Physical Pharmacy Notes

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Physical Pharmacy •

application of physical chemistry in pharmacy

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study of physiochemical properties of substances used in drug formulation

FORCES OF ATTRACTION Intramolecular Forces •

forces of attraction within the molecule

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Types – Ionic & Covalent Bonds o Ionic Bond § Transfer of electrons between a non metal & a metal § observed in formation of salts o Covalent Bond § sharing of electrons between two non metals § observed in organic compounds

Intramolecular Forces •

forces of attraction between molecules

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Types – Binding & Attractive Forces o Binding Forces § Cohesion – similar molecules § Adhesion – different molecules § Repulsive – prevent molecules from annihilating each other o Attractive Forces § Van der Waals § Hydrogen Bond § Ion-Dipole § Ion-induced Dipole

Van der Waals Forces •

weak forces that involve the dispersion of charge across a molecule called a dipole o Keesom Forces (orientation effect) § Dipole-dipole § molecules are polar with permanent polar dipoles § Ex. water, HCl, ethanol, acetone, phenol o Debye Forces (induction effect) § Dipole-induced dipole § transient dipole induced by a permanent dipole § polar molecules produces temporary electric dipole in nonpolar molecules § Ex. Ethyl acetate, methylene chloride, ether o London Forces (dispersion effect) § Induced dipole- induced dipole § induce polarity between non polar molecules

responsible for liquefaction of gases Ex. Carbon disulfide, CCl2, hexane

Hydrogen Bond •

electrostatic interaction of H with highly electronegative atoms (S,N,Cl,F,O)

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accounts for unusual properties of water

Ion-Dipole Interaction •

polar molecules are attracted to either positive or negative charges

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occurs when salt is dissolved in a polar solvent

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solubility if crystalline substances in H2O

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quaternary ammonium + tertiary amine

Ion-Induced Dipole •

induced by close proximity of a charged ion to a non polar molecule

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responsible for the solubility of non polar molecules

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Ex. Iodine complex with salts

PHYSICAL PROPERTIES OF MATTER Additive •

depends on the total contribution of the atoms in the molecules

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Ex. MW, Mass

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↑ atoms = ↑MW = ↑Mass

Constitutive •

depends on the arrangement of the number & kind of atoms within a molecule

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Ex. Refactive Index, Optical Rotation

Colligative •

function of the number of species or particles present in a given solution

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Ex. Osmotic pressure elevation, Vapor Pressure lowering, Freezing Point Depression, Boiling Point Elevation

TYPES OF PROPERTIES Intensive •

independent of the amount of the substance in the system

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Ex. Temperature, Pressure, Density, Viscosity, Surface tension, Specific Gravity

Extensive •

depends on the quantity of substance in the system

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Ex. Mass, Length, Volume

Lorenzo Dominick Cid 2015

P1 & P2 = vapor pressures at T1 & T2 ∆Hv = molar heat of vaporization R = 1.987 cal/mole deg

STATES OF MATTER The Gaseous State Gas Laws •

refers to an ideal situation where no intermolecular interactions exist and collisions are perfectly elastic

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there is no energy exchanged upon collision

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Boyle’s Law o relates volume and pressure o constant temperature o PV = k

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Gay-Lussac and Charles’ Law o states that the volume and absolute temperature of a gas at constant pressure are directly proportional o V = kT Ideal Gas Law o PV = nRT o R = 0.08205 liter.atm/mole.K or 8.314 joules/mole.K or 1.987 cal/mole deg o n = number of moles

The Solid State •

have fixed shapes

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nearly incompressible

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have strong intermolecular forces

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very little kinetic energy

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atoms vibrate fixed positions about an equilibrium position, & so there is very little transitional motion

Crystalline Solids •

Solids whose structural units are arranged in a fixed geometric pattern or lattices

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definite shape

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orderly arrangement of units

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definite and sharp melting points

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6 Distinct Critical Systems Based on Symmetry o Cubic – Sodium Chloride o Tetragonal – Urea o Hexagonal – Iodoform o Monoclinic – Sucrose o Rhombic – I2 o Triclinic – Boric Acid

Kinetic Molecular Theory •

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

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The particles of the gas do not attract one another, but instead move with complete independence

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The particles exhibit continuous random motion owing to their kinetic energy

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glasses or supercooled liquids

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molecules are arranged in a random manner

The molecules exhibit perfect elasticity

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no definite melting points

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faster dissolution rate

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The Liquid State • •

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Critical temperature – temperature above which a liquid can no longer exist Critical Pressure o pressure required to liquefy a gas a critical temperature o highest vapor pressure of a liquid

Polymorphism •

condition where substances can exist in more than 1 crystalline form

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polymorphs have different melting points, x-ray crystals and diffraction patterns and solubility

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Theobroma Oil Polymorphs (Melting Points)

Boiling Point – the temp at which the vapor pressure of the liquid equals the external and atmospheric pressure

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Unstable γ form à 18°C

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α form à 22°C

Latent Heat of Vaporization o the quantity of heat taken up when a liquid vaporizes o it is liberated when a vapor condenses with a liquid

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β prime form à 28°C

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Stable β form à 34°C

Clausius-Clapeyron Equation •

Amorphous Solids

relationship of vapor pressure and absolute temperature of a liquid

log

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Types of Polymorphism o Enantiotropic – reversible o Monotropic – unidirectional transition

Freezing Point •

temperature at which liquid à solid

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melting point of a pure crystalline compound

P1 ∆Hv (T2 -T1 ) = P2 2.303 RT1 T2

Lorenzo Dominick Cid 2015

Latent Heat of Fusion •

Energy absorbed when 1g of a solid melts

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Heat liberated when it freezes

Liquid Crystalline State •

liquid crystals à intermediate between liquid and solid states

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may result from the heating of solids (thermotropic) or from the action of certain solvents on solids (lyotropic liquid crystals)

Two Main Types of Liquid Crystals •

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Smectic o Soaplike or greaselike o molecules are mobile in 2 directions o rotates in 1 axis Nematic o o o o

threadlike molecules are mobile in 3 directions rotates in 1 axis Cholesteric – special type of nematic

Supercritical Fluids

THERMODYNAMICS •

deals with the quantitative relationships of interconversion of the various forms of energy

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System – a well defined part of the universe under study

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Surroundings – the rest of the universe from which the observations are made

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Boundaries – physical or virtual barriers that separate a system from the surroundings

Types of Systems •

Open – energy and matter can be exchanged with the surroundings

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Closed – energy can be exchange with the surroundings but not matter

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Isolated – neither matter not energy can be exchanged with the surroundings

First Law of Thermodynamics •

Energy cannot be created nor destroyed, it can only be transformed into a different form

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Adiabatic – constant heat

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Isothermic – constant temperature Isochoric – constant volume Isobaric – constant pressure

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properties intermediate between those of liquids and gases

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formed from the gaseous state where the gas is held under a combination of temperatures and pressures that exceed the critical point of a substance

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Second Law of Thermodynamics •

Refers to the probability of the occurrence of a process based on the tendency of a system to approach a state of energy equilibrium

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Entropy

THE PHASE RULE (GIBB’S PHASE RULE) •

relates the effect of the least number of independent variables (T, P & C) among the various phases (S,L & G) that can exist in an equilibrium system containing a given number of components

Third Law of Thermodynamics •

𝐹 =𝐶−𝑃+𝑋 F = no. of degrees of freedom C = no. chemical components P = no. of phases X = variable dependent upod considerations of the phase diagram •

F – least number of intensive/independent variables that must be fixed to describe the system completely

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C – smallest number of constituents by which the composition of each pase in the system at equilibrium can be expressed in the form of a chemical formula or equation

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P – number of homogenous physically distinct portion of a system that is seperated from other portions of the system by bounding surfaces

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1 Phase – F=2 – Bivariant

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2 Phases – F=1 – Univariant

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3 Phases – F=0 – Invariant

The entropy of a pure crystalline substance is zero at absolute zero because the crystal arrangement must show the greatest orderliness at this temperature

CONDENSED SYSTEMS •

S & L phases only

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the vapor state is disregarded with an assumption of working at a pressure at 1atm o 2 Components – liquid phases o 2 Components – S & L – eutectic mixtures o 3 Components

Two Component System Containing Two Liquids •

Binodal Curve – area within the curve which represent a 2 phase system

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Upper Consolute/Critical Solution Temperature – max. temperature at which two phase region in the phase diagram of a two-component system containing two liquids will exist

Lorenzo Dominick Cid 2015

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Tie line o o

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Sedimentation line from which a system seperates into phases of constant composition approximates proportion of components in a particular temperature

Conjugate Phases o phases of constant composition that separate when a mixture is prepared within the boundary of the 2phase system

Two Component System Containing Solid and Liquid •

Eutectic Point o minimum temp. where both exist in liquid form o point where solid A, solid B & the liquid phase coexist

Three Component System

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Andreasen apparatus

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↑ Sedimentation rate = ↑ Particle size (direct proportionality)

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follow the Stoke’s Law

Particle Size Determination •

Coulter Counter

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HIAC/Royco

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Gelman Counter

Derived Properties Porosity of Voids •

Porosity – measure of a void volume in a powder material

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Bulk Volume – total volume of the material

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Void Volume – difference between bulk and true volume

Density

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Ternary system

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True Density – density of actual particle

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2 liquids that are miscible + 3rd component (co-solvent) with affinity to both layers

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Granule Density – volume of particles together with intraparticulate spaces

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has 4 degrees of freedom

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Bulk Density o mass of powder divided by the bulk volume o USP Method 1 – Graduated Cylinder o USP Method 2 – Scott Volumeter o USP Method 3 – Vessel

MICROMERITICS •

study of small particles

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Fundamental properties o defined individually o Ex. particle size & shape, particle size distribution, surface area

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Flow Properties •

Derived properties o computed o dependent on fundamental properties o Ex. Porosity, Density, Flow properties, Packing arrangement

Particle Size Determination Optical Microscopy

Angle of Response o maximum angle possible between the surface of a pile of power and the horizontal plane ℎ 𝑡𝑎𝑛𝜙 =   𝑟 h = height of cone r = radius of base cone o

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↑ AOR = ↑ Flow Property

Tapped Density o measured using a tapped density tester by repeated tapping until a consistent tapped volume is achieved

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microscope

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individual particles can be seen

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tedious and 2D image is only seen

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Ferret Diameter – measure of the distance between tangents parallel to some fixed directions

LIQUIDS

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Projected Area Diameter – diameter of a circle with the same area of the particle

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less kinetic energy than gases

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occupy definite volume

Martin Diameter – length of the line that bisects the particle

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take the shape of contaniners

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denser than gases

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not compressible

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Sieving •

use of sieves

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official method – USP Method

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mesh number refers to number of openings per inch

Solutions of Electrolytes & Non-Electrolytes True Solutions

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↑ Mesh Number = ↓ Particle Size (inverse proportionality)

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molecular dispersions

Lorenzo Dominick Cid 2015

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particle size =