Physical Pharmacy Lecture, Module 1 PDF

MODULE 1 reading the meniscus weighing operations matching colors PHYSICAL PROPERTIES OF THE SUBSTANCE...

MODULE 1 reading the meniscus weighing operations matching colors PHYSICAL PROPERTIES OF THE SUBSTANCE making calculations A. Intensive 2. INDETERMINATE ERROR - Depends on the kind of matter present - Occur by accident or chance, and they vary from Eg: Temperature, Pressure, Density, Viscosity, Surface one measurement to the next. Tension, Specific Gravity Ex: B. Extensive natural fluctuations that occur in the - Depends on the quantity of matter in the system measurement Eg: Mass, length, volume CLASSIFICATION OF PHYSICAL PROPERTIES PRECISION VS ACCURACY 1. ADDITIVE PROPERTY Precision -depends on the sum of the individual properties - is the measurement of the agreement of data of the components present in a system Accuracy a. MOLECULAR WEIGHT -is the agreement between the data and the true Determine the molecular weight by adding the value atomic weights of the atoms in a chemical formula VARIABILITY MEASUREMENT FOR DISPERSION b. MOLAR VOLUME 1.Range - determined by adding atomic volumes 2.Mean Deviation 3. CONSTITUTIVE PROPERTY 3. Standard Deviation - depends on the type and arrangement 4.Variance a. Solubility 5. Absolute Error b. Optical Activity 6. Relative Error c. electromagnetic Properties Central Tendency: Mean, Median, Mode 4. COLLIGATIVE PROPERTY Arithmetic Mean (x-x)- is obtained by adding - depends on the number of components together the results of the various measurements A. Vapor Pressure Lowering components and dividing the total by the number N of the B. Boiling Point Elevation measurements. C. Freezing Point Depression MEDIAN D. Osmotic Pressure - Middle value of a range of values when they are BASIC PRINCIPLE ON MEASUREMENT arranged in rank order. (from lowest to highest) 3 Things Necessary to Describe an Object Example: 1.Numerical Value of the Property Median value of the list; 1 2 3 4 5 2. Dimensions of the Property MODE 3. Units which the Value is expressed -The value in the data set that occurs most often. FUNDAMENTAL DIMENSIONS/ MEASUREMENTS -Not commonly used in the pharmaceutical DIMENSION SYMBOLS Cgs unit Si Unit sciences. LENGHT L cm meter Example: 1 2 3 4 4 5 5 5 6 9 10 MASS M g kg MODULE 2: STATES OF MATTER TIME t sec sec A. FORCES OF ATTRACTION TEMPERATURE T K K 1. Intramolecular and Intermolecular attraction 2.van der Waals Forces ERRORS AND DESCRIBING VARIABILITY 3. Ion-dipole 4. Ion-induced dipole 1. DETERMINATE AND CONSTANT ERROR 5.Hydrogen bonding -Are those that although some can be avoided or B. STATES OF MATTER determined and corrected, they are present in 1.Gaseous State measurement and affect all observations of a 2. Liquid State series in the same way. 3.Solid State Ex: C. TRANSITION STATE errors in the calibration 1. Processes involved operations of the measuring instrument 2. Factors affecting phase transitions impurities in reagents and drugs 3. Phase Rule, Phase Diagrams and Eutectic biased personal errors Mixtures pouring and mixing GAVIETA, ZA| 2-D1 | P age  FUNDAMENTAL OF SUBATOMIC PARTICLES Electrostatic interaction of H with highly electronegative atoms (S,N,CL,F,O) PARTICLES SYMBOLS CHARGE MASS Intermolecular ELECTRON -e -1 0.0005486 - between molecules amu PROTON P+ 1 1.007276 Intramolecular amu - in the same molecules NEUTRON n° 0 1.008665 3.lon-Dipole amu - attractive force between an ionic compound and polar compound Example: NaCl and Water Explains solubility of The protons and neutrons are located in the ionic substances in water A+ nucleus. They are collectively called nucleons. 1. Ion-Induced dipole The electrons orbit around the nucleus they dictate the size of the atom and they are responsible for between an ionic compound and a non- polar the formation of bond. compound Induced by proximity of a charged ion to a non- Binding Forces Between Molecules/Compounds polar molecule Cohesive forces like/similar molecules Adhesive forces - unlike molecules This explains the solubility of iodine crystals in the presence of KI TYPES OF INTERMOLECULAR ATTRACTIVE STATES OF MATTER FORCES 1. Solid 1. van der Waal's Forces 2. Liquid a. Dipole-dipole (Keesom Forces) 3. Gas b. Dipole-Induced dipole (Debye Forces) 4. Plasma c. Induced Dipole-Induced Dipole (London 5. Boisen Condensates Dispersion) KINETIC MOLECULAR THEORY 2. Hydrogen Bonds 3. Ion-Dipole Explain the properties of the different states of 4. Ion-Induced dipole matter in terms of forces between the particles of van der Waal's Forces matter and the energy they possess. -forces of attraction that binds covalent molecules ASSUMPTIONS OF KINETIC MOLECULAR a. Dipole-dipole (Keesom Forces) - two polar THEORY molecules Matter is composed of very tiny particles. Example: H20, HCl, Alcohol, Acetone,Phenol 'The particles of matter are in constant motion. b. Dipole-Induced dipole (Debye Forces) The particles of matter do not lose energy in - attractive force between a polar and a non-polar collisions. molecule SOLID STATE Example: ethyl acetate, ether c. Induced dipole-induced dipole having a fixed shape and being nearly incompressible (London/Dispersion Forces) strong intermolecular forces. two non-polar molecules solids are characterized by shape, particle size induce polarity between non-polar and melting point; some solids are volatile enough Responsible for the liquefaction of gases to have a sublimation point. Example: carbon disulfide, CCl4, Hexane X-ray diffraction- is a method of crystal lattice 2. Hydrogen Bonds determination GAVIETA, ZA| 2-D2 | P age main types 1.Isotropic- exhibit similar properties in all 1. Crystalline directions. (amorphous and cubic crystals) 2. Amorphous 2. Anisotropic - showing different characteristics 3. Polymeric (electric conductance, refractive index, rate of Crystalline Solid solubility) in various directions along the crystal. The molecules or atoms are arranged in repetitious (Beeswax and paraffin - appears to be amorphous, three- dimensional lattice units infinitely throughout assume crystalline arrangement when heated and the crystal. then allow to cool slowly 7 COMMON LATTICE UNITS (UNIT CELL) Examples: Petrolatum - contains both crystalline Cubic-Sodium Chloride and amorphous Antibiotic (Novobiocin acid) - Tetragonal - Urea crystalline form/amorphous form Orthorhombie - Ritonavir Form II Polymeric Solid Rhombohedral - Iodine Polymers are large molecules formed by the Hexagonal- Iodoform covalent assembly of smaller molecules Monoclinie- Sucrose, Ritonavir Form I (monomers) into a chain or network of repeating Triclinie- Boric acid structural units. CRYSTALLINE MATERIALS A.Natural - rubber, polypeptides and cellulose Have definite melting points. B. Synthetic and Semisynthetic - plastics used in Found in pharmaceutics including homomeric packaging and devices (polyvinyl chloride, crystals and heteromeric crystals - solvates, salt polyethylene, and polystyrene) and those used in crystals and cocrystals. controlled release devices. Solvates - when a solvent is incorporated into the Uses lattice a.) Help stabilize the amorphous drug in the solid Salt Crystals - lattice accommodate other state and may a) help prevent crystallization upon molecules, such as acids and bases, to form salts. dissolution. b) The drug: polymer ratio is an important Cocrystals- A homogeneous, multicomponent consideration when making dispersion and can be phase of fixed stoichiometry where the chemical influenced by the polymer used. entities are held together in a crystal lattice by c.) Used as excipients in solid, semisolid, and intermolecular forces. liquid formulations. Amorphous Solid POLYMORPHISM Solid material is referred to as amorphous, Substance that exists in more than 1 crystalline when there is no long-range order over many form. molecular units to produce a lattice or crystalline structure. They have different melting points, x-ray These solids are referred to as glasses diffraction patterns and solubilities (nonequilibrium solid form) or possibly as TYPES OF POLYMORPHISM supercoiled liquids (a viscous equilibrium liquid Enantiotropic - when a change from one form) because of the random order of arrangement polymorphic form to another is reversible and the distortion of the shape under pressure. Amorphous Materials Do not possess a melting point but are defined Monotropic - when the transition takes place in by a glass transition (Tg) temperature, which is the temperature where amorphous material converts from a glass to supercooled liquid upon heating. EXAMPLE OF DRUGS IN DIFFERENT TYPES OF AMORPHOUS SOLID POLYMORPHIC FORMS GAVIETA, ZA| 2-D3 | P age Theobroma oil/ Cacao butter - use as a suppository resulting from evaporation of a liquid (or solid) base above a sample of the liquid (or solid) in a closed a. Unstable gamma form melt-18 container. B.Alpha form melt - 22 PHYSICAL PROPERTIES OF LIQUIDS C.Beta prime form melt -26° Does depend on the temperature. d.Stable beta form melt -34.5" Note: 33° is the lowest possible temperature to Vapor pressure and boiling point are inversely melt cacao and to prevent the crystal nuclei from related. destruction (35 "stable beta crystal destroy) As VP rises, BP falls. 2.Different polymorphs of drugs show different At room temperature, the VP of water is about solubilities 20 mm Hg a.SULFAMETER- form lI more active orally in human than form Ill which is more available in the Upon heating, VP increases market When the temperature reaches 100C (212 F), b. Polymorphs of chloramphenicol palmitate has a the VP of water is 760 mmHg or less, depending significant influence on the biologic activity c. on the elevation, and the water passes Cortisone acetate- 5 different forms and 4 are spontaneously into the vapor or gas phase. unstable in the presence of water due to caking, CRITICAL TEMPERATURE heating or grinding under water - the temperature above which a liquid above 3. Tamoxifen citrate - antiestrogenic and which a liquid can no longer exist. antineoplastic drug used to treat breast cancer and CRITICAL PRESSURE- the pressure required to post-menopausal symptoms liquify a gas at its critical temperature Form A - metastable polymorph (less organized) CLAUSIUS-CLAPEYRON’S EQUATIONS: Form B-stable held by hydrogen bonding Gives the relationship of vapor pressure and the ESTOGENS -essential hormone for the development absolute temperature of female sex characteristics. Based on studies the crystals (4) forms found contain solvent molecules and classified as solvates rather than polymorph. Solvates are sometimes called pseudo polymorphs. LIQUID STATE VAPOR PRESSURE OF LIQUID Denser than gases and possess less kinetic When the rate of condensation equals the rate energy than do gases. of vaporization at a definite temperature, the vapor becomes saturated and a dynamic equilibrium is Flows very readily, influenced by friction. established Can be frozen (solids) The pressure of the saturated vapor above the liquid is then known as the equilibrium vapor -Have boiling point (gases) pressure. Have vapor pressure and surface tension. The presence of a gas such as air above the A. BOILING POINT liquid would decrease the rate of evaporation, but it would not affect the equilibrium pressure of the - the temperature at which the vapor pressure of a vapor. liquid equals the atmospheric pressure. METHODS OF DETERMINING VAPOR HEAT OF VAPORIZATION PRESSURE - heat supplied at the boiling point to effect that 1. Manometer vaporization of the substance. 2. Isopiestic method - used for precise VAPOR PRESSURE determination of vapor pressure -The equilibrium pressure of a vapor above its 2. Thermoelectric method - measure change in liquid (or solid), that is, the pressure of the vapor potential as a solution as a solution of known vapor GAVIETA, ZA| 2-D4 | P age pressure and an unknown evaporate in a chamber LIQUEFACTION cannot occur if the temperature is maintained at constant humidity elevated sufficiently irrespective of the pressure SURFACE TENSION applied. Surface tension of a liquid is considered two IMPORANCE OF FORMULATION IN THE FORM OF dimensional AEROSOL Therefore, the dimensions of surface tension are ANTISEPTICS are sprayed into skin to cover force per unit length: generally, the units used are larger surface area and with a minimum discomfort dynes.cm" 1 to patients Generally, the surface tension of liquids LOCAL ANAESTHETICS are sprayed into area decreases with an increase in temperature. without causing discomfort to patients Measurement of surface tension: Capillary Method A means to introduce drugs into body cavities D. VISCOSITY and passages Reciprocal of fluidity Drugs with poor oral bioavailability Force of friction that tends to retard movement in FREEZING POINT- is the temperature at which there a fluid body is an equilibrium between the solid and the liquid Resistance of a liquid to flow phases TYPES OF VISCOSITY HEAT OF FUSION - takes place when freezing takes 1.ABSOLUTE & DYNAMIC VISCOSITY - measurement place with the evolution of heat in order to melt the of the fluid's internal resistance to flow (expressed substance, heat must be supplied. as poise or Pa.s) VAPOR PRESSURE OF LIQUID 2. RELATIVE VISCOSITY- viscosity in relation to a GASEOUS STATE standard Higher kinetic energy that produces rapid motion, 3.KINEMATIC VISCOSITY - absolute are held together by weak intermolecular forces. viscosity/dynamic viscosity divided by the density No regular shape of the liquid at a specific temperature (Stokes or Capable of filling all available space Centistokes Compressible MEASUREMENT OF VISCOSITY Many gasses are invisible 1.CAPILLARY VISCOMETER - the viscosity of a A gas is consisting of infinitely small independent Newtonian liquid can be determined by measuring particles, moving at random in space and the time required for the liquid to pass between two experiencing perfectly elastic collisions (ideal gas) marks as it flows by gravity through a vertical tube LAW GOVERNING GASES (Ostwald Viscometer) nid2t2 = n2dit1 BOYLE’S LAW- relationship of pressure and 2.CUP AND BOB VISCOMETER- the sample is volume at constant temperature. sheared in the space between the outer wall of a P1V1= P2V2 bob and the inner wall of a cup into which the bob CHARLE’S LAW - relationship of volume and fits absolute temperature at constant pressure 3. FALLING SPHERE (HOEPLLER BALL FALLING) - a VT2=V2T, glass or steel ball rolls down at almost vertical AMONTON’S OR GAY LUSSAC’S LAW-relationship glass tube containing the test liquid at a known of pressure and absolute temperature at constant constant temperature. The rate at which a ball of a volume particular density and diameter fall is an inverse PTa=P2T1 function of the viscosity of the sample. COMBINED GAS LAW: P,V,T.=PeV2T, 4. CONE PLATE VISCOMETER (FERRANTI SHIRLEY) - AVOGRADO’S LAW - the volume occupied by a the sample is placed at the center of the plate gas is directly proportional to the number of moles which is then raised into a position under the at STP, at STP the volume occupied by 1 mole of cone. any gas is equal to 22.4L. 5. BROOKFIELD DALTON’S LAW OF PARTIAL PRESSURE "is the 6. SAYBOLT pressure a gas would exert if it alone occupied the 7.CLINDER METGOD (co-axial) whole volume of the mixture.” LIQUEFACTION OF GASES IDEAL GAS LAW - Achieved by lowering the temperature (gas PV=nRT molecules loss some of its kinetic energy) and where: increasing the pressure (molecules come nearer P - pressure together and are brought within the sphere of V-volume n-number of moles intermolecular attraction). GAVIETA, ZA| 2-D5 | P age R-universal gas constant are also use to enhance physical stability of T- temperature emulsion In order for a gas to be ideal, its behavior must TYPES OF LIQUID CRYSTALS follow the Kinetic- Molecular Theory whereas 1.Simetic (soap or grease-like) the Non-Ideal Gases will deviate from this theory 2. Nematic (thread-like) due to real world conditions. 3. Cholesteric State STANDARD TEMPERATURE AND PRESSURE SUBSTANCE THAT FORM MESOPHASE Standard temperature: 0°C =273.15 K 1. Rigid Standard pressure 1 atmosphere = 760 mmlg = 2. Organic 101.3 kPa 3. Possess strong dipoles and easily polarizable Standard volume of 1 mole of an ideal gas at STP: 4. Elongated and rectilinear in shape 22.4 liters MESOPHASE RESULT FROM: Avogadro's number 6.00 x 10²³ Heating solids (thermotropic liquid crystals) DESCRIBED THE BEHAVIOR OF REAL GASES Action of certain solvents on solids Real Gases: (lyotropic liquid crystals) Not composed of infinitely small particles Particles are non-elastic SUPERCRITICAL FLUID STATE They attract to a certain extent Supercritical Fluid State Van der Waaal’s Equation ⁃ Have properties intermediate between those of liquids and gases -Can permeate solid substances (gas property) - Have high density regulated by pressure (liquid property) THE PLASMA STATE - Plasma are a lot like gasses, but the atoms are different because they are made up of free IMPORTANCE OF SUPERCRITICAL FLUID electrons and ions of the element Plasma is an ionized gas STATE BOSE CONDENSATES Supercritical fluids are finding increasing - a state of matter that occurs at extremely low application in the pharmaceutical industry for the temperature, near absolute zero. These solution of difficult processing problems temperatures are too low to occur anywhere on Supercritical fluids exhibit a pressure- tunable earth except in laboratory experiments. dissolving power, they possess a liquid like density Liquid Crystalline State (MESOPHASE) and thus a high solvent strength. > a state of matter intermediate between liquid and Ideally suited for developing processes for solid extracting, purifying, and recrystallizing fine chemicals and pharmaceuticals and producing new PROPERTIES OF SIGNIFICANCE OF LIQUID PHASE CHANGES CRYSTALS Matter undergoes phase changes or phase 1.Molecules are mobile (property of a liquid) transitions from one state of matter to another: 2. Birefringence - the light passing through them is Typically"occur when the temperature or pressure divided into two components with different of a system is altered. refractive indices (property of a solid) When temperature or pressure increases, 3.Show consistent color changes and therefore molecules interact more with each other used to detect areas of elevated temperature When pressure increases or temperature under the skin that may be due to disease process decreases, it's easier for atoms and molecules to 4. They have structures believed to be similar to settle into a more rigid structure. -When pressure is those in cell membranes released, it's easier for particles to move away 5. Nematic liquid crystals are sensitive to electrie from each other. fields (used as sensors) 6. Smectic mesophase has application in the solubilization of water-insoluble materials. 'They GAVIETA, ZA| 2-D6 | P age  PHASE RULE Law relating variables of a system in IDEAL GAS LAW thermodynamic equilibrium deduced by the American physicist J. Willard Gibbs in his papers on thermodynamics. Systems in thermodynamic equilibrium are generally considered to be isolated from their environment in some kind of closed container but many geological systems can be considered to obey the phase rule. SAMPLE PROBLEM THE VARIABLES ARE Determine the volume of occupied by 2.34 grams The number of phases P (solid, liquid, and gas of carbon dioxide gas at STP. not necessarily of a single chemical component) Solution: The number of chemical components C (pure 1) Rearrange PV = nRT to this: compounds or elements) V=nRT/P The number of degrees of freedom F of intensive n= gx m.W variables (temperature, pressure, and percentage 2) Substitute: composition V=[(2.34g/44.0 gmol/1) (0.08206 L atm mol K -1) The phase rule states that F= C-P + 2. (273.0 1.00 atm V=1.19 L PHASE RULE A 12.0"g sample of gas occupies 19.2 L at STP. Thus, for a one-component system with one What is the molecular weight of this gas? phase, the number of degrees of freedom is two, Use PV= nRT: and any temperature and pressure, within limits, (1.00 atm) (19.2 L) = (n) (o.08206) (273 K) can be attained. n= 0.8570518 mol With one component and two phases-liquid and 2) Determine the molecular weight: vapor, for example- only one degree of freedom.12.0 g / 0.8570518mol = 14.0 g/mol exists, and there is one pressure for each temperature. For one component and three phases (e.g., ice floating in water with water vapor above it, in a closed container), there is no degree of freedom, and temperature and pressure are both fixed at what is called the triple point SAMPLE PROBLEM 1. Determine the degrees of freedom of a system containing either ice, water or water vapor Solution: F=C-P+2 F=1-1+2=2(bivariant) 2. Calculate the degrees of freedom for a system containing water in equilibrium with its vapor Solution: F=C-P+2 F=1-2+2= 1 (univariant) PHASE DIAGRAM PHASE DIAGRAM Graph showing the limiting conditions for solid, liquid, and gaseous phases of a single substance or of a mixture of substances while undergoing changes in pressure and temperature or in some other combination of variables, such as solubility and temperature. GAVIETA, ZA| 2-D7 | P age