States of Matter PDF

States of matter Menna Magdy  States of matter Liquid Gases Liquids solids crystalline...

States of matter Menna Magdy  States of matter Liquid Gases Liquids solids crystalline Solid state Liquid state Gaseous state *Intermolecular (Vander Intermolecular forces Intermolecular forces of Waal and H-bonding)  Van der Waal forces attraction in gases are *Interatomic (covalent and  Hydrogen bonding non-existent Ionic forces). Fixed shape and volume Fixed volume but NOT No definite shape or fixed shape volume Particles are immobile BUT Molecules are mobile in Molecules move in can only vibrate. three axes straight paths at all perpendicular to one directions at high another velocities  Gases Molecules in the gaseous state move along straight paths, in all directions, at high velocities ➔ COLLISIONS occur with other molecules or walls of container ➔ This process is responsible for the pressure of the system. At room temperature there is no intermolecular force of attraction and has no order. Gas is easily compressed while liquid and solid is incompressible The volume of gas is usually expressed in liters or cubic centimeters. The temperature involved in gas equations is given in absolute or Kelvin degrees (°K). "Zero ° C = 273.15 °K)".  Gases Volume (V), pressure (P), & absolute temperature (T) of gas are interrelated by general ideal gas law: PV = nRT n: number of moles of gas & R: molar gas constant (0.08205 liter. atm/mole. Deg K). Sublimation ➔ Conversion from the solid to the gaseous state without melting due to high vapor pressure, e.g. Iodine and camphor Deposition ➔ Recondensation of gas into solid state.  → The conditions 0 0C and 1 atm are called standard temperature and pressure (STP). 1 atm ≈ 760.001 mm-Hg T = 0 0C = 273.15 K PV = nRT P = 1 atm V = n RT P Molar gas constant: = 0.08205 liter.atm/mole. K  is a substance that is a liquid or solid at room temperature and that passes into the gaseous state when heated to a sufficiently high temperature, such as, menthol and ethanol which are vapor at sufficiently high temperature. is a substance that exists in the gaseous state even at room temperature, such as oxygen and carbon dioxide.  Liquids  Particles of liquids are tightly packed but are far enough apart to over one another  intermolecular force is sufficient to give some order arrangement  liquid have an indefinite shape and a definite volume liquefaction of gases is physical conversion of a gas into a liquid state (condensation).  when a gas is cooled it loses some of its kinetic energy in the form of heat and the velocity of molecules decreases  if pressure is applied to gas, the molecules are brought with the effect of the vander waals interaction and pass into liquid state  The transitions from a gas to a liquid and from a liquid to a solid depend not only on the T, but also on the P to which the substance is subjected.  because of these forces liquids are considerably denser than gases and occupied a definite volume Solids may exist in CRYSTALLINE or AMORPHOUS forms The units that constitute the crystal structure can be ions, atoms, or molecules: IONS ATOMS MOLECULES E.g. Cubic NaCl Diamond & Graphite naphthalene CRYSTALLINE SOLIDS AMORPHOUS SOLIDS Structural units are arranged in Molecules are arranged in a random fixed geometrical patterns or manner (considered supercooled lattices. liquids). Have definite shape and order They do not have geometrical shape arrangement of units Cubic (sodium chloride). Glass ➔ convert to crystalline state after long period of time. Crystalline Novobiocin ➔more Amorphous Novobiocin ➔ less stable→less energy→ less soluble→ stable→more energy→ more poorly absorbed ➔ has poor soluble→ well absorbed ➔ has high activity activity  Amorphous solids also differ from crystalline solid in: (1) Not having a definite MP (2) Flow under pressure. (3) Not have polymorphs Amorphous substance & cubic crystals are isotropic (exhibit similar properties in all direction). Other crystals are anisotropic (showing different characters : electric conductance, refractive index in various direction of crystal). Characterization of Crystalline Materials: a. X-Ray Diffraction: Reflection of X-ray beam from atomic planes of crystal ➔ structure of crystal is investigated. b. Differential scanning calorimetry (DSC) ➔ Melting Point Differential scanning calorimetry (DSC) is a thermoanalytical technique in which the difference in the amount of heat required to increase the temperature of a sample and reference is measured as a function of temperature. Both the sample and reference are maintained at nearly the same temperature throughout the experiment. DSC is a thermodynamical tool for direct assessment of the heat energy uptake, which occurs in a sample within a regulated increase or decrease in temperature DSC is a versatile method that is used to determine alterations in structural properties of a sample as a function of time and temperature.  Freezing point The temperature at which liquid passes into solid It is also the melting point The temperature at which the pure liquid and solid exist in equilibrium at external pressure 1 atm (sometimes known as the normal freezing point or normal melting point) Latent heat of fusion The heat absorbed when a gram of solid melts or the heat liberated when it freezes for water at 0 ºc = 80 cal/gram Heat of fusion is considered as heat required to increase interatomic or intermolecular distance in the crystal, thus melting occur. Crystals of weak bonding force has low melting point and low heat of fusion Crystal of strong bonding force has high melting point and high heat of fusion c. Polymorphism: Polymorphs ➔ Substances existing in more than one crystalline form. They are chemically identical but differ in melting points, X-ray diffraction patterns, and solubility. Examples: *Carbon (Diamond & Graphite) *Ice: Ice has 15 known crystal structures which exist at various temperatures and pressures. *Cacoa butter (We should use only stable β form) Cacoo butter is natural fat consists mainly of a single glyceride, it melts to a large degree over a narrow temperature range (34-36°C). It shows different crystalline forms depending the degree of heating, the cooling process, and on conditions during this process. 1) α form → unstable polymorph (melting at 22°C) 2) prime β form → Metastable polymorph (melting at 28 °C) 3) β- stable form → stable polymorph (melting at 34.5°C ) 4) γ form → Unstable polymorph (melting at 18 °C)  Significance of polymorphism: 1- Polymorphs exhibit different solubility. For slightly soluble drugs it affect rate of dissolution so one polymorph may be more active than the other of the same drug. Examples Chloramphenicol palmitate can exist in three polymorphs: A, B, C 1) A → Stable polymorph (poor solubility) 2) B → Metastable polymorph (more soluble than A) 3) C → Unstable polymorph (freely soluble)  On the solubility, rate of dissolution, and biological availability of the drug Plasma profiles of Chloramphenicol palmitate from oral suspensions containing the forms A, B, and A:B (50:50) 2- Suspension Cortisone acetate exist in 5 different forms 4 unstable (in presence of water) & change to stable form. This transformation produce caking of crystals. For suspension formulation the stable form must be used to prevent cake formation. Tamoxifen citrate can exist in two forms A ---< Metastable polymorph (more soluble) B ---< Stable polymorph (poor solubility) An ethanolic suspension of polymorph A spontaneously rearranges into polymorph B. factors affecting interconversion between polymorphs 1- Heating 2- Grinding under water 3- Suspension in water  Unstable Energy Stable Stable Metastable ❑ Higher stability (lower E). ❑ Lower stability (higher E). ❑ Lower solubility. ❑ Higher solubility. Metastable Stable Stable Crystal growth ↑solubility ↓solubility 70 µg/ml 50 µg/ml Suspension/cream  Liquid Crystalline State: Fourth state of matter intermediate between the liquid and solid states called mesophase. They are intermediate states of mobility and rotation. Mobile and have the Birefringent (a property of flow properties of crystals) ➔ light passing through liquids material is divided into two components with different refractive indices) Properties of Liquid Crystals Liquid crystals have intermediate nature ➔ some of liquid properties and some of solids.  Types of liquid crystalline materials: Smectic Nematic. (Soap or grease - like) (thread - like) Molecules mobile in 2 Molecule mobile in 3 direction direction. Rotate about 1 axis Rotate about 1 axis. N.B. A third type (cholestiric) considered as a special case of nematic They have a helical chiral structure Smectic has the most pharmaceutical significance why? as it forms ternary mixture: Surfactant, water & weakly amphiphilic or nonpolar additives.  The liquid crystalline state may result either from: Heating of the solid ➔ Thermotropic liquid crystals Action of certain solvents on solids ➔ Lyotropic liquid crystals N.B. The first thermotropic liquid crystal was made by Friedrich by heating solid cholesteryl benzoate at 145°C ➔ turbid liquid (liquid crystal), 179°C ➔ clear (conventional liquid state) Significance and Uses of liquid crystals: Some liquid crystals show color changes with temp. ➔ used to detect areas of elevated temp. under skin that may be due to a disease process (liquid crystal thermometer→ safer than mercurial thermometer).  Some liquid crystals are sensitive to electric fields →used in developing display systems Liquid Crystal Display (LCD). Use to solubilize insoluble drug (smectic SAA) Increase the viscosity so stabilize emulsion and suspension (emulsifying and suspending agent) Approaches to the improvement of aqueous solubility: 1. Cosolvency 2. pH controls 3. Micellar Solubilization (conc. of SAA > CMC) 4. Complexatlon 5. Chemical modifications 6. Particle size control 7. Solid dispersion  Solid dispersion 26 Water insoluble Water soluble drug carrier Solid dispersion In vivo dissolve Molecules or Small drug particles  Solid dispersion 27 Solid dispersion 1. Eutectics 2. Polymeric amorphous solid dispersion (PASD)  1. Eutectics Liquid A Melting Liquid B point of A Melting point of B Temperature Liquid solution (A + B) Solid A Liquid solution Solid B (A + B) Liquid solution Solid A Solid B (A + B) Eutectic Eutectic temperature point Solid A + Solid B A A B A B A B B 2 Eutectic A (100%) Composition 8 B (100%)  1. Eutectics Examples of eutectic derived formulations 29 Eutectic mixtures are one way to mix a poorly soluble compound with a highly soluble compound, to aid in the dissolution of the poorly soluble compound (If A is highly water soluble and B poorly soluble, in principle A will rapidly dissolve releasing fine crystals of B (API) ) The eutectic combination of chloramphenicol/urea and sulphathiazole/urea serve as examples for the preparation of a poorly soluble drug in a highly water soluble carrier. Melting them together Molten mixture Water insoluble Water soluble drug carrier Solidification In vivo Solid dispersion  2. Polymeric amorphous solid dispersion (PASD) by Hot melt extrusion (HME) 1. mixing of drug with 4. Extrusion of ▲ polymer the melt to form a 3. Mixing solid dispersion. of the melt 2. Melting Increasing the temperature above the melting point of the polymer to produce a 30 melt  2. Polymeric amorphous solid dispersion (PASD) 31 A polymeric amorphous solid dispersion (PASD) is a formulation technology in which the API is dissolved and/or dispersed in a a carrier (polymer). The API can be maintained in an amorphous form in a PASD, avoiding polymorph transitions. ) Crystallization Incorporation of an amorphous drugs into a polymer matrix network hinders the molecular mobility of the drug to help maintain the amorphous  The Distribution of Solutes Between Immiscible Liquids: Co Oily Cw Aqueous Distribution or partition coefficient (K) partition coefficient (oil to water) partition coefficient (water to oil) 𝑪𝑶 𝑪𝒘 K K o/w = K w/o = 𝑪𝒘 𝑪𝒐 For example, a partition coefficient of 2 for a solute distributed between oil and water may also be expressed as a partition coefficient between water and oils of 0.5.  Co Octanol log p p = K O/W = 𝑪𝑶 Cw Aqueous 𝑪𝒘 (Hydrophilic > Lipophilic) (Hydrophilic = Lipophilic) (Hydrophilic < Lipophilic) 𝑪𝑶 𝒍𝒐𝒈 𝒑 = 𝒍𝒐𝒈 𝑪𝑶 𝑪𝑶 𝑪𝒘 𝒍𝒐𝒈 𝒑 = 𝒍𝒐𝒈 = 𝒍𝒐𝒈 𝒑 = 𝒍𝒐𝒈 𝑪𝒘 𝑪𝒘 log p = -ve log p = +ve log p = 0 log p < 0 log p > 0