Dosage Forms I PDF Spring 2024-2025

9/15/2024 Dosage Forms I M. Mehanna, B.Sc. Pharm., M.Sc., Ph.D. School of Pharmacy Lebanese American University S Spring 2024-2025 At the conclusion of this chapter, You will be able to;  Define rheology and understand its application dur...

9/15/2024 Dosage Forms I M. Mehanna, B.Sc. Pharm., M.Sc., Ph.D. School of Pharmacy Lebanese American University S Spring 2024-2025 At the conclusion of this chapter, You will be able to;  Define rheology and understand its application during formulation and manufacturing  Explain Newton’s law of flow and its application  Contrast between the rheograms of Newtonian and non- Newtonian fluid and their flow features  Explain the concept of thixotropy and its application  Describe the mechanism of some traditional and modern viscometers 1  9/15/2024  Rheology: from the Greek word “rheo” means to flow and “logy’ means science = the science deals with the flow of liquids and the deformation of solids.  Viscosity: the resistance of liquid to flow  Areas of rheology application in pharmacy: a. Formulation and analysis of emulsions, pastes, suppositories, and tablet coating. b. Consistency and smoothness of medicinal and cosmetic creams, pasts and lotions. c. Involved in mixing and flow of materials, their packaging into containers and their removal prior to use as pouring from a bottle or extrusion from a tube. d. Rheological properties influence the selection of process equipment. 2  9/15/2024 Newtonian systems Newton’s law of flow Consider a block of liquid consisting of parallel plates of molecules. If the bottom layer is fixed and the top one is moved at a constant velocity, each layer will move by a velocity directly proportional to its distance from the stationary bottom layer.  The difference of velocity “dv” between two planes of liquid separated by a distance “dr” is rate of shearing, G, “dv/dr”.  The force per unit area “F’/A” required to induce flow is shear stress “F”.  Newton was the first to study the flow properties of liquid  The higher the viscosity of liquid “η”, the greater shearing stress required to produce a certain rate of shearing 3  9/15/2024 Shearing stress is directly proportion to rate of shear. F’/A = η dv/dr η = F/G η = F’ dr / A dv = dyne*cm / cm2.cm/sec = dyne. sec/cm2 (poise)  Poise is the shear force required to produce a velocity of 1cm/sec between two parallel planes of liquid each of 1 cm2 in area and separated by a distance 1cm. “centipoise”.  For Newtonian liquids, F versus G “flow curve= Rheogram” is straight line passing through the origin.  Fluidity is the reciprocal of viscosity. Φ = 1/η 4  9/15/2024 Rheogram  A graphical presentation of shear rate G and shear stress F  Known as consistency curve and flow curve  In Newtonian system, the slope is the fluidity. The greater slope of line, the greater is the fluidity and the lower is the viscosity. 5  9/15/2024 Non-Newtonian systems  Liquids doesn't follow Newton’s law of flow.  Three classes of non-newtonian liquids: a. Plastic b. Pseudoplastic c. dilatant 1. Plastic flow  Plastic flow curves don’t pass through the origin but intercept the shearing stress axis at a point “yield value”.  Materials exhibit plastic flow termed Bingham bodies in honor of the pioneer of modern rheology.  A Binghan body doesn’t begin to flow until a shearing stress corresponding to the yield value is exceeded.  The slope of rheogram is termed mobility “analogous to fluidity” and its reciprocal is plastic viscosity. 6  9/15/2024 2. Pseudoplastic flow  The viscosity of a pseudoplastic substance decreases with increasing the rate of shear (shear-thinning system).  The pseudoplastic flow exhibit by polymers in solution.  The rheogram started at the origin with no yield value.  The rheogram results from a shearing action on linear polymers. As the shearing stress is increased, normally disarranged molecules begin to put in order their long axes in the direction of flow.  This orientation reduces the internal resistance and allows a greater rate of shearing at each successive shearing stress.  Also, some solvent molecules may be released resulting in decreasing the viscosity. 7  9/15/2024  Plastic flow is associated with flocculated system. A yield value exists because of the contact between adjacent particles that should be break down before flow can occur.  A plastic system resembles a Newtonian system at a shear stresses ……………the yield value. 3. Dilatant flow  The viscosity of a dilatant substance increases with increasing the rate of shear (shear-thickening system).  The dilatant flow exhibit by heavy suspensions.  This type of flow is the inverse of that possessed by pseudoplastic systems.  Heavy suspensions have high concentration of small deflocculated particles.  At rest, particles are closely packed with minimal interparticle volume “voids” 8  9/15/2024  The amount of vehicle in the suspension is sufficient, however, to fill voids and permits particles to move relative to one another at low rates of shear.  As shear stress is increased, the bulk system expands “dilates”. The particles take an open form of packing, such arrangement leads to increase in interparticle void volume. The amount of vehicle becomes insufficient o fill the voids so the resistance to flow increases.  These liquids may damage the processing equipment. Thixotropy  Isothermal and slow recovery, on standing of a material, of a consistency lost through shearing (gel-sol-gel isothermal transformation).  In Newtonian systems, the curves are identical and superimposable.  In pseudoplastic systems, the down curve is displaced to the left of upcurve, showing that the material has a lower consistency at any one rate of shear on the downcurve than it had on the upcurve. 9  9/15/2024  The shear rate of a thixotropic material is increased in a constant manner and then decrease at the same rate back results is the so-called hysteresis loop.  The area of hysteresis loop used as a measure of thixotropic breakdown. 10  9/15/2024 Thixotropy in formulation Thixotropy is a desired property in liquid pharmaceutical systems that should have high consistency in the container and pour and spread easily. a. well-formulated Suspensions won’t settle readily in the container, will become fluid on shaking and will remain long enough for a dose be dispensed. Finally, it will retain consistency to maintain the particles in a suspension state. b. Emulsions, lotions, creams, ointment, and parenteral suspensions for IM depot. Determination of Rheological properties Choice of viscometer  Successful determination and evaluation of rheological properties of any system depend on choosing the correct instrumental method.  Single-point viscometers “viscometers operate at a single shear rate”, provide a single point on the rheogram, extrapolation of a line through this point to the origin will result in complete rheogram of…………..liquids 11  9/15/2024  Multipoint viscometers “viscometers operate at a variety of shear rates”, are able to produce a complete rheogram of………………...liquids.  For example, multipoint evolution of pseudoplastic material would allow assessment of viscosity of a suspending agent at rest “……..shear rate”, while being shake “………..shear rate”. Single point viscometer can’t describe this change. Viscometers I. Single-point viscometers: a. Capillary viscometer b. Falling-sphere viscometer II. Multipoint viscometers: a. Cup and bob viscometer b. Cone and plate viscometer 12  9/15/2024 Capillary viscometer  The viscosity of a Newtonian liquid can be determined by measuring the time required for a liquid to pass between two marks as it flows by gravity through a capillary tube as an Ostwald viscometer.  The time of flow of the tested liquid is compared with that of a liquid of known viscosity “usually water”.  The viscosity is determined by:  η1 / η2 = ρ1 t1 / ρ2 t2 Ostwald viscometer 13  9/15/2024 Cup-and-bob viscometer  The sample is sheared in the space between the outer wall of a bob and the inner wall of the cup.  The different instruments either based on whether the torque results from rotation of the bob or the cup: a. Couette-type of viscometer as MacMichael viscometer; the cup is rotating. The resultant torque is proportional to the sample viscosity. b. Searle-type of viscometer as Brookfield viscometer; the bob is rotating. The torque is measured by a sensor in the drive to the bob. Principle of cup-and-bob rotational viscometer 14  9/15/2024 Cone –and-plate viscometer  The sample is placed at the center of the plate, which is then raised into position under the cone. The cone is rotating and the sample is sheared in the narrow gap between the stationary plate and the rotating cone.  The rate of shear in revolution per min is increased and decrease by a dial and the torque (shearing stress) produced on the cone is read on the indicator scale.  A plot of shear rate “sec-1” versus shear stress ‘’dyne/cm2” 15  9/15/2024 Advantages over cup and bob viscometer: a. The rate of shear is constant through out the entire sample being sheared. b. Time saving in cleaning and filling c. Requires smaller sample volumes ”0.1-0.2 ml” while cup and bob requires 20-50 ml. d. Efficient in determining the area of hysteresis Thank You S 16