PharmSci Exam 2

1) Ionic Interactions: association btw charged molecules i.e. btw negative and positive ions2) Van der Waal Forces: association btw uncharged molecules; the larger the mol. wt., the stronger the interaction. Three Types: ~Dipole-Dipole (Keesom forces) ~Dipole-Induced dipole (Debye forces) ~Induced dipole-induced dipole (London forces)3) Ion-Dipole4) Ion-induced dipole5) Hydrogen bonds

~high kinetic energy=molecules move fast in all directions>>gases exert Pressure~Weakest intermolecular forces~Gases are compressible~Relevant pharmaceutical dosage form: Aerosols~Aerosols are products that are packaged under pressure and contain therapeutically active ingredients that are released upon activation of an appropriate valve systemEXamples: aerosol inhalers (very fine liquid droplets travel deep into the alveoli; Antiseptics (minimize irritation to damaged skin; Local anesthetics

~Stronger intermolecular attractive forces than gases (weaker than solids)~Lower kinetic energy than gases~Characterized by their vapor pressures (VP) and their boiling points (BP)

~At equilibrium, the pressure of the vapor above the liquid is called the vapor pressure~The stronger the intermolecular forces, the lower the number of molecules that can escape, the lower the vapor pressure

General Rules~non polar molecules have lower BP than polar molecules because the non polar molecules are held together only by the weak London forces -high molecular weight>>>stronger van der Waal interactions>>>higher BP -Branching of molecules>>>decreased degree of order>>>weaker interactions>>>lower BP~Polar molecules have high BP because strong polar interactions can exist (e.g. H bond in water)

Great intermolecular (interatomic) attractive forces~lowest kinetic energy~characterized by their melting points: the stronger the intermolecular forces, the higher the melting point~can be crystalline or amorphous

~units are arranged in fixed geometric patterns or lattices~have sharp well defined melting points so can tell if substance is pure~e.g. ice and sodium chloride~A large crystal is formed by translations of a much smaller unit called the "unit cell"; in NaCl crystals, the unit cell is cubic in shape

~Random arrangement of units~considered supercooled liquids because molecules are arranged somewhat as in the liquid state; they tend to flow over a period of time when subjected to sufficient pressure~do not have definite melting points and melt over a temperature range~e.g. glass and plastics

~Polymorphic compounds can crystallize in more than one crystal form~the different crystal forms result from different possible arrangements of the molecules in the crystal~the different crystal forms have different physical properties e.g. solubility and melting point~Ex) carbon (diamond and graphite)
Polymorphism in Pharmaceuticals~some drugs are polymorphic i.e. crystallize in more than one crystal form~the different crystal forms have different physical properties (solubility, melting point..etc.) which may have an impact on the biological activity~Form II of the sulfameter is more active orally in humans than form III (arranged so polar groups are buried inside)

Cortisone acetate exists in at least 5 different crystalline forms:~4 of the 5 forms are unstable in water and convert to the 5th stable form when prepared in aqueous suspensions~conversion to the stable form is accompanied by caking~therefore, cortisone acetate suspensions should be prepared using the stable form to prevent caking

~Cacao butter is a triacylglycerol that crystallizes in four different forms: alpha, Beta, Beta', and gamma~each form has a different melting point~the most stable form is the Beta form and melts at 34.5 degrees C (close to body temp, solid at room temp)~in preparing cacao butter suppositories, do not melt the base completely and leave a small unmelted portion to preserve nuclei of the stable form

~Usually the amorphous form is more soluble, hence more effective~Example) Novobiocin (antibiotic) -the crystalline form (polar groups are burried) has low solubility>>>poor absorption>>>therapeutically inactive -Amorphous novobiocin has high solubility>>>well absorbed>>>therapeutically active

~changes in the state of matter depends on the nature of forces holding the molecules together~Liquid to gas: increased mol.wt. increased intermolecular forces, increased BP, decreased VP~Solid to Liquid: Increased mol.wt., increased intermolecular forces, increased MP, decreased solubility

~A phase is a consistent, physically distinct segment of a system that is separated from other segments of the system by binding surfaces.~For multiphase systems, equilibrium is achieved only in closed systems~the existence of each phase in multiphase systems is determined by variables such as temperature, pressure, concentration...etc.~to describe a system, we need to define a number of variables.~the minimum number of variables to be defined can be calculated using Gibbs' phase rule

~Gibbs' phase rule: the number of degrees of freedom in a system at equilibrium is equal to the number of components minus the number of phases plus the constant 2~F=C-P+2~F is the number of degrees of freedom i.e. the least number of variables (pressure, temp...etc) that we need to define in order to describe the system~C is the number of components in the system e.g. if the system contains ice, water and water vapor the number of components is 1 because they all have the composition H₂O~P is the number of phases in the system e.g. if the system contain ice, water and water vapor the number of phases is 3