Pharmaceutical compounding I Colloidal and Surface-Chemical Aspects of Dosage Forms Dr. rer. nat. Rebaz H. Ali
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1 University of Sulaimani School of Pharmacy Dept. of Pharmaceutics Pharmaceutical Compounding Pharmaceutical compounding I Colloidal and Surface-Chemical Aspects of Dosage Forms Dr. rer. nat. Rebaz H. Ali
2 Outlines Rheology Introduction Mechanical properties of solids Flow of liquids Newtonian liquids Non-Newtonian liquids Colloidal dispersions 2/13/2017 Pharmaceutical Compounding 2
3 Introduction Rheology is the branch of physics that deals with deformation and flow of matter. Deformation describes the change of matter in terms of shape or volume, or both. Increasing interest in rheological methods in the medical and biological sciences: A. A change of the rheological behavior of certain body fluids such as mucus, saliva, blood, or synovial fluid. B. In pharmaceutics more viscous materials require larger amounts of energy during mixing. The viscosity might be reduced by the application of heat, which could reduce the mixing time and improve product homogeneity. C. Patient compliance. Application of stiff creams Flow through a hypodermic needle, Pouring from bottle 2/13/2017 Pharmaceutical Compounding 3
4 Introduction Rheology systems and stresses: Solids: have a constant volume and permanent shape, and are capable of supporting loads. Liquids have constant volumes at constant temperature, variable shape, and support no loads. Gases have neither constant volume nor permanent shape. Stress and Strain Deformation is the result of a force acting on or within a body, its extent depends on the magnitude of force per unit area (F/A), i.e., the stress (Pa, Nm -2 ). As a consequence of the stress applied, the body will change its shape, and as a result, there will be a change in length of the body, i.e., strain. 2/13/2017 Pharmaceutical Compounding 4
5 Outlines Rheology Introduction Mechanical properties of solids Flow of liquids Newtonian liquids Non-Newtonian liquids Colloidal dispersions 2/13/2017 Pharmaceutical Compounding 5
6 Percent élongation Mechanical properties of solids Elastic solids are deform under stress, but once the stress is removed, they regain their original shape, and the strain returns to zero. Point Y is the yield point or elastic limit, and the corresponding stress is the yield stress. If the stretching process of polyethylene or steel is stopped before point Y, they will snap back to their original length. Beyond Y, the solids undergo permanent deformation R Breaking point from which they do not recover upon the removal of stress, this called plasticity. P G Yield point S Stress, dyne/cm 2 2/13/2017 Pharmaceutical Compounding 6
7 Mechanical properties of solids cont. Steel has a high modulus (young s modulus E; it s a characteristic property of solids, representing their stiffness or hardness). E = stress = F/A strain l The horizontal portion YAH, the material is ductile; it flows under practically constant stress like a viscous liquid. If the stress is released at A, the sample retracts along AC. The nonrecoverable deformation OC is called permanent set. R is the elongation at the break, and the stress corresponding to B is the ultimate strength or tensile strength. B 2/13/2017 Pharmaceutical Compounding 7
8 Mechanical properties of solids cont The area OLYAHBRCO under the stress-strain curve is the energy or work required to break or rupture the material. It measures the material s toughness. Glass is hard and brittle. Steel is tough. Plastics are medium-hard or soft. B 2/13/2017 Pharmaceutical Compounding 8
9 Outlines Rheology Introduction Mechanical properties of solids Flow of liquids Newtonian liquids Non-Newtonian liquids Colloidal dispersions 2/13/2017 Pharmaceutical Compounding 9
10 Flow of liquids Liquids do not retain their shape; the smallest stresses, if applied for long enough time, produce infinite deformation. If water and castor oil are poured from bottles, water flows a thousand times faster, i.e., its rate of shear is a thousand times greater. H γ = V H = cm sec.cm = sec When liquid flows through a cylindrical tube of small diameter the velocity is zero at the wall of the tube, and maximum in the center. 2/13/2017 Pharmaceutical Compounding 10
11 Flow of liquids cont. Vasodilator drugs like nitroglycerin increase the radius of blood vessels by relaxing the vascular smooth muscles. The viscosity of a fluid may be described simply as its resistance to flow or movement. Thus water, which is easier to stir than syrup, is said to have the lower viscosity. Viscosity η is defined as the ratio of shear stress τ to rate of shear γ. η = τ γ = F/A = dyne/cm2 1/sec 1/sec = Pa.s 2/13/2017 Pharmaceutical Compounding 11
12 Outlines Rheology Introduction Mechanical properties of solids Flow of liquids Newtonian liquids Non-Newtonian liquids Colloidal dispersions 2/13/2017 Pharmaceutical Compounding 12
13 Newtonian liquid The viscosity of simple liquids (i.e., pure liquids consisting of small molecules and solutions where solute and solvent are small molecules) depends only on composition, temperature, and pressure. It increases moderately with increasing pressure and markedly with decreasing temperature. For solutions of solid solutes, the viscosity usually increases with concentration. When the viscosity is independent of the shear stress or the rate of shear, the liquid called Newtonian liquid. 2/13/2017 Pharmaceutical Compounding 13
14 Newtonian liquid Plots of shear stress (on the y axis) as a function of the rate of shear (on the x axis) are referred to as flow curves or rheograms. A has a higher viscosity than B because α > β The slope, f, is known as fluidity and is the reciprocal of viscosity, η: B Shear rate, S -1 A Rheograms or flow curves of two Newtonian liquids. Shear stress, N/m 2 2/13/2017 Pharmaceutical Compounding 14
15 Outlines Rheology Introduction Mechanical properties of solids Flow of liquids Newtonian liquids Non-Newtonian liquids Colloidal dispersions 2/13/2017 Pharmaceutical Compounding 15
16 Non-Newtonian liquid A. Plasticity: the flocculated particles in concentrated suspensions do not flow at low shear stresses (exhibiting reversible deformation like elastic solids) but flow like liquids above their yield value (i.e., yield stress) This termed plastics or Bingham bodies. The more flocculated the suspension, the higher will be the yield value 2/13/2017 Pharmaceutical Compounding 16
17 Non-Newtonian liquid cont. B. Shear-thinning Fluids. Many colloidal systems, especially polymer solutions and flocculated solid/liquid dispersions, become more fluid the faster they are stirred. Shear-thinning behavior is often referred to as pseudoplasticity. Shear-thinning behavior is an example of non-newtonian flow because the viscosity, at constant temperature and composition, decreases with increasing shear. Examples are solutions of polymers, such as MC or NaCMC and gums such as tragacanth or acacia. 2/13/2017 Pharmaceutical Compounding 17
18 Non-Newtonian liquid cont. The macromolecules tend to assume roughly spherical shapes, which surrounded by a sheath of water of hydration. The viscosity of the solution is reduced in these ways: The polymer chain become elongated and thus offer less resistance to flow. The amount of water trapped inside the coils decreases. Brownian motion will lead to a rebuilding of the inner structure in many cases 2/13/2017 Pharmaceutical Compounding 18
19 Non-Newtonian liquid cont. C. Dilatancy or shear-thickening is an increase in viscosity with increasing shear. It is shown by concentrated (> 50%) deflocculated dispersions as the amount of liquid present is not much larger than that needed to fill the voids between the particles As shear stress is increased the particles are rearranged which leads to a significant increase in interparticle void volume. The amount of vehicle remains constant, accordingly, resistance to flow increases because particles are no longer completely wetted, or lubricated, by the vehicle. Example is suspensions of starch in water. 2/13/2017 Pharmaceutical Compounding 19
20 Non-Newtonian liquid cont. Thixotropy is the gradual decrease in viscosity with increased shear followed by a gradual recovery of the original structure. Their apparent viscosity depends on temperature, composition, shear stress, and the previous shear history and time under shear. It usually related to shear thinning materials. For shear thickening samples, called negative thixotropy. 2/13/2017 Pharmaceutical Compounding 20
21 Thank you for your attention! 2/13/2017 Pharmaceutical Compounding 21
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