Viscosity and Rheology PDF

10/5/2018 Viscosity and Rheology Hilda Amekyeh (PhD) UNIVERSITY OF HEALTH...

10/5/2018 Viscosity and Rheology Hilda Amekyeh (PhD) UNIVERSITY OF HEALTH AND ALLIED SCIENCES 1 School of Pharmacy Outline Introduction/Definitions Importance of studying rheology Newton’s law of flow Viscosity Types of flow Measurements of viscosity Pharmaceutical applications Recommended Reference Books Pharmaceutics: The Science of Dosage Form Design Martin’s Physical Pharmacy and Pharmaceutical Sciences Remington: Essentials of Pharmaceutics UNIVERSITY OF HEALTH 2 AND ALLIED SCIENCES School of Pharmacy 1  10/5/2018 Introduction/Definitions Rheology – Greek term coined by Eugene C. Bingham “rheo” means “to flow” “logos” is from the Greek word “logia”, which means “study of” Rheology is the study of the flow and deformation of matter under stress. UNIVERSITY OF HEALTH 3 AND ALLIED SCIENCES School of Pharmacy Deformation describes the change of matter in terms of shape and/or volume. Studying the flow properties of liquids is important for the pharmacist. For instance The flow behaviours of several dosage forms (e.g., suspensions, simple liquids, gels, creams, and pastes) usually change when exposed to different stress conditions during their manufacture. UNIVERSITY OF HEALTH 4 AND ALLIED SCIENCES School of Pharmacy 2  10/5/2018 Importance of Studying Rheology The rheological properties of pharmaceutical products can affect the following: Formulation of various dosage forms Drug absorption and bioavailability Patient acceptability of products and patient compliance. E.g., Stiff creams are difficult to use or could cause pain; hence, the patient might be reluctant to use such a product. Suspensions and emulsions should easily flow out of their bottles to allow for easy dosing. Toothpaste should be easily squeezed out of a tube, but should form a string without fluid leakage. UNIVERSITY OF HEALTH 5 AND ALLIED SCIENCES School of Pharmacy Passage of the liquid through a syringe needle Fluidity of solutions to be injected Tablet coating Choice of processing equipment during the manufacture of pharmaceuticals Mixing and flow of materials, their packaging into containers, their removal prior to use, and their pouring from the container UNIVERSITY OF HEALTH 6 AND ALLIED SCIENCES School of Pharmacy 3  10/5/2018 Proper understanding of rheology is essential for the development/preparation evaluation performance of pharmaceutical dosage forms. The ability of a material to flow depends on: its viscosity the magnitude of stress applied temperature its composition/molecular chain characteristics and arrangements UNIVERSITY OF HEALTH 7 AND ALLIED SCIENCES School of Pharmacy Viscosity The flow property of simple liquids is usually expressed in terms of viscosity. Viscosity of a fluid may be described as the resistance of the fluid to flow or movement. The higher the viscosity of a liquid is, the greater is its resistance to flow. E.g., castor oil, honey, and syrups resist flow more than water or alcohol does. UNIVERSITY OF HEALTH 8 AND ALLIED SCIENCES School of Pharmacy 4  10/5/2018 More viscous materials require larger amounts of energy during mixing. Viscosity can be modified to improve products. However, this must be done cautiously. E.g., Decreasing the viscosity of a suspension could increase the sedimentation rate of the solids suspended in it. Viscosity might be reduced by applying heat This can reduce mixing time and improve product homogeneity. However, some products may be destroyed if heated. UNIVERSITY OF HEALTH 9 AND ALLIED SCIENCES School of Pharmacy Viscosity Coefficients Dynamic viscosity Kinematic viscosity Relative viscosity Specific viscosity Intrinsic viscosity UNIVERSITY OF HEALTH 10 AND ALLIED SCIENCES School of Pharmacy 5  10/5/2018 Viscosity was quantitatively defined by Isaac Newton. He first realised that rate of flow (symbol, γ; unit, 1/s) is directly related to applied stress (symbol, τ or σ; unit, mPa). τ∝γ Rate of flow is also referred to as rate of shear. The constant of proportionality is the coefficient of dynamic viscosity (η; unit, Pascal-second (Pa·s)), more usually referred to as viscosity (absolute viscosity). i.e., τ = ηγ (Newton’s Law of Viscosity) The SI unit for η is Pascal-second (Pa·s) or Poise (P). 1 mPa·s is equivalent to 1 centipoise (cP) UNIVERSITY OF HEALTH 11 AND ALLIED SCIENCES School of Pharmacy The phenomenon of viscosity is best understood by considering the following. Let’s consider two parallel plates having a specific fluid (with height, H) between them. The liquid is made up of very thin layers. The bottom plate is fixed, while the top plate is moved to the right, dragging the fluid with it. The layer of fluid in contact with either plate does not move relative to the plate. Each layer exerts a force on the one below it, trying to drag it along. UNIVERSITY OF HEALTH 12 AND ALLIED SCIENCES School of Pharmacy 6  10/5/2018 It is assumed that each subsequent layer will move at progressively decreasing velocity. This produces a continuous variation in speed from v to 0. Care is taken to ensure that the flow is laminar; that is, the layers H do not mix. τ= ( ) = N/m2 ( ) / γ= = = s-1 ( ) UNIVERSITY OF HEALTH 13 AND ALLIED SCIENCES School of Pharmacy Viscosities of Some Fluids of Pharmaceutical Interest Fluid Dynamic Viscosity at 20 °C (cP) Chloroform 0.58 Water 1.002 Ethanol 1.20 Olive oil 84.0 Glycerol 1490 UNIVERSITY OF HEALTH 14 AND ALLIED SCIENCES School of Pharmacy 7  10/5/2018 Kinematic Viscosity Kinematic viscosity is another coefficient that can be used to characterise a fluid. Kinematic viscosity (v) is defined as dynamic viscosity (η) divided by the density of the fluid (ρ). η i.e., v = ρ Its SI unit is m2s-1 [or the Stoke (St). NB: 1 St = 10-4 m2 s-1 ] Kinematic viscosity is also referred to as momentum diffusivity of a fluid. UNIVERSITY OF HEALTH 15 AND ALLIED SCIENCES School of Pharmacy Relative and Specific Viscosities Relative viscosity (ηr) or viscosity ratio of a solution is the ratio of the solution’s viscosity (ηsol) to the viscosity of the solvent (ηs). i.e., ηr = ηsol ηs NB: Relative viscosity has no units. Specific viscosity (ηsp) = ηr - 1 UNIVERSITY OF HEALTH 16 AND ALLIED SCIENCES School of Pharmacy 8  10/5/2018 Intrinsic Viscosity A colloidal dispersion is a dispersion of finely divided, insoluble solid particles (disperse phase) with a mean particle diameter of up to 1 µm in a fluid (dispersion medium or continuous phase). E.g., aluminium hydroxide and magnesium hydroxide suspensions Einstein derived the following equation to be used to estimate the viscosity of a colloidal dispersion: ηsol = ηs(1 + 2.5Ø) where Ø is the volume fraction of the colloidal phase (the volume of the dispersed phase divided by the total volume of the dispersion) UNIVERSITY OF HEALTH 17 AND ALLIED SCIENCES School of Pharmacy ηsol = ηs(1 + 2.5Ø) η ηs s = 1 + 2.5Ø (but = ηr ) ηs ηs ηr = 1 + 2.5Ø ηr − 1 = 2.5Ø (but ηsp = ηr - 1) ηsp = 2.5Ø η sp = 2.5 Ø NB: The volume fraction (Ø) is directly related to concentration (C) η Csp = k η sp is referred to as viscosity number or reduced viscosity C UNIVERSITY OF HEALTH 18 AND ALLIED SCIENCES School of Pharmacy 9  10/5/2018 η A plot of Csp as a function of concentration gives a linear relationship. ηsp C [η] Concentration (g/dL) The intercept produced on extrapolation of the line to the y-axis will yield the constant referred to as limiting viscosity number or intrinsic viscosity [η]. The unit for [η] is dL/g, which is also known as inverse concentration. UNIVERSITY OF HEALTH 19 AND ALLIED SCIENCES School of Pharmacy Types of Flow Systems UNIVERSITY OF HEALTH 20 AND ALLIED SCIENCES School of Pharmacy 10  10/5/2018 Newtonian Newtonian fluids are simple fluids. They obey Newton’s law of viscosity (τ = ηγ) Non-Newtonian This includes the following: Plastic Pseudoplastic Dilatant UNIVERSITY OF HEALTH 21 AND ALLIED SCIENCES School of Pharmacy When a Newtonian fluid is subjected to increasing rate of shear (γ), a plot of γ against the corresponding shear stress (τ) will produce a linear relationship. 𝟏 Slope = Shear rate η Shear stress Such a plot is referred to as a flow curve or rheogram. The slope of this plot gives the viscosity of the fluid. UNIVERSITY OF HEALTH 22 AND ALLIED SCIENCES School of Pharmacy 11  10/5/2018 Non-Newtonian Flow Most pharmaceutical fluids do not follow Newton’s law because their viscosities vary as shear stress is varied. The reason for this deviation is that such fluids are not simple fluids such as water and syrup. They are usually disperse or colloidal systems such as emulsions, suspensions, and gels. These materials are known as non-Newtonian fluids. UNIVERSITY OF HEALTH 23 AND ALLIED SCIENCES School of Pharmacy Plastic Flow Plastic flow is exhibited by concentrated suspensions, particularly if the continuous phase is of high viscosity or if the particles are flocculated. A plastic material does not flow until a certain value of shear stress (yield value) sufficient to overcome the van der Waals forces of attraction in the fluid is exceeded. The yield value is an indication of the degree of flocculation The more flocculated the suspension is, the higher the yield value will be. UNIVERSITY OF HEALTH 24 AND ALLIED SCIENCES School of Pharmacy 12  10/5/2018 Slope of linear curve = Mobility Shear rate Reciprocal of mobility = Plastic viscosity yield value Shear stress The yield value is obtained by extrapolating the linear portion of the curve to the shear stress axis. In practice, flow occurs at a lower shear stress than yield value. A plastic system resembles a Newtonian system at shear stresses greater than the yield value. UNIVERSITY OF HEALTH 25 AND ALLIED SCIENCES School of Pharmacy Pseudoplastic Flow Pseudoplastic materials flow as soon as shear stress is applied. Their viscosities decrease as shear rate is increased. They are referred to as “shear thinning” systems. No single value of viscosity can be used to characterise such fluids. Materials that exhibit this type of flow include aqueous dispersions of natural and chemically modified hydrocolloids or gums E.g., acacia, tragacanth, methylcellulose and carmellose, and synthetic polymers such as polyvinylpyrrolidone and polyacrylic acid. UNIVERSITY OF HEALTH 26 AND ALLIED SCIENCES School of Pharmacy 13  10/5/2018 The presence of long, high-molecular-weight molecules in solution results in entanglement together with the association of immobilised solvent. Under the influence of shear, the molecules tend to become disentangled and align themselves in the direction of flow. They thus offer less resistance to flow and this, together with the release of some of the entrapped water, accounts for the lower viscosity. UNIVERSITY OF HEALTH 27 AND ALLIED SCIENCES School of Pharmacy Shear rate Shear stress At higher shear stresses, the flow curve tends towards linearity, indicating that a minimum viscosity has been attained. This indicates that the orientation of the molecules is complete. The solution may then show a Newtonian flow at high shear stresses. UNIVERSITY OF HEALTH 28 AND ALLIED SCIENCES School of Pharmacy 14  10/5/2018 Dilatant Flow This type of flow is the opposite of pseudoplasticity. The viscosity of a dilatant material increases with increase in shear rate. Such materials increase in volume during shearing. They exhibit “shear thickening”. When the stress is removed, a dilatant system returns to its original state of fluidity. This type of behaviour is less common than plastic or pseudoplastic flow. It may be exhibited by dispersions containing a high concentration (≈ 50%) of small, deflocculated particles. UNIVERSITY OF HEALTH 29 AND ALLIED SCIENCES School of Pharmacy Under conditions of zero shear the particles are closely packed interparticulate voids are minimum particles are well lubricated by the dispersion medium At low shear rates, e.g., during pouring, fluid in the interparticulate voids can adequately lubricate the particles to ensure flow. As shear rate is increased, the particles come together this results in the creation of larger voids the vehicle drains into these voids consequently, the particles become less lubricated resistance to flow increases and viscosity increases UNIVERSITY OF HEALTH 30 AND ALLIED SCIENCES School of Pharmacy 15  10/5/2018 Resting state Sheared state Pharmaceutics: the design and manufacture of medicines The effect is progressive with increase in shear rate until eventually the material may appear paste-like as flow ceases. Fortunately, the effect is reversible and removal of the shear stress results in the re-establishment of the fluid nature. UNIVERSITY OF HEALTH 31 AND ALLIED SCIENCES School of Pharmacy Shear rate Shear stress During the processing of a material that exhibits dilatant flow High shearing (e.g., with high-speed blenders and mills) must be avoided. If the material becomes dilatant during processing, the resultant solidification could overload and damage the equipment. UNIVERSITY OF HEALTH 32 AND ALLIED SCIENCES School of Pharmacy 16  10/5/2018 Thixotropy Thixotropy is the property of some non-Newtonian fluids (specifically shear-thinning systems) to show a time-dependent change in viscosity. This occurs because the material experiences some structural breakdown when subjected to an increasing rate of shear. Thixotropy is defined as isothermal and comparatively slow recovery on standing of material that has lost its consistency through shearing. The common feature of all thixotropic materials is that if they are subjected to gradually increasing shear rate, followed immediately by decreasing shear rate to zero, then the down-curve will be displaced to the left of the up-curve (for τ – x-axis, γ – y-axis). As a result, the rheogram will exhibit a hysteresis loop UNIVERSITY OF HEALTH 33 AND ALLIED SCIENCES School of Pharmacy Plastic Pseudoplastic hysteresis loop Shear rate Shear rate up-curve Shear stress Shear stress UNIVERSITY OF HEALTH 34 AND ALLIED SCIENCES School of Pharmacy 17  10/5/2018 The presence of the hysteresis loop indicates that a breakdown in structure has occurred. The area within the loop may be used as an index of the degree of breakdown. A thixotropic suspension settles slowly after being agitated, which allows for accurate dosing, whereas a non-thixotropic one settles rapidly. Several gel and colloidal preparations exhibit thixotropy. UNIVERSITY OF HEALTH 35 AND ALLIED SCIENCES School of Pharmacy Measurement of Viscosity UNIVERSITY OF HEALTH 36 AND ALLIED SCIENCES School of Pharmacy 18  10/5/2018 The instrument used to measure the viscosity of a fluid is called a viscometer or viscosimeter. The following instruments can be used to estimate viscosity: Capillary viscometers Ostwald U-tube viscometer Newtonian fluids Suspended-level viscometer Falling-sphere viscometers Rotational viscometers UNIVERSITY OF HEALTH 37 AND ALLIED SCIENCES School of Pharmacy V W Ostwald U-tube Viscometer The liquid is introduced into the viscometer up to mark G through arm V using a long pipette. E The viscometer is then clamped vertically in a constant- C temperature water bath and allowed to reach the required temperature. F The level of the liquid is adjusted and is then blown or sucked into tube W until the meniscus is just above mark E. G The time for the meniscus to fall from mark E to mark F is then recorded. Capillary Determinations should be repeated until three readings within 0.5 s are obtained. Care should be taken not to introduce air bubbles partially occlude the capillary with small particles. UNIVERSITY OF HEALTH 38 AND ALLIED SCIENCES School of Pharmacy 19  10/5/2018 V W Z Suspended-level Viscometer A volume of liquid sufficient to fill bulb C is introduced via tube V. E The viscometer is clamped vertically in a constant- C temperature water bath and allowed to attain the F required temperature. Tube Z is closed and fluid is drawn into bulb C by the application of suction through tube W until the meniscus is just above the mark E. Tube W is then closed and tube Z opened so that liquid can be drawn away from the bottom of the capillary. Tube W is then opened and the time the fluid takes to fall between marks E and F is recorded. Determinations should be repeated until three readings UNIVERSITY OF HEALTH 39 within 0.5 s are obtained. AND ALLIED SCIENCES School of Pharmacy Calculation Of Viscosity from Capillary Viscometers Poiseuille’s law states that for a liquid flowing through a capillary tube, 𝜫𝒓𝟒𝒕𝑷 η= 𝟖𝑳𝑽 r - radius of the capillary t - time of flow P - pressure difference across the ends of the tube L - length of the capillary V - volume of liquid flowing through the tube As the radius and length of the capillary, and the volume are constant for a given viscometer, then η = KtP UNIVERSITY OF HEALTH 40 AND ALLIED SCIENCES School of Pharmacy 20  10/5/2018 The pressure difference (P) depends upon the density (ρ) of the liquid, the acceleration due to gravity (g), and the difference in heights of the two menisci in the two arms of the viscometer. Because the value of g and the level of the liquids are constant, these can be included in a constant and can be written for the viscosities of an unknown and a standard liquid. η = Ktρ …… eqn X Therefore, considering the viscosities of a standard liquid (1) and an unknown liquid (2), eqn X can be written as UNIVERSITY OF HEALTH 41 AND ALLIED SCIENCES School of Pharmacy η1 η1 = Kt1ρ1 for liquid 1 (K = ) t1 ρ 1 η2 η2 = Kt2ρ2 for liquid 2 (K = ) t2ρ2 η1 η 𝜼 = 2 (but v = ) t1ρ1 t2ρ2 ρ 𝒗1 𝒗2 = ……. eqn Y t1 t2 UNIVERSITY OF HEALTH 42 AND ALLIED SCIENCES School of Pharmacy 21  10/5/2018 V1 and V2 are the kinematic viscosities of the reference and test liquids, respectively, and t1 and t2 are their respective flow times. Water is normally used as the reference liquid. The eqn Y can be rearranged as V2 = V1 (t2 /t1) UNIVERSITY OF HEALTH 43 AND ALLIED SCIENCES School of Pharmacy Falling-Sphere Viscometer This viscometer is based on Stokes’ law. When a body falls through a viscous medium, it experiences a resistance or viscous drag which opposes the downward motion. This type of viscometer is only of use for Newtonian fluids. This instrument can only be used after calibration with standard fluids. UNIVERSITY OF HEALTH 44 AND ALLIED SCIENCES School of Pharmacy 22  10/5/2018 Sphere The liquid is placed in the fall tube, which is clamped vertically in a constant-temperature bath. Guide tube Sufficient time is allowed for temperature equilibration to occur and for air bubbles to rise to the surface. Fall A tube A clean steel sphere at the temperature of the experiment is introduced into the fall tube through a narrow guide tube. The time taken for the sphere to fall between marks A and B is recorded. B The average of three readings (all within 0.5%) is calculated. UNIVERSITY OF HEALTH 45 AND ALLIED SCIENCES School of Pharmacy The equation used for calculations (based on Stokes’ law) ρs 𝒗 = 𝑲𝒕 ρl - 1 v = Kinematic viscosity of the liquid K = A constant that can be determined by testing a liquid with known kinematic viscosity t = Time taken for the sphere to fall between the marks ρs = Density of the sphere ρl = Density of the liquid UNIVERSITY OF HEALTH 46 AND ALLIED SCIENCES School of Pharmacy 23  10/5/2018 Rotational Viscometers (Rheometers) These instruments rely on the viscous drag exerted on a body when it is rotated in a fluid to determine the viscosity of the fluid. The major advantage of these instruments is that several shear rates can be achieved. For modern instruments, a programme of shear rates can be produced automatically. The flow curve of the study material can be obtained directly. UNIVERSITY OF HEALTH 47 AND ALLIED SCIENCES School of Pharmacy Suitable for testing transparent and opaque samples Viscosity coefficient determined is dynamic viscosity They are used when exact shear rates and shear stresses are required. The Stormer viscometer is a type of rotational viscometer. The viscosity of a fluid is determined by measuring the time taken for an inner cylinder to perform a fixed number of revolutions in response to a particular weight. The viscometer is calibrated using varying weights and fluids of accurately known viscosities. UNIVERSITY OF HEALTH 48 AND ALLIED SCIENCES School of Pharmacy 24  10/5/2018 Thomas-Stormer Viscometer Brookfield Viscometer UNIVERSITY OF HEALTH 49 AND ALLIED SCIENCES School of Pharmacy Winding Revolution spool counter Pulley Brake Bob Weight Cup Constant temperature water bath UNIVERSITY OF HEALTH 50 AND ALLIED SCIENCES School of Pharmacy 25  10/5/2018 Loading Weight T1 T2 Taverag Shear rate (g) e (rev/s) 5 10 15 20 25 Unloading Weight T1 T2 Taverag Shear rate (g) e (rev/s) 25 20 15 10 5 UNIVERSITY OF HEALTH 51 AND ALLIED SCIENCES School of Pharmacy Applications of Rheology in Pharmaceutical Formulations UNIVERSITY OF HEALTH 52 AND ALLIED SCIENCES School of Pharmacy 26  10/5/2018 Drug Absorption and Bioavailability Viscosity affects drug absorption from the site of administration. E.g., the viscosities of creams and lotions may affect the rate of drug absorption through the skin Higher drug release is generally possible from softer, less viscous bases. The viscosity of the base affects the rate of diffusion of the active ingredients. Bioavailability is the relative amount of an administered dose of a drug that reaches systemic circulation intact and the rate at which this occurs. It is the rate and extent of drug absorption. However, drug dissolution precedes absorption. UNIVERSITY OF HEALTH 53 AND ALLIED SCIENCES School of Pharmacy The rate of dissolution of a drug particle decreases as the viscosity of its dissolution medium increases. In the case of depot injections, prolonged drug delivery from a particular site in the body is often desired. The preparation should be easily injected to the site of administration. A high yield value and fast thixotropic recovery after injection are needed for the drug to remain localised. A proper understanding of the rheological behaviour of a formulation (and if possible that of the fluid at the absorption site) is essential in the evaluation of drug bioavailability. UNIVERSITY OF HEALTH 54 AND ALLIED SCIENCES School of Pharmacy 27  10/5/2018 Suspensions The rheological properties of suspensions are markedly affected by the degree of flocculation. This is because the amount of free continuous phase is reduced in flocculation, as it becomes entrapped in the diffuse floccules. Consequently, the viscosity of a flocculated suspension is normally higher than that of its deflocculated form. When a disperse system is highly flocculated, then there is the possibility of interactions occurring between floccules. This may result in the formation of a structured system. UNIVERSITY OF HEALTH 55 AND ALLIED SCIENCES School of Pharmacy If the forces bonding floccules together are capable of withstanding weak stresses then a yield value will result, and below this value the suspension will behave like a solid. Once the yield value is exceeded, structural breakdown increases with increasing shear stress. Therefore, flocculated suspensions exhibit plastic or, more commonly, pseudoplastic behaviour. If the breakdown and reformation of the bonds between floccules is time-dependent, then thixotropy will also be observed. UNIVERSITY OF HEALTH 56 AND ALLIED SCIENCES School of Pharmacy 28  10/5/2018 The formation of structures does not occur in deflocculated suspensions. Therefore, the rheological behaviour of deflocculated suspensions is determined by that of the continuous phase. As the suspension becomes more concentrated and the particles come into contact, then dilatancy will occur. In general suspensions should be formulated so that the product is easily administered (e.g. easily poured from a bottle or forced through a syringe needle) sedimentation is either prevented or retarded; if it does occur, redispersion is easy the product has an elegant appearance UNIVERSITY OF HEALTH 57 AND ALLIED SCIENCES School of Pharmacy Deflocculated Particles in Newtonian Vehicles When such systems sediment, a compact sediment or cake is produced which is difficult to redisperse. Sedimentation rate can be reduced by increasing the viscosity of the continuous medium, which will remain Newtonian. However, this should be done cautiously to ensure easy pouring of the suspension from a bottle. Moreover, if sedimentation does occur, then subsequent redispersion may be even more difficult. UNIVERSITY OF HEALTH 58 AND ALLIED SCIENCES School of Pharmacy 29  10/5/2018 Deflocculated Particles in Non-Newtonian Vehicles Pseudoplastic/plastic media can be used in the formulation of suspensions, as they retard the sedimentation of small particles. Hydrocolloids used as suspending agents impart non-Newtonian properties, normally pseudoplasticity, to the suspensions. The 3-D gel network formed by suspending agents traps deflocculated particles at rest and retards or prevents sedimentation. Shaking and pouring (high stress) are facilitated as the medium undergoes structural breakdown and the gel network is destroyed. UNIVERSITY OF HEALTH 59 AND ALLIED SCIENCES School of Pharmacy Flocculated Particles In Newtonian Vehicles Such particles will sediment on standing. Because the aggregates are diffuse, a large volume of sediment is produced, which is easy to redisperse. Such products may appear inelegant since the sediment does not fill the whole fluid. In Non-Newtonian Vehicles These systems have the combined advantages of flocculated particles and non-Newtonian dispersion media. UNIVERSITY OF HEALTH 60 AND ALLIED SCIENCES School of Pharmacy 30  10/5/2018 Emulsions Most medicinal emulsions, except very dilute ones, exhibit non-Newtonian behaviour. Fluid emulsions are usually pseudoplastic, whereas semisolid ones exhibit plastic flow and may have high yield values. Shear thinning formulations make good topical products, whereas dilatant topical preparations may not be desirable. Several pharmaceutical products can be formulated by altering the concentration of the disperse phase and the nature and concentration of the emulsifying agent. UNIVERSITY OF HEALTH 61 AND ALLIED SCIENCES School of Pharmacy Thixotropy Thixotropy is useful in the formulation of pharmaceutical suspensions and emulsions. Suspensions and emulsions must be poured easily from their containers. A thixotropic suspension settles slowly after being agitated, which allows for accurate dosing, whereas a non-thixotropic suspension settles rapidly. UNIVERSITY OF HEALTH 62 AND ALLIED SCIENCES School of Pharmacy 31  10/5/2018 Issues with low-viscosity suspensions and emulsions Rapid settling of solid particles in suspensions and rapid creaming of emulsions Creaming in emulsions can result in coalescence Solid particles that have settled can stick together, producing sediment that is difficult to redisperse (caking/claying) UNIVERSITY OF HEALTH 63 AND ALLIED SCIENCES School of Pharmacy A thixotropic agent (e.g., bentonite, colloidal silicon dioxide) can be added to such suspensions or emulsions to confer a high viscosity or yield value. A high viscosity will retard sedimentation and creaming. A yield value will prevent them altogether, since there is no flow below yield stress. In order to pour the suspension or emulsion from its container: shaking must be done at shear stresses above the yield value. Back on the shelf, the viscosity slowly increases again and the yield value is restored. UNIVERSITY OF HEALTH 64 AND ALLIED SCIENCES School of Pharmacy 32  10/5/2018 Considerations During Manufacturing and Product Usage During the processing/usage of a dilatant material High shearing/mixing (e.g., with high-speed blenders and mills) must be avoided. If the material becomes dilatant during processing, the resultant solidification could overload and damage the equipment. Similarly, such materials should not be passed through tubes at high speed. They may thicken, build up pressure, and burst the tubes. UNIVERSITY OF HEALTH 65 AND ALLIED SCIENCES School of Pharmacy Choice of Packaging Materials During packaging, the rheologicial property of a material has to be fully considered. Highly viscous preparations, e.g., ointments and pastes, are usually packaged in wide-mouthed containers/jars to facilitate easy removal for use. Conversely, less viscous or liquid preparations are usually packaged in containers with narrow openings, e.g., bottles, to reduce spillage. UNIVERSITY OF HEALTH 66 AND ALLIED SCIENCES School of Pharmacy 33  10/5/2018 END OF LECTURE UNIVERSITY OF HEALTH 67 AND ALLIED SCIENCES School of Pharmacy 34