Physical Pharmacy Lecture PURIFICATION AND CLARIFICATION Purification removes impurities in the initial products and by-products Impurities

s adulterants, foreign materials General Standard test Official monograph USP, NF compedium II. Specific Test for Impurities No single test is valid for the purity of active ingredient Ex. Biological method - test use to determine the amount of active ingredient Test use to determine impurities present in in biological product Different processes involve in Purification 1. Separation of Gases from gases a. Condensation b. Adsorption by solid c. Absorption by solid 2. Separation of Gas from Liquid a. Evaporation dec. solubility of gas from liquid b. Aeration done by bubbling in solution gas through liquid that is to trap the gaseous impurities in the bubbles and are removed c. Adsorption gaseous impurities are removed on the surface upon the interaction of the gas adsorbent 3. Separation of liquid from liquid a. Conversion to a gaseous phase i. Sublimation ii. Evaporation iii. Distillation b. Conversion to solid state i. Decantation ii. Filtration iii. Evaporation c. Conversion by chemical reaction d. Conversion to an immiscible liquid phase 4. Separation of a liquid and a solid a. Decantaion d. siphoning b. Filtration e. centrifugation c. Colation process done by pouring the mixture upon a cloth and porous substance which will permit the fluid to pass through but will retain the solid 5. Separation of solids a. Convert one phase to vapor phase i. sublimation ii. pseudo sublimation carried out by heating the impure solid substance until it liquefies but it must be below boiling point, blast of air is blown across the surface of melted solid carrying the vapor into condensation chamber , vapor will solidify and the non-volatile impurities being removed b. Convert to liquid phase i. Washing - Use solvent to remove impurities ii. Extraction process removing soluble components from a crude drug by extraction with a solvent 1. Percolation 2. distillation Clarification special type of purification that is the removal of finely divided particles which are suspended from a liquid preparation. I.

Processes of clarification 1. Facilitation of setting decrease the viscosity of the liquid so that the particle will either rise or fall 2. Precipitation formation of solid particles in a previously clear solution by physical or chemical process Different process of precipitation 1.Precipitation by heating 2.Precipitation by cooling 3.Crystallization 4.Granulation when the precipitate are rapidly formed (bigger ppt) Different types of precipitate 1.Crystalline precipitate 2.Amorphous precipitate 3.Light precipitate 4.Heavy precipitate STATES OF MATTER I. GASEOUS STATE gaseous molecules travel in random paths and collide not only with one another but also with the walls of the container in which they are confined hence they exert Pressure ( Force per 3 3 unit area) expressed in dyne/cm or torr or mmHg, has a volume expressed in Liters, cc or ft and a temperature expressed in absolute or Kelvin scale ( 0C = 273.15K) Gas Law A. Ideal gas law 1.Boyles law If the temperature remains constant, the volume of a given mass of gas varies inversely with pressure

Example: 100ml of gas are enclosed in a cylinder under a pressure of 760 torr. What will be the volume of the same gas at a pressure of 1520 torr?

2.Charles and Gay-Lussacs law If the pressure does not change, the volume of a given mass of gas is directly proportional to the absolute temperature

Example: The air in the tank has a pressure of 640mmHg at 23C, when placed under the sun, the temperature rose to 48C. What was the pressure in the tank?

Combination of these laws = Equation

Example 3 The gas temperature was 27C, pressure of 700nnHg and the volume of the gas is 80,000 ft . What was the gas volume at high altitude where the temp was -3C and the pressure is 400mmHg?

3.Ideal Gas Law combination of the laws, aka Henrys law

PV=nRT
R = gas constant = 0.08206Latm/Kmol or 8.314J/Kmol or 1.987 cal/Kmol
***volume of the gas at a standard T ( 273.15K) and Pressure( 1atm or 760mmHg) is equal to 22.14L (by experimentation) n = no of moles

Example What is the volume of 2 moles of an ideal gas at 25C at 760mmHg?

**Approximate MW of gas can be determined using ideal gas law wherein the no. of moles is equal to , where g = no of grams of gas and MW is the molecular weight

MW

Example If 0.30 of an unknown alcohol in the vapor state occupies 200ml at a pressure of 1 atm and a temp of 100C, what is the MW of the unknown alcohol?

B. Kinetic Theory of Gases - theory developed to explain the behavior of gases and to lend additional support to the validity of the gas laws 1.Gases are composed of particles called atoms or molecules, the total volume of which is so small as to be
negligible in relation to the volume of the space in which the molecules are confined. This condition is approximated in actual gases only at low pressures and high temperatures, in which case the molecules of the gas are far apart. 2.Particles of the gas do not attract one another, but instead move with complete independence; again, this statement applies only at low pressures 3.The particles exhibit continuous random motion owing to their kinetic energy. The average kinetic energy, E, is directly proportional to the absolute temperature of the gas, or E = (3/2)RT. 4.The molecules exhibit perfect elasticity; that is, there is no net loss of speed or transfer of energy after they collide with one another and with the molecules in the walls of the confining vessel, which latter effect accounts for the gas pressure. Although the net velocity does not change on collision, the speed and energy of the individual molecules may differ widely at any instant. More simply stated, the net velocity can be an average velocity of many molecules; thus, a distribution of individual molecular velocities can be present in the system.

C. Van der Waals Equation for Real gas

The fundamental kinetic equation is found to compare with the ideal gas equation because the kinetic theory is based on the assumptions of the ideal state. However, real gases are not composed of infinitely small and perfectly elastic non attracting spheres. Instead, they are composed of molecules of a finite volume that tend to attract one another. These factors affect the volume and pressure terms in the ideal equation so that certain refinements must be incorporated if equation (2-5) is to provide results that check with experiment. A number of such expressions have been suggested, the van der Waals equation being the best known of these. For 1 mole of gas, the van der Waals equation is written as

For the more general case of n moles of gas in a container of volume V, equation becomes

The term a/V2 accounts for the internal pressure per mole resulting from the intermolecular forces of attraction between the molecules; b accounts for the incompressibility of the molecules, that is, the excluded volume, which is about four times the molecular volume.

The Van Der Waals Constants for some Gases Gas a (liter2 atm/mole2) b (liter/mole) H2 0.244 0.0266 O2 1.360 0.0318 CH4 2.253 0.0428 H 2O 5.464 0.0305 Cl2 6.493 0.0562 CHCl3 15.17 0.1022
Example: A 0.193-mole sample of ether was confined in a 7.35-liter vessel at 295 K. Calculate the pressure produced using (a) the ideal gas equation and (b) the van der Waals equation. The van der Waals a value for ether is 17.38 liter2 atm/mole2; the b value is 0.1344 liter/mole

II.

LIQUID STATE Liquifaction of gases - When a gas is cooled, it loses some of its kinetic energy in the form of heat, and the

velocity of the molecules decreases. If pressure is applied to the gas, the molecules are brought within the sphere of the van der Waals interaction forces and pass into the liquid state. Because of these forces, liquids are considerably denser than gases and occupy a definite volume. The transitions from a gas to a liquid and from a liquid to a solid depend not only on the temperature but also on the pressure to which the substance is subjected. critical temperature - The temperature, above which a liquid can no longer exist . The critical temperature of water is 374C, or 647 K whereas the corresponding values for helium are 5.2 K. This serves as a rough measure of the attractive forces between molecules .

critical pressure - The pressure required to liquefy a gas at its critical temperature, which is also the highest vapor pressure that the liquid can have. The further a gas is cooled below its critical temperature, the less pressure is required to liquefy it. Waters critical pressure is 218 atm, and helium is 2.26 atm

Colligative Properties of Liquid -depend only on the concentration of the solute, not on the identity of the solute molecules. 1. Vapor pressure - The equilibrium pressure of the saturated vapor above the liquid, that is the vapor resulting from the evaporation of a liquid above a sample of a liquid in a close container. As the

2.

temperature of the liquid is elevated, more molecules approach the velocity necessary for escape and pass into the gaseous state. As a result, the vapor pressure increases with rising temperature. Boiling Point - The temperature at which the vapor pressure of the liquid equals the external or atmospheric
pressure surrounding the liquid. The atmospheric pressure at sea level is approximately 760 mm Hg; at higher elevations, the atmospheric pressure decreases and the boiling point is lowered. At a pressure of 700 mm Hg, water boils at 97.7C; at 17.5 mm Hg, it boils at 20C. In a dilute solution of a nonvolatile solute, the rise in boiling point is proportional to the number of solute molecules, regardless of their size and mass. Surface Tension force or unit area required to extend a surface - Force which resist expansion to a certain area * types of attractive forces a. Cohesive force exists between like molecules b. Adhesive force exist between unlike molecules - Suface tension of liquid refers to the amount of energy that is required to expand the surface per unit area * Methods of determining surface tension a. Capillary method the capillary tube of a radius r is dip into a liquid, the liquid is observed to rise to a height in the tube. - there are two force that exist that must be balanced 1. Force acting downward = a gravitational pull of liquid given by the form

3.

2.

Force acting upward = act along periphery capillary tube

of cylindrical bore( bet. Liquid and

Example: 3 An acetone with a surface tension of 23.7 dynes/cm at 20C and a density of 0.792gm/cm rises at a certain capillary tube at 1.5cm. Determine the radius of the capillary tube.

b. c. 4. 5.

Stalagmometer The principle is to measure the weight of the drops of the fluid falling from the capillary glass tube whose middle section is widened Tensiometer instrument for measuring surface tension of liquid

Decrease in freezing point - Another colligative property of solutions is the decrease in the freezing temperature of a solvent that is observed when a small amount of solute is dissolved in that solvent. Osmotic Pressure - helped to establish the fundamentals of modern physical chemistry and played a particularly important role in the early days of solution theory. Osmosis occurs whenever a liquid solution is in contact with asemipermeable membranei.e., a thin, porous wall whose porosity is such that some, but not all, of the components in the liquid mixture can pass through the wall. Osmotic pressure is the pressure which needs to be applied to a solution to prevent the inward flow of water across a semipermeable membrane. Osmotic pressure for a dilute solution is proportional to the number of solute molecules, it is a colligative property, and, as a result, osmotic-pressure measurements are often used to determine molecular weights, especially for large molecules such as polymers.

III.

SOLID STATE Characterized to have a definite volume, shape and mass Molecules are highly arranged in the structure Bonds are stable and strong

2 Types of Solid state A. Amorphous characterized to have indefinite arrangementswhich makes them shapeless and without definite order - Melting points varies over a range or temperature interval B. Crystalline - they have definite arrangement /configuration and they are characterized as species composed of structural unit with a a specific geometric pattern - crystals substance in which the atom or molecules are packed closely together in such a way that these atom/ molecules make up a highly ordered structure which is called the crystal lattice - crystal lattice refers to the arrangement order/ packaging of solid particles of crystals in a regular array. -different crystal lattice based on their dimensions a. one dimensional lattice the only geometric parameter is the repeating distance between the atoms or point ( one unit cell) b. two dimensional lattice a planar system, it has a 5 different arrangement /unit cells that can be constructed from the lattice point c. three dimensional lattice the unit cell is characterized by length a,b and c and the angles - Different Types of Crystals a. Ionic Crystal b. Metallic crystal c. Covalent crystal d. Molecular crystal - Different properties of crystal a. Isotropic b. Anisotropic c. Directional property d. Plane axes of symmetry e. Axes of symmetry f. Center of symmetry g. Polymorphism/ allotropism - Shapes of crystal a. Cubic b. Tetragonal c. Hexagonal d. Rhombohedral e. Orthorhombic f. Monoclinic g. Triclinic -dgmp