Physical Pharmacy I - States of Matter Lecture Notes PDF

Physical Pharmacy I States of matter Lect. Israa saad Mustafa Second stage, first semester Department of Pharmacy /Al-Kunooze University College 2 The ideal gas law 3 R = 0.08205 liter atm/mole K so the volume in liter 5 ...

Physical Pharmacy I States of matter Lect. Israa saad Mustafa Second stage, first semester Department of Pharmacy /Al-Kunooze University College 2 The ideal gas law 3 R = 0.08205 liter atm/mole K so the volume in liter 5  Gas particles move due to internal kinetic energy üThe particles exhibit continuous random motion owing to their kinetic energy. üThe average kinetic energy, E. is directly proportional to the absolute temperature of the gas. 𝟑 E= ⁄𝟐 𝑹𝑻 6 ² Molecular weight of ideal gas g P.V = RT mwt 7 The van der Waals Equation for Real Gases Real gases composed of molecules of a finite volume that tend to attract one another (like attractive van der Waals forces) so Both the Pressure and the Volume will be affected. a/V2 is the Internal pressure per mole resulting from the intermolecular attraction forces between molecules. b is accounts for the incompressibility of the molecules that excluded from volume. 8 Liquid state 9  Liquid state 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. Liquids are considerably denser than gases and occupy a definite volume 10  Liquid state 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: is the temperature above which it is impossible to liquefy gas irrespective of the applied pressure. Critical pressure : pressure required to liquefy a gas at its critical temperature. 11 Liquid state Critical temp. of water is 374 C (647 k) at 218 atm. Critical temp. of Helium is -267.95 C (5.2 k) at 2.26 atm. The critical temperature is considered as rough measure of attractive forces between molecules. Above critical temp. no amount of pressure can bring molecules within the range of attraction force and cause the atoms or molecules to cohere together. The high critical values for water result from the strong dipolar forces between the molecules and particularly the hydrogen bonding that exists. 12  Because of VDW interaction forces liquid considers denser than gas and occupy a definite volume. At critical pressure the liquid has the highest vapor pressure. Only the weak London force attracts helium molecules, and, consequently, this element must be cooled to the extremely low temperature of 5.2 K before it can be liquefied. Above this critical temperature, helium remains a gas no matter what the pressure. 13 Methods of achieving liquefaction Subject the gas to intense cold (by the use of freezing mixtures). Adiabatic expansion in a vacuum, flask, which effectively insulates the contents of the flask from the external environment., in which we have cooling occur due to the work of expansion on the expense of its own heat energy content (collision frequency). Joule-Thomson effect: expansion of a highly compressed into a region of low pressure causes cooling. Due to expending of energy in overcoming the cohesive forces of attraction between molecules. Precooling the gas before expansion may enhance liquefaction. 14  Pharmaceutical application of liquified gases: aerosols Aerosols are solution dosage form of drug dissolved or dispersed in a liquefied gas (propellants) under high pressure in closed container ( below critical temp.) Upon release of the pressure by spraying outside chamber, liquid convert to gas and the gas expands and spray drug particles. Propellants are chlorofluorocarbon, hydrofluorocarbons, Nitrogen and CO2. The pressures within the container ranging from 1 to 6 atm at room temperature. Gaseous phase and liquid phase within the container at room temperature. 15 The containers are filled either by cooling the propellant and drug to a low temperature within the container, which is then sealed with the valve, or by sealing the drug in the container at room temperature and then forcing the required amount of propellant into the container under pressure. In both cases, when the product is at room temperature, part of the propellant is in the gaseous state and exerts the pressure necessary to extrude the drug, whereas the remainder is in the liquid state and provides a solution or suspension vehicle for the drug. 16  Vapor pressure of liquids The liquid molecules have different kinetic energies (or different velocities) at a given temperature, then the molecules with highest energies break away from the surface of the liquid and pass into the gaseous state (vapor), and some of the molecules subsequently return to the liquid state (condensation). 17 Vapor pressure of liquids When the condensation rate equals the vaporization rate at a definite temperature, the vapor becomes saturated and a dynamic equilibrium is established. The pressure of the saturated vapor above the liquid is then known as the equilibrium vapor pressure. As the temperature of the liquid is elevated, give more energy and more evaporation, increase vapor pressure. If the temperature of liquid is increased and pressure is constant or pressure is decreased and the temperature is constant, the liquid will pass into the vapor state. 18 Clausius-Clapeyron equation: Heat of Vaporization ΔHv P2 ΔH v (T2 − T1 ) log = P1 2.303RT1T2 Where p1 and p2 are the vapor pressures at absolute temperatures T1 and T2, and ΔHv is the molar heat of vaporization, that is, the heat absorbed by 1 mole of liquid when it passes into the vapor state (R= 1.987 cal⋅K−1⋅mol−1 ) ΔHv of water at 100 C = 539cal/g ΔHv of water at 180 C = 478cal/g ΔHv of water at ? C = zero cal/g 19  Clausius-Clapeyron equation: Heat of Vaporization ΔHv HOMEWORK R= 1.987 cal⋅K−1⋅mol−1 20  Boiling point Atmospheri Boiling points is affected by the pressure: c pressure B.p. for water is 100 C at 760 mmHg B.p. for water is 97.7 C at 700 mmHg B.p. for water is 20 C at 17.5 mmHg Vapor pressure The boiling point may be considered the the temperature at which thermal agitation can overcome the attractive forces between the molecules of a liquid. Therefore, the boiling point of a compound; like the heat of vaporization and the vapor pressure at a definite temperature, provides a rough indication of the magnitude of the attractive forces. 21  Boiling point B.p. increase with increase in molecular weight of hydrocarbons, alcohols and carboxylic acids ??? “because the attractive van der Waals forces become greater with increasing number of atoms”. Branching cause a decrease in b.p., how??? “Branching of the chain produces a less compact molecule with reduced intermolecular attraction” Ethanol shows higher b.p. than corresponding hydrocarbons? “as a results of H-bond”. Carboxylic acid have abnormal b.p. compare with hydrocarbon of similar no. of atoms ? “because the acids form dimers through hydrogen bonding that can persist even in the vapor state.” 22  Boiling point Carboxylic acid have abnormal b.p. compare with HC of similar no. of atoms ? “because the acids form dimers through hydrogen bonding that can persist even in the vapor state.” Nonpolar substances (the molecules of which are held together predominantly by the London force) have low boiling points and low heat of vaporization. Polar molecules (particularly those such as ethyl alcohol and water, which are associated through hydrogen bonds) exhibit high boiling points and high heat of vaporization. 23 24 The solid state 25  Solid state Crystalline Solids ü Definite shapes and an orderly arrangement of units. ü Uncompressible (similar to liquids) ü Has both Crystalline and amorphous structures ü The structural units of crystalline solids arranged in fixed geometric patterns of lattices. ü Each crystalline structure have definite melting point. ü Crystal habit (morphology) depends on the nature of the molecules and affected by temperature, pressure, type of solvent, salt formation, humidity, etc. 26  Solid state Crystalline Solids The various crystal forms are divided into 6 (7 in some references) distinct crystal systems 1) Cubic like NaCl 2) Tetragonal like Urea 3) Hexagonal like Iodoform 4) Monoclinic like Sucrose 5) Triclinic like Boric acid 6) Rhombic like Iodine 27 28  Solid state Crystalline Solids The binding forces of the crystal may be electrostatic (NaCl), or covalent (graphite), or Van der Waals and hydrogen forces (organic compounds), Increasing binding forces causes an increase in the melting point (Tm). Ionic and atomic crystals are hard and brittle and have high Tm , while molecular crystals are soft and have relatively lower Tm. Metallic crystals (good conductors because of the free movement of the electrons in the lattice) may be soft or hard depends on crystal lattice defects. 29  Solid state Polymorphism: Stable Polymorphic forms? Chemically identical Crystalline vs amorphous? Different Tm, X-ray Diffraction Stable vs metastable and and solubility unstable Metastable Polymorphic forms examples: diamond and graphite 30  Solid state Polymorphism: Materials like many drugs and excipients have more than one crystalline form. Spontaneously transfers from one to another. The formation of polymorphism of a compound may depend on crystallization process: 1. Solvent difference (the packing of a crystal might be different from a polar versus a nonpolar solvent) 2. Impurities (metastable) because of specific inhibition of growth patterns. 3. The level of supersaturation (higher than solubility --- metastable). 4. Temperature of crystallization. 5. Geometry of covalent bonds (rigid or flexible planner structure). 6. Attraction and repulsion of cations and anions. Metastable 7. Pressure. 8. Relative humidity. 31  Solid state: polymorphism: Theobroma oil (cacao butter): It shows 4 polymorphic forms Unstable: γ Tm = 18 C Metastable: α Tm = 20 C β’ Tm = 28 C Stable: β Tm = 34.5 C. It melts to a large degree over a narrow temperature range (34 C–36 C). Upon melting at 35 C cause a complete liquefaction and destroy the nuclei of stable β crystals and not re-crystalize until supercooling at 15 C. The crystals that form are the metastable gamma, alpha, and beta prime forms, and the suppositories melt at 23 C to 24 C or at ordinary room temperature. It is better to prepare the suppositories by melting the base at 33 C. 32  Solid state Polymorphism: 33  Solid state Polymorphism: Cortisone acetate: Two molecules of the polymorph α-carbamazepine As injectable suspension dosage form. joined together by hydrogen bonds. Shows 4 unstable forms in the presence of water and one stable form. Haloperidol, Tamoxifen citrate, Chloramphenicol palmitate, Carbamazepine and Estrogens Enantiotropic transition: the changes of the polymorphic forms one to another is reversible. Monotropic transition: When the transition takes place in one direction only- for example, from a metastable to a stable 34  Solid state Solvates (pseudopolymorphs): Residual solvent upon crystallization (cocrystals vs solvates) Solvates vs hydrates It affects crystallization by effect on intermolecular attractive forces 35 Amorphous Solids: Solid state The molecules are arranged in random manner as in liquid state as results of super- cooled liquid, has more water solubility than crystalline form. Why? They do not have definite Tm. They have glass transition temperature (Tg) Amorphous substances, as well as cubic crystals, are usually isotropic, that is, they exhibit similar properties in all directions. Crystals other than cubic are anisotropic, showing different characteristics (electric conductance, refractive index, crystal growth, rate of solubility) in various directions along the crystal. Beeswax and paraffin, although they appear to be amorphous, assume crystalline arrangements when heated and then allowed to cool slowly. Petrolatum contains both crystalline and amorphous constituents (semicrystalline). Example: The crystalline form of the antibiotic novobiocin is poorly absorbed and has no activity, whereas the amorphous form is readily absorbed and therapeutically active. This is due to the differences in the rate of dissolution. 36 How can you characterise polymorphism? Solid state 37  X-Ray Diffraction X-rays are a form of electromagnetic radiation having a wavelength on the order of interatomic distances (about 1.54 Å for most laboratory instruments using Cu Kα radiation; the C—C bond is about 1.5 Å). X-rays are diffracted by the electrons surrounding the individual atoms in the molecules of the crystals. The x-ray diffraction pattern on modern instruments is detected on a sensitive plate arranged behind the crystal and is a “shadow” of the crystal lattice that produced it. Using computational methods, it is possible to determine the conformation of the molecules as well as their relationship to others in the structure. This results in a full description of the structure including the smallest building block, called the unit cell. 38  X-Ray Diffraction Qualitative vs quantitative analysis by x-ray diffraction ?? Different polymorphs give different crystallography. It can be used to differentiate between solvates and true polymorphs by changing the temperature. Amorphous compounds have no definite peak in X-ray spectra. 39  X-Ray Diffraction Lack of a change in the powder x-ray diffraction patterns at the different temperatures is a strong indication that the form is not really solvated, or minor changes may indicate a structure that maintains its packing motif without the solvent preset. Powder X-ray patterns of (a) amorphous, and (b) crystalline sucrose. 40