Integrated Pharmaceutical Science 1 Physical Pharmacy PDF

IPS1-Physical Pharmacy CENTRO ESCOLAR UNIVERSITY Malolos PHARMACY DEPARTMENT Integrated Pharmaceutical Science 1...

IPS1-Physical Pharmacy CENTRO ESCOLAR UNIVERSITY Malolos PHARMACY DEPARTMENT Integrated Pharmaceutical Science 1 PHYSICAL PHARM ACY This review material is prepared by: Mrs. REGINA ALBERTO-JAZUL I. INTER/INTRAMOLECULAR FORCES INTRAmolecular – forces within the molecule INTERmolecular – forces between molecules to exists as aggregates in gases, liquids, and solids –COHESION, or attraction of like molecules –ADHESION, or attraction of unlike molecules REPULSIVE FORCES Arise when dipolar molecules approach one another close enough “positiv e to positiv e” or “negative to negative”, their electron cloud interpenetrate ATTRACTIVE FORCES Arise when dipolar molecules approach so that the positive pole of one is close to the negative pole of the other TYPES OF INTERMOLECULAR FORCES OF ATTRACTION I. VAN DER WAALS FORCES  Weak forces than covalent bond (50 to 100 kcal/mole) and ionic bond (from 100 to 1000 kcal/mole)  Molecular interactions involved in solubility, complexation, and numerous other physical bonding phenomena  Exist between all atoms and molecules  Critically dependent on the separation distance of the atoms or molecules from each other Three (3) groups of van der Waals forces  Dipole-dipole interaction (Keesom forces)  Between polar molecules; Energy of attraction is 1 to 7 kcal/mole  Examples of substances with permanent dipoles include water, hydrochloric acid, alcohol, acetone and phenol  Induced dipole – induced dipole interaction (London forces) o A polar molecule can produce a temporary electric dipole in nonpolar molecules that are easily polarizable o Energy of attraction is 1 to 3 kcal/mole; Easily polarized molecules include ethylacetate, methylene chloride, and ether  Dipole – induced dipole interaction (Debye induction forces) o Originate from molecular internal vibrations in nonpolar molecules to produce attraction that arises because of synchronized fluctuating dipoles in neighboring atoms o These forces are temporary; Responsible for the liquefaction of gases o The energy of this attractive force is 0.5 to 1 kcal/mole o Exhibited by organic compounds like carbon sulfide, carbon tetrachloride, and hexane II. ION –ION, ION-DIPOLE, AND ION-INDUCED DIPOLE FORCES III. HYDROGEN BONDS - Exist between molecules containing hydrogen atom and a strongly electronegative element II. ST ATES OF MATTER A. G ASES  Molecules travel in random and rapid motion  Gaseous molecules exhibit pressure within confined system (expressed in dynes/cm 2,mmHg, and atm)  Volume of gases is the volume of the container into which it is confined (expressed in L, and cm 3 or mL) KINETIC MOLECULAR THEORY  Gases are composed of particles called MOLECULES.  Particles of gases do not attract one another but rather move with complete independence  Particles exhibit continuous random motion owing to their kinetic energy  The molecules exhibit perfect elasticity THE IDEAL GAS EQUATION The interrelation among volume (V), pressure (P) and the absolute temperature (T) PV = n R T or PV = (g/MW )RT where n is the number of moles (g/MW ) and R is the molar gas constant (0.08205 L-atm/mole-K) PHARMACEUTICAL GASES INCLUDE: 1|Page r.a.jazul/2024 IPS1-Physical Pharmacy Anesthetic gases (nitrous oxide and halothane) Compressed gases (Oxygen for therapy; Nitrogen; Carbon dioxide) Liquefiable gases used as propellants in aerosol products Ethylene oxide used to sterilize or disinfect heat-labile objects VAPORIZATION – phase change from liquid to gaseous state Examples: Ether, halothane, and methoxyflurane used as inhalation anesthetics; Amyl nitrite used as vasodilator SUBLIMATION – solid transform directly to gaseous/vapor state without passing through the liquid state (camphor, iodine) *Intermolecular forces of attraction in gases are virtually non existent at room temperature LIQUEFACTION OF GASES FACTORS AFFECTING THE TRANSITION OF GAS TO LIQUID STATE 1. TEMPERATURE CRITICAL TEMPERATURE - temperature above which a liquid can no longer exist; CT of water is 374 °C or 647 K 2. PRESSURE CRITICAL PRESSURE - Pressure required to liquefy a gas at its critical temperature; The highest vapor pressure that the liquid can have; CP of water is 218 atm; CT and CP of He = 5.2 K and 2.26 atm B. LIQUID INTERMOLECULAR FORCES OF ATTRACTION: Van der Waals forces and Hydrogen Bonding PHYSICAL PROPERTIES OF LIQUID STATE 1. VAPOR PRESSURE - Increases with rising temperature 2. HEAT OF VAPORIZATION – the heat absorbed when liquid passed into v apor state 3. BOILING POINT - the temperature at which the vapor pressure is equals the external or atmospheric pressure  As pressure decreases, the boiling point lowers 4. SURFACE TENSION 5. FLOW PROPERTIES/VISCOSITY SURFACE TENSION  The force per unit length that must be applied parallel to the surface so as to counterbalance the net inward pull  Surface tension decreases with an increase in temperature; Unit: dyne/cm INTERFACIAL TENSION  Is the force per unit length existing at the interface between two immiscible liquid phases  Reflects the extent of the intermolecular forces of attraction and repulsion at the interface; Unit: dyne/cm METHODS OF MEASURING SURFACE / INTERFACIAL TENSION CAPILLARY RISE METHOD  The force of adhesion between the liquid molecule and the capillary wall is greater than the cohesion between the liquid molecules, so the liquid spread over it and rise in the tube DU NOUY RING METHOD  Used to measure surface and interfacial tensions  The principle is based on the force necessary to detach a platinum-iridium ring immersed at the surface/interface is proportional to the surface/interfacial tension. ADSORPTION AT LIQUID INTERFACES  Surfactants are molecules that are adsorbed at interfaces  The other term for surface-active agents is AMPHIPHILE (molecule or ions having certain affinity for both polar and nonpolar solvents). HLB SYSTEM  Used to classify surfactants  HYDROPHILIC (water-loving) amphiphiles have high HLB values  LIPOPHILIC (oil-loving) amphiphiles are having low HLB values ADSORPTION AT SOLID INTERFACES  Takes place from either adjacent liquid or gas phase  The study of adsorption of gases is concerned with; a. Removal of objectionable odor from room and food, b. Operation of gas mask c. Measurement of particle dimension of powders THE SOLID-GAS INTERFACE  ADSORBENT – the material used to adsorb the gas  ADSORBATE – the substance being adsorbed TYPES OF ADSORPTION I. PHYSICAL or VAN DER WAALS ADSORPTION  The adsorbate can be removed from the adsorbent by increasing the temperature (Desorption) 2|Page r.a.jazul/2024 IPS1-Physical Pharmacy II. CHEMICAL ADSORPTION  Irreversible; the adsorbate is attached to the adsorbent by primary chemical bonds SOLID-LIQUID INTERFACE  Dyes, alkaloids, fatty acids, organic acids and bases may be adsorbed from solution onto solids such as charcoal and alumina  Adsorption of diphtheria toxin by various clays  Attapulgite and kaolin adsorb intestinal contents FACTORS AFFECTING ADSORPTION 1. SOLUBILITY OF THE ADSORBATE-The extent of adsorption of a solute is inv ersely proportional to its solubility in the solvent from which adsorption occurs. 2. pH - Adsorption increases as the ionization of the drug is suppressed. 3. NATURE OF ADSORBENT - The extent of adsorption is proportional to the specific surface area. 4. TEMPERATURE - Increase in temperature decreases the amount adsorbed PRINCIPLES WHICH USES SOLID/LIQUID ADSORPTION  DECOLORIZING SOLUTION  ADSORPTION CHROMATOGRAPHY  DETERGENCY-A complex process involving the removal of foreign matter from surfaces  WETTING W ETTING AGENT – a surfactant that when dissolved in water, lowers the advancing contact angle and aids in displacing an air phase at the surface and replacing it with a liquid phase. CONTACT ANGLE – the angle between a liquid droplet and the surface over which it spreads. Applications of Surface Active Agents Emulsifying agents Foaming agents – stabilize gas-in-liquid dispersion Detergents Antifoaming agents – break the foam Wetting agents Antibacterial agents – Quaternary Ammonium compounds Solubilizing agents Aids the absorption of drugs in the body Protective agents RHEOLOGY  Study of flow properties of liquids and the deformation of solids; Also involves the viscosity characteristics of powders, fluids and semisolids VISCOSITY  Resistance to flow of adjacent layers of fluids; Units: in CGS – dyne/sec/cm2 or poise (0.01 poise = 1 centipoise) General categories of flow NEW TONIAN FLOW  Characterized by a constant viscosity, regardless of the shear rates applied  Exhibited by liquids of simple molecules and dilute dispersions NON NEWTONIAN FLOW  Characterized by a change in viscosity characteristics with increasing shear rates NON NEWTONIAN FLOW I. PLASTIC FLOW – “ Bingham bodies”  Does not begin to flow until the shearing stress is exceeded; Exhibited by gels, pastes, creams, ointments, cataplasms, and cerates II. DILATANT FLOW – “ Shear Thickening System”  Viscosity increases with an increase in shear force; Exhibited by suspensions of high percentage of dispersed solids III. PSEUDOPLASTIC FLOW - “Shear Thinning System”  Viscosity decreases with an increase rate of shear; Exhibited by polymers in solution, e.g., natural and synthetic gums OTHER TYPES OF FLOW a. THIXOTROPY – a reversible sol-gel transformation b. ANTITHIXOTROPY – negative thixotropy - increase thickness or resistance to flow with an increase time of shear c. RHEOPEXY – solid forms a gel readily when gently shaken Factors affecting rheological properties and measurement of viscosity of liquids and semisolids include; Temperature Shear rate Pressure Time Measuring conditions Composition and additives C. SOLIDS  The intermolecular forces of attraction are stronger than in liquids or gases  Solids are either crystalline or amorphous CRYSTALLINE AMORPHOUS Fixed molecular order Randomly arranged molecules Distinct melting point Nondistinct melting point Anisotropic (properties are not same in all Isotropic (properties are same in all directions) 3|Page r.a.jazul/2024 IPS1-Physical Pharmacy direction) SIX DISTINCT CRYSTAL SYSTEM CUBIC - Sodium chloride RHOMBIC - Iodine TETRAGONAL – Urea MONOCLINIC - Sucrose HEXAGONAL – Iodoform TRICLINIC - Boric acid BUILDING UNITS OF CRYSTALS 1. ATOMS (diamond and graphite) 3. IONS (Sodium chloride) 2. MOLECULES (Solid carbon dioxide, HCl and naphthalene) POLYMORPHISM o Is the condition wherein substances can exist in more than one crystalline form o Polymorphs may differ in:Melting points, X-ray diffraction patterns and Solubilities Drugs that exhibit polymorphism 1. Theobroma oil  A polymorphous natural fat, melts at 34°-36°C  Has 4 polymorphic forms a. The unstable gamma form – melts at 18°C c. The beta prime form – melts at 28°C b. The alpha form – melts at 22°C d. The stable beta – melts at 34.5°C *If Cocoa butter is heated to 35°C, nuclei of the stable beta crystals are destroyed and the mass does not crystallized until it is supercooled to about 15°C. 2. Estrogens – form crystalline solvates 5. Tamoxifen citrate 3. Spiperone – with two polymorphs 6. Carbamazepine 4. Haloperidol and bromperidol SOLVATES - Crystals containing solvent molecules; Sometimes called pseudopolymorphs Changes that polymorphic forms may undergo (1) Enantiotropic – the change from one form to another is reversible (2) Monotropic – transition takes place in one direction only (Example: metastable to stable form) AMORPHOUS SOLIDS  Molecules are not packed in a repeating long-range ordered fashion  They do not have definite melting points  They tend to flow when subjected to sufficient pressure over a period of time Yield value - force below which the body shows elastic properties Isotropic, as well as cubic crystals Examples include plastics, glass, pitch Changes that polymorphic forms may undergo (1) Enantiotropic – the change from one form to another is reversible (2) Monotropic – transition takes place in one direction only Examples of drugs that exhibit polymorphism 1. Theobroma oil 2. Estrogens – form crystalline solvates D. LIQUID CRYST ALLINE STATE o The 4th state of matter o Characteristics of molecules; Organic, elongated and rectilinear, rigid and possess strong dipoles and easily polarizable groups 2 Main Types 1. SMECTIC ( Soap- or Grease-like)  Molecules are mobile in two directions and can rotate about one axis; Phase that forms in ternary mixtures 2. NEMATIC (Thread-like)  Molecule rotate in one axis but are mobile in three directions; A special case of nematic crystal is cholesteric crystal LIQUID CRYSTAL FORMATION A. Heating of solids – THERMOTROPIC LIQUID CRYSTALS B. Action of certain solvents on solids – LYOTROPIC LIQUID CRYSTALS PROPERTIES OF LIQUID CRYSTALS Exhibit flow properties Possess property of being birefringent Uses/Applications of Liquid Crystals in Pharmacy  To detect areas of elevated temperature due to consistent color change with temperature  In developing display system – nematic type  In the solubilization of water-insoluble materials – smectic mesophase SUPERCRITICAL FLUID  A mesophase formed from gaseous state where the gas is held under combination of temperatures and pressures that exceed the critical point of a substance 4|Page r.a.jazul/2024