (Thixotropy) ▪ Non-Newtonian systems such as plastic, pseudoplastic and dilatant systems at a given temperature show time dependent change in viscosity at varying shearing stresses. 1. Thixotropy in plastic and pseudoplastic systems; ▪ In shear-thinning systems, when removing the shearing stress, the viscosity is regained after some time. this behaviour is described by thixotropy. ▪ Thixotropy is described by a reversible isothermal transformation from gel-sol-gel. ▪ Rheogram of such systems show a hysteresis where, as the shearing stress is increased an up-curve is obtained, on reducing the shear stress gradually, a down curve shifted to the left side is obtained. Pseudoplastic Shear rate Shear stress plastic Explanation of thixotropy in plastic and pseudo plastic materials ▪ Thixotropic systems contain asymmetric particles which set up a loose three dimensional structure which is rigid and resembles a gel. As shear is applied, the structure breaks down and the material changes from gel to sol structure. On removing the applied stress, the material reform its original structure of gel state. Applied stress Removing stress ▪ E.g., for plastic systems showing thixotropy; bentonite and petrolatum ▪ E.g., for pseudplastic systems showing thixotropy; dispersion of synthetic suspension agents  Thixotropy and Suspension Formulation ▪ Thixotropy is particularly useful in suspensions and emulsions. Where, pharmaceutical suspensions and emulsions must be poured easily from containers, therefore; low viscosity of these preparations is required. However, the low viscosity causes rapid settling of solid particles in suspensions and rapid creaming of emulsions. ▪ A thixotropic agent such as microcrystalline cellulose is incorporated into the suspensions or emulsions to give a high viscosity that retard sedimentation and creaming. When it is desired to pour some of the suspension or emulsion from its container, shaking of the container will reduce the viscosity and thereby the preparation may be poured easily. Thixotropy in dilatant systems ▪ E.g. quicksand (Clay and water) Rheogram of thixotropy in dilatant systems Irreversible thixotropy ▪ Application of shearing stress on a gel form, will break down the gel structure to sol form, which on removal of the stress, the sol form will never changed back into the original gel form. ▪ E.g. gels produced from high molecular weight polysaccharides Rheopexy ▪ The process of reforming of the gel structure after it has been deformed can be accelerated by applying gentle and regular movements (rolling or rocking motion). ▪ The regular motion facilitates the random structure of the gel form. Determination of Rheological properties ▪ Successful determination of viscosity depends on the choice of the correct instrument. ▪ For Newtonian system; ▪ Instruments that operate at a single rate of shear such as capillary viscometers can be used. ▪ For non-Newtonian systems ▪ Instruments that can operate at different rates of shear are required. ▪ The various viscometers can be broadly divided into the following types: ▪ 1. Capillary Instruments. ▪ 2. Falling and Rising body Apparatus. ▪ 3. Rotational Viscometers.  1. Capillary Viscometers ▪ Capillary Viscometers are very accurate for the measurement of viscosity of Newtonian fluids having low viscosity. ▪ The time for the fluid to flow by gravity from one mark in a capillary column to the second mark is measured. e.g., The Ostwald’s U-tube viscometer. ▪ Used to determine the relative viscosity to water η1 / η2 = t1 ρ 1 / t2 ρ2 ▪ Where ▪ η1 = sample viscosity ▪ η2 = water viscosity ▪ t1 = flow time of sample ▪ t2 = flow time of water ▪ ρ 1 = density of sample ▪ ρ 2 =density of water  2. Falling and Rising Body Apparatus ▪ Falling Sphere viscometer; ▪ The principle of this instrument is based on Stokes’ law which states that when a body falls through a viscous medium, it experiences a resistance which opposes the motion of the body. ▪ Stokes’ law η = d2g (ρs – ρl)/18 v ▪ Where ▪ η = viscosity ▪ d = the diameter of the sphere ▪ g = Gravity factor ▪ v =Velocity ▪ ρs = the density of the sphere ▪ ρl = Density of the liquid 3. Rotational Viscometers ▪ Rotation Viscometers: use the idea that; (the torque required to turn an object in a fluid, can indicate the viscosity of that fluid). ▪ They do so by measuring the required torque for rotating a disk or bob in a fluid at known speed. ▪ Advantage: A wide range of shear rate can be achieved using these instruments ▪ Commercially available rotational viscometer 1. Cub and Bob Viscometer 2. Cone and plate viscometer 1. Cup and Bob Viscometer ▪ It consists of two coaxial cylinders of different diameters. The outer cylinder forms the cup into which the inner cylinder or the bob is fixed centrally. ▪ The sample to be analyzed is sheared in the space between the outer wall of the bob and the inner wall of the cup. ▪ There are two classical geometries in "cup and bob" viscometers, known as; ▪ "Couette type viscometer" ‘the cup is rotated’ ▪ "Searle type viscometer" ‘the bob is rotated’ ▪ E.g., Brookfield viscometer ▪ Disadvantages of Cup and Bob Viscometer ▪ If the gap between the cup and bob is large, shearing of the sample will not be uniform. ▪ Fractional heat may develop at high rate of shear. ▪ Difficult filling and cleaning ▪ Relatively large quantity of the material to be analyzed is required. ▪ 2. Cone and plate viscometer ▪ The cone is driven by a speed motor and the sample is sheared in the narrow gap between the stationary plate and the rotating con ▪ Viscosity =C (T/V) ▪ Where C = instrument constant ▪ T = torque ▪ V= velocity (shear rate) ▪ Advantages over cup and bob viscometer ▪ Time saved in cleaning ▪ The small sample size ▪ More suitable for semisolid preparations ▪ Rate of shear is constant throughout the sample Application of Rheology in pharmacy ▪ Rheology of Emulsions ▪ Most emulsion systems (lotions & creams) are non- Newtonian. ▪ Fluid emulsions (lotions) are pseudoplastic. ▪ Semisolid emulsions (creams) are plastic and exhibit marked yield values. ▪ Proper rheological characteristics are important for stability of emulsified systems (Avoid creaming, coalescence and breaking of emulsions). ▪ Rheology of Suspensions ▪ Most of the Pharmaceutical suspensions exhibit plastic or pseudoplastic behaviour. ▪ Proper selection of the rheological characteristics may improve the physical stability of the suspension (avoid problems like; settling, caking and particle growth). ▪ Rheology of ointments and gels ▪ Most of the topical semisolid show plastic flow. ▪ Some pastes exhibit dilatancy when subjected to high shear ▪ The rheological characteristics of gels and ointments affect extrudability, adherence and spreading of the product on the skin. Rheology and pharmaceutical processing ▪ Rheology plays an important role in formulation processes e.g.; ▪ In mixing ▪ Shear thinning system require a large impellers operating at low speed for good mixing. ▪ Dilatant system should be processed with low shear mixer to prevent increasing the viscosity. ▪ Low shear mixing is required in certain polymeric dispersion to prevent the breakdown of the structure due to de-polymerization due to the high shearing. ▪ In packaging into containers