Module 5 Physical Pharmacy

PHYSICAL PHARMACY ------------------------------------------------------------------------

PHYSICAL CHEMISTY – branch of chemistry concerned with physical properties and structure of matter and with laws and theories of physical and chemical changes

PHASE DIAGRAM F

PHYSICAL PHARMACY – application of physical chemistry in pharmacy; study of physicochemical properties of substances used in drug formulation

B A

PRESSURE

I. FORCES OF ATTRACTION A. INRAMOLECULAR – intra (within) the molecule  Ionic Bond – transfer of electrons; metal (electron donor) + non-metal (electron acceptor); (ex. Na: p+ = 11; e- = 11 -> p+ = 11; e- = 10  charge = +1) o PERIODIC TRENDS REPRESENTING BONDS  Ionization Energy – energy required remove electron (low M; high NM)  Electronegativity – ability to attract electrons (low M; high NM)  Covalent Bonds – sharing of electrons; non-metal + nonmetal; polarity – difference in electronegativity (symmetrical = non-polar) o Polar – unequal sharing of electrons; dipole moment – (ex. H α+-Brα-) o Non Polar – equal sharing of electrons (ex. Br-Br) B. INTERMOLECULAR – inter (between) the molecules  Van der Waals o Dipole-Dipole  P + P; Keesom Forces; orientation effect o Dipole-Induced Dipole  P + NP; Debye Forces; inductive effect o Induced Dipole-Induced Dipole  NP + NP; London Forces; dispersive effect  Ion-Induced Dipole  ion + NP I2  NP (solubility – 1:2950) I2 + NaI/KI (solubilizing agent)  I3 + I2 = increase solubility  Hydrogen Bond – hydrogen atom + electronegative atom (N, O, F)

E

D

High T – High P  point B – liquid High T – Low P  point C – gas Point D – Triple Point Point E – Critical Point (minimum temperature and pressure; Critical Liquid (Point F) C

TEMPERATURE

GAS STATE:  Kinetic Molecular Theory o Gases are composed of small particles called atoms; total volume is negligible in relation to space where they are confined o Particles do not attract one another but move with complete independence o Particles exhibit continuous random motion owing to their kinetic energy o Gases exhibit perfect elasticity (no energy exchange)

II. GAS LAWS  at standard temperature (Kelvin = oC + 273) and pressure (1atm = 760mmHg or torr; 76cmHg; 1.01325x106 dynes/cm2; 1.01325x105 Pa or N/m2; 01325 bar)  Boyle’s Law – constant temperature; increase P = decrease V; inversely related 1 𝑃 ∝ 𝑉 * density = increase altitude; decrease volume; P 1V1=P2V2  Charles’ Law – constant pressure; increase T = increase V 𝑇1 𝑉1 𝑇1 𝑇2 𝑇 ∝𝑉; = 𝑜𝑟 = 𝑇2 𝑉2 𝑉1 𝑉2 * H2O – 1.0g/mL  4oC  Gay Lussac’s Law  constant volume 𝑃1 𝑇1 𝑃1 𝑃2 𝑃 ∝𝑇; = 𝑜𝑟 = 𝑃2 𝑇2 𝑇1 𝑇2 o * 121 C – 15-20psi

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© MANOR REVIEW CENTER NOTES (K.L)

 Avogadro’s Law  





𝑉1 𝑛1 𝑉1 𝑉2 𝑉 ∝ 𝑛 (𝑚𝑜𝑙𝑒𝑠) ; = 𝑜𝑟 = 𝑉2 𝑛2 𝑛1 𝑛2 Combined Gas Law 𝑃1𝑉1 𝑃2𝑉2 = 𝑇1 𝑇2 Ideal Gas Law 𝑔 𝑃(𝑀𝑊) 𝑃𝑉 = 𝑛𝑅𝑇 → = 𝐿 𝑅𝑇 𝑔𝑅𝑇 𝑀𝑊 = 𝑃𝑉 o P = pressure (atm) o V = volume (L) o n = moles (gram/MW) o R = universal gas constant (0.08205 L-atm/mole-Kelvin) o T = temperature (K) Dalton’s Law of Partial Pressure 𝑃𝑡 = 𝑃1 + 𝑃2 + 𝑃3 + ⋯ 𝑃𝑛 𝑆𝑦𝑠𝑡𝑒𝑚 = 𝐺𝑎𝑠 𝐴 + 𝐺𝑎𝑠 𝐵 𝑃𝑡 = 𝑃𝐴 + 𝑃𝐵 𝑃𝐴 = 𝑋𝐴 (𝑚𝑜𝑙𝑒 𝑓𝑟𝑎𝑐𝑡𝑖𝑜𝑛) ∗ 𝑃𝑡 𝑛𝐴 𝑃𝐴 = (𝑃 ) 𝑛𝐴 + 𝑛𝐵 𝑡 𝑛𝐵 (𝑃 ) 𝑃𝐵 = 𝑛𝐴 + 𝑛𝐵 𝑡 Clausius Clapeyron Equation – Absolute Temperature α P 𝑃2 ∆𝐻𝑣 (𝑇2 − 𝑇1) log ( ) = 𝑃1 2.303(𝑅𝑇1𝑇2) o P = pressure (atm or mmHg) o T = temperature (K) o R = universal gas constant (8.314 joules/n-K  SI unit or 1.987 cal/n-K  non-SI unit) o ∆Hv = latent heat of vaporation o Latent Heat – amount of energy needed to convert one phase to another per mole of the compound (joules/mole)  ∆HF = latent heat of fusion (melting); solid ↔ liquid  ∆Hv = latent heat of vaporation (evaporation); liquid ↔ gas  ∆Hs = latent heat of sublimation; solid ↔ gas

S

L

G + Heat

III. MICROMERITICS - micro (small); meritics (measure) – study of small particles A. PARTICLE SIZE  METHODS: o Sieve Analysis – USP method (official method); utilizes a series of standard sieves calibrated by National Bureau of Standards; involves size classification followed by weight determination of each fraction  Mesh Number/Size – number of square opening per linear inch; increase mesh number = decrease particle size GIVEN: 100g Mesh Number Grams of powder that did not pass 20 15g 40 25g 60 10g 80 35g CP 15g 1. What percent of the powder is greater than mesh number 60? (did not pass  60) 15𝑔 + 25𝑔 + 10𝑔 = 50𝑔 50 𝑥 100 = 50% 100 2. What percent of the powder is less than mesh number 60? (did pass) 35𝑔 + 15𝑔 𝑥 100 = 50% 100𝑔 3. What percent of the powder is less than mesh number 40 but greater than 80? (did pass  40; did not pass  80) 10𝑔 + 35𝑔 𝑥 100 = 45% 100𝑔 o Optical Microscopy – most accurate; microscope eyepiece is fitted with a micrometer where the diameter can be measured  UNITS: micrometer/micron (µm or µ) = 10-6 m, 10-4 cm, 10-3 mm milimicron (mµ) = 10-9 m = 1 nanometer  3 TYPES OF DIAMETER: for asymmetrical particle) Martin’s – bisect particle Ferret’s – longest, tangeant Projected Area of Circle – area  assumed to occupy diameter of particle

- Heat

 Raoult’s Law – vapor pressure lowering; Po1 (pure solvent) > P1 (solution) + solute = lowered vapor pressure o ∆𝑉𝑃 = 𝑃1𝑜 − 𝑃1 o ∆𝑉𝑃 = 𝑋𝑠𝑜𝑙𝑢𝑡𝑒 (𝑃1𝑜 ) o 𝑃1 = 𝑋𝑠𝑜𝑙𝑣𝑒𝑛𝑡 (𝑃1𝑜 )

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A B C

© MANOR REVIEW CENTER NOTES (K.L)

o Stokes’ Law – sedimentation rate 𝑑2 (𝜌𝑠 − 𝜌𝑜 )𝑔 𝑉𝑒𝑙𝑜𝑐𝑖𝑡𝑦 = 18𝜂  Velocity = sedimentation rate  d = diameter  Ps = density of suspensoid  Po = density of medium  g = gravity  η = viscosity  Andreason Apparatus 𝑑= √

𝑣𝑒𝑙𝑜𝑐𝑖𝑡𝑦 𝑥 18𝜂 (𝜌𝑠 − 𝜌0 )𝑔

o Automated Particle Canter  Coulter Counter – electric resistance  Hiac Rayco – light blockade B. DENSITY

𝑚𝑎𝑠𝑠 𝑣𝑜𝑙𝑢𝑚𝑒 Unit – g/mL (solid and liquid); g/L (gases) Absolute Density – determined in vacuum Apparent Density – determined in air Specific Gravity – higher spg = at the bottom 𝜌=

   

𝑠𝑝𝑒𝑐𝑖𝑓𝑖𝑐 𝑔𝑟𝑎𝑣𝑖𝑡𝑦 =

𝑤𝑒𝑖𝑔ℎ𝑡 𝑜𝑓 𝑠𝑢𝑏𝑠𝑡𝑎𝑛𝑐𝑒 𝑤𝑒𝑖𝑔ℎ𝑡 𝑜𝑓 𝑒𝑞𝑢𝑎𝑙 𝑣𝑜𝑙𝑢𝑚𝑒 𝑜𝑓 𝑠𝑡𝑎𝑛𝑑𝑎𝑟𝑑

𝑠𝑝𝑒𝑐𝑖𝑓𝑖𝑐 𝑔𝑟𝑎𝑣𝑖𝑡𝑦 =

𝜌𝑠𝑢𝑏𝑠𝑡𝑎𝑛𝑐𝑒 𝜌𝑠𝑡𝑎𝑛𝑑𝑎𝑟𝑑𝑠

 STANDARDS: o Solid and Liquid – H2O o Gas – air or hydrogen o Temperature – 25oC; alcohol – 15.56oC o Methods:  Solid Hydrostatic Balance Method Pycnometer Method/Specific Gravity Bottle Method Graduated Cylinder Method Immersion of Solid in Transparent Liquid of Same Density  Liquids Pycnometer Method – leach pycnometer  thermometer Floatation Method - Hydrometer - Mohr-Westphal Balance Monometrick Method – Fischer Davidson Gravitometer C. POROSITY – percent voids  TYPES OF VOLUME: o True Volume (Vp) – volume of particle without spaces o Granular Volume (Vg) 𝑉𝑔 = 𝑉𝑝 + 𝑖𝑛𝑡𝑟𝑎𝑝𝑎𝑟𝑡𝑖𝑐𝑢𝑙𝑎𝑟 𝑠𝑝𝑎𝑐𝑒 o Bulk Volume (Vb)

 TYPES OF POROSITY: o Intraparticular Porosity 𝑉𝑔 − 𝑉𝑝 𝑉𝑔 o Interpartiicular Porosity 𝑉𝑏 − 𝑉𝑔 𝑉𝑏 o Total Porosity 𝑉𝑏 − 𝑉𝑝 𝑉𝑏 D. FLUIDITY – angle of repose (θ)  θ < 30o  free flowing; θ > 40o  + flow enhancer (glidant); low height compared to spreadability = good flowing characteristic ℎ𝑒𝑖𝑔ℎ𝑡 𝑡𝑎𝑛𝜃 = 𝑟𝑎𝑑𝑖𝑢𝑠 E. COMPRESSIBILITY  Carr’s Index 𝑉𝑜 − 𝑉𝑓 𝑥 100 𝑉𝑜 NOT COMPRESSIBLE COMPRESSIBLE NOT POSSIBLE

𝐶𝑎𝑟𝑟 ′ 𝑠 𝐼𝑛𝑑𝑒𝑥 = 0 = Vo = Vf 1-99 = Vo > Vf 100 = Vf = 0  Hausner’s Ratio

𝑉𝑜 𝑉𝑓 NOT COMPRESSIBLE COMPRESSIBLE NOT POSSIBLE

𝐻𝑎𝑢𝑠𝑛𝑒𝑟 ′ 𝑠 𝑅𝑎𝑡𝑖𝑜 = 1 = Vo = Vf >1 = Vo > Vf <1 = Vo < Vf

IV. POLYMORPHISM AND HYDRATES  Cocoa Butter – suppository base o α – 22oC o β – 34.5oC o β’ – 28oC o ȣ - 18oC  Insulin o Short Acting – 100% amorphous o Intermediate – 30% amorphous : 70% crystalline o Long Acting – 100% crystalline  Hydrates – contain water of crystallization  Solubility – HYDROUS < ANHYDROUS LIQUID STATE  Critical Temperature – temperature above which a liquid can no longer exist  Critical Pressure – pressure required to liquefy gas at its critical temperature  Boiling Point – temperature at which vapour pressure of liquid equals atmospheric pressure

𝑉𝑏 = 𝑉𝑝 + 𝑖𝑛𝑡𝑟𝑎𝑝𝑎𝑟𝑡𝑖𝑐𝑢𝑙𝑎𝑟 𝑠𝑝𝑎𝑐𝑒 + 𝑖𝑛𝑡𝑒𝑟𝑝𝑎𝑟𝑡𝑖𝑐𝑢𝑙𝑎𝑟 𝑠𝑝𝑎𝑐𝑒 𝑉𝑏 = 𝑉𝑔 + 𝑖𝑛𝑡𝑒𝑟𝑝𝑎𝑟𝑡𝑖𝑐𝑢𝑙𝑎𝑟 𝑠𝑝𝑎𝑐𝑒𝑠 PAGE 3 OF 7

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SOLID STATE  Crystalline Solid – solid whose structural units are arranged in fixed geometric patter; have definite melting point; have definite shape and widely arrangement of units  DISTINCT CRYSTALS BASED ON SYMMETRY o Cubic – NaCl o Tetragonal – urea o Rhombic – iodine o Hexagonal – iodoform o Monoclinic – sucrose o Triclinic – H3BO3 POLYMORPHISM – ability to exist in more than one crystalline form; different melting point, x-ray crystal and diffraction pattern  Enantiotropic – change is reversible  Monotropic – change is irreversible  Amorphous Solids – supercooled liquids; arranged in random manner; no definite melting poing o + cubic  isotropic – similar in all directions o + others  anisotropic – similar in one direction  Le Chatelier’s Principle – system at equilibrium readjust so as to reduce effect of extended stress o Concentration – forward and backward reactions; reactions go towards less concentration o Pressure – favors side where there is least number of gas mole o Temperature – endothermic (R + ∆  P; increase temp = forward; decrease temp = backward) and exothermic reactions (R  P + ∆; increase temp = backward; decrease temp = forward) o Catalyst – no effect MESOPHASE – liquid crystals; between solid and liquids  Thermotropic – heating of solids  Lyotropic – action of solvent to solids  TYPES: o Sinectic – soaplike or grease like; 2 direction o Nematic – threadlike; 3 direction  Cholesteric – special type  Cholesteryl benzoate – first synthesized liquid crystal THERMODYNAMICS – deals with quantitative relationship of interconversion of various forms of energy  TYPES OF SYSTEMS: o Open – energy and matter exchange o Closed – energy exchanged o Isolated – no exchange  LAWS: 1. Law of Conservation of Energy – energy can be transformed but cannot be created nor destroyed 2. Refers to probability of occurrence of process based on tendency of a system to approach a state of energy

3. Entropy (natural tendency of a process to occur) is zero at absolute zero

V. SOLUBILITY AND Ksp  Solubility 𝑎𝑚𝑜𝑢𝑛𝑡 𝑜𝑓 𝑠𝑜𝑙𝑢𝑡𝑒 (𝑔) 𝑎𝑚𝑜𝑢𝑛𝑡 𝑜𝑓 𝑠𝑜𝑙𝑢𝑡𝑖𝑜𝑛 (𝑚𝐿 𝑜𝑟 𝐿)  Molar Solubility (s) 𝑎𝑚𝑜𝑢𝑛𝑡 𝑜𝑓 𝑠𝑜𝑙𝑢𝑡𝑒 (𝑚𝑜𝑙𝑒𝑠) 𝑎𝑚𝑜𝑢𝑛𝑡 𝑜𝑓 𝑠𝑜𝑙𝑢𝑡𝑖𝑜𝑛 (𝑚𝐿 𝑜𝑟 𝐿)  Solubility Product Constant (Ksp) – product of molar solubility of each component raised to an exponent equal to its stoichiometric coefficient o Capital-element  small coefficient 𝑎𝐴 + 𝑏𝐵 ⇌ 𝑐𝐶 + 𝑑𝐷 𝐾𝑠𝑝 = [𝐶 𝑠]𝑐 [𝐷 𝑠]𝐷 o 2 SPECIES 𝑁𝑎𝐶𝑙 → 𝑁𝑎+ + 𝐶𝑙− 𝐾𝑠𝑝 = [1 𝑠]1 [1 𝑠]1 𝐾𝑠𝑝 = 1𝑠1 1𝑠1 𝐾𝑠𝑝 = 1𝑠 2 𝑆 = √𝐾𝑠𝑝 o 3 SPECIES 𝐵𝑎𝐶𝑙2 → 𝐵𝑎+2 + 2𝐶𝑙− 𝐾𝑠𝑝 = [1 𝑠]1 [2 𝑠]−2 𝐾𝑠𝑝 = 1𝑠1 4𝑠 2 𝐾𝑠𝑝 = 4𝑠 3 3 𝐾 𝑠𝑝 𝑆= √ 4

o 4 SPECIES 𝐴𝑙𝐶𝑙3 → 𝐴𝑙+3 + 3𝐶𝑙− 𝐾𝑠𝑝 = [1 𝑠]1 [3 𝑠]3 𝐾𝑠𝑝 = 1𝑠1 27𝑠 3 𝐾𝑠𝑝 = 27𝑠 4 4 𝐾 𝑠𝑝 𝑆= √ 27

VI. COLLIGATIVE PROPERTIES  dependent on the numerical concentration than the nature  Osmotic Pressure – pressure that resist osmosis o Osmosis – movement of water from high concentration solvent to a lower concentration solvent through a semipermeable membrane; movement of water from low solute to high solute concentration through a semipermeable membrane o Van’t Hoff Equation  Non-Electrolytes: 𝜋 = 𝑀𝑅𝑇  Electrolytes: 𝜋 = 𝜄𝑀𝑅𝑇

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 Vapour Pressure Lowering – + solute = lower VP o Raoult’s Law ∆𝑉𝑃 = 𝑃1𝑜 − 𝑃1 ∆𝑉𝑃 = 𝑋𝑠𝑜𝑙𝑢𝑡𝑒 (𝑃1𝑜 ) 𝑃1 = 𝑋𝑠𝑜𝑙𝑣𝑒𝑛𝑡 (𝑃1𝑜 )  Boiling Point Elevation – + solute = increase Tb Δ𝑇𝑏 = 𝑇𝑏𝑠𝑜𝑙𝑢𝑡𝑖𝑜𝑛 − 𝑇𝑏 𝑜 𝛥𝑇𝑏 = 𝑚𝐾𝑏 o Kb – Ebulloscopic Constant = 0.52oC/molal o m – molality  Freezing Point Depression – + solute = lowering Tf Δ𝑇𝑓 = 𝑇𝑓 𝑜 − 𝑇𝑓𝑠𝑜𝑙𝑢𝑡𝑖𝑜𝑛 𝛥𝑇𝑓 = 𝑚𝐾𝑓 o Kf – Cryoscopic Constant = 1.86oC/molal o m – molality

3. Step 1 – Step 2 4. ** Step 3 / Evalue o Class II – addition of solvent; hypertonic  isotonic  White Vincent Method – addition of water to make solution isotonic, followed by addition of isotonic or isotonic-buffered solution to make solution to its final volume 𝑉𝑜𝑙𝑢𝑚𝑒 𝑜𝑓 𝐻2 𝑂 = 𝑤𝑡𝑑𝑟𝑢𝑔 𝑥 𝐸𝑣𝑎𝑙𝑢𝑒 𝑥 111.1  Sprowl’s Method – simplification of white Vincent method wherein amount of drug is fixed at 1% of a fluidounce solution 𝑉𝑜𝑙𝑢𝑚𝑒 𝑜𝑓 𝐻2𝑂 = 0.3𝑔 𝑋 𝐸𝑣𝑎𝑙𝑢𝑒 𝑥 111.1

VIII. pH AND BUFFER

VII. ISOTONICITY  for parenteral/ophthalmic  Isotonic Solution – same salt concentration to that of body fluids  Hypotonic Solution – lower salt concentration compared to body fluids; swelling  burst  Hypertonic Solution – higher salt concentration compared to body fluids; shrink  crenate  METHODS: o Class I – addition of solute; hypotonic  isotonic  D Method – Freezing Point Depression Method (Cryoscopic Method); blood = -0.52oC; 1 molal = -1.86oC 𝑀𝑊 10 = % 1.86(𝜄) 0.52 Strong Electrolytes – 100% dissolution; strong acids/strong bases; ɩ = 2 Weak Electrolytes – incomplete dissociation (80%); weak acids/weak bases NUMBER OF IONS ɩ (80%) 2 1.8 3 2.6 4 3.4 5 4.2  Non Electrolytes – do not dissociate; ɩ = 1 STEPS: 1. -0.52oC : 0.9% = D [Tf Drug] : x% 2. 0.9% - Step 1 3. Step 2 x volume of preparation  E Method – NaCl Equivalency Method 𝑔𝑟𝑎𝑚 𝑁𝑎𝐶𝑙 𝐸𝑣𝑎𝑙𝑢𝑒 = 1 𝑔𝑟𝑎𝑚 𝑑𝑟𝑢𝑔 𝜄𝑑𝑟𝑢𝑔 𝑀𝑊𝑁𝑎𝐶𝑙 𝐸𝑣𝑎𝑙𝑢𝑒 = 𝑥 𝜄𝑁𝑎𝐶𝑙 𝑀𝑊𝑑𝑟𝑢𝑔 STEPS: 1.

0.9% NaCl 

2.

g drug x Evalue

0.9𝑔 𝑁𝑎𝐶𝑙 100𝑚𝐿

 Strong Acid/Base 𝑝𝐻 𝑜𝑟 𝑝𝑂𝐻 = − log[𝐻 + 𝑜𝑟 𝑂𝐻 − ] [𝐻 + 𝑜𝑟 𝑂𝐻 − ] = 10−[𝑝𝐻 𝑜𝑟 𝑝𝑂𝐻] 𝑝𝐻 + 𝑝𝑂𝐻 = 14  Weak Acid/Base o Weak Acid – acid constant (Ka) 𝑝𝐾𝑎 = − log[𝐾𝑎] o Weak Base – basic constant (Kb) 𝑝𝐾𝑏 = −log[𝐾𝑏] 𝑝𝐾𝑎 + 𝑝𝐾𝑏 = 14  Henderson Hasselbalch Equation o Weak Acid 𝑆𝑎𝑙𝑡 ) 𝑝𝐻 = 𝑝𝐾𝑎 + log ( 𝑊𝐴 𝑠𝑎𝑙𝑡 ) 𝑝𝐻 = (14 − 𝑝𝐾𝑏) + log ( 𝑎𝑐𝑖𝑑 𝑎𝑐𝑖𝑑 ) 𝑝𝐻 = 𝑝𝑘𝑎 − log ( 𝑠𝑎𝑙𝑡 o Weak Base 𝑊𝐵 ) 𝑝𝐻 = 𝑝𝐾𝑎 + log ( 𝑆𝑎  Buffers – resist change in pH; weak acid + conjugate base; weak base + conjugate acid o Buffer Capacity/Index/Value/Efficiency  Van Slyke Equation 𝐸𝑞 𝑐ℎ𝑎𝑛𝑔𝑒 𝑖𝑛 𝐿 Δ𝑁 → Δ𝑝𝐻 𝑐ℎ𝑎𝑛𝑔𝑒 𝑖𝑛 𝑝𝐻 o PREDOMINATION:  pH < pKa  unionized  pH > pKa  ionized  pH = pKa  maximum buffer capacity

𝑥 𝑣𝑜𝑙𝑢𝑚𝑒 𝑜𝑓 𝑝𝑟𝑒𝑝

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IX. REACTION KINETICS  moles disappearing; moles appearing ZERO FIRST SECOND 𝐶𝑜 − 𝐶𝑡 𝐶𝑜 1 𝐶𝑜 − 𝐶𝑡 1 K (rate ( ) ln ( ) ( ) constant) 𝑡 𝐶𝑡 𝑡 𝐶𝑜 𝐶𝑡 𝑡 0.5𝐶𝑜 t½ 0.693/𝐾1 1/𝐶𝑜 𝐾2 𝐾0 0.1𝐶𝑜 T90 0.105/𝐾1 --𝐾0 1 1 Unit of K 𝑐𝑜𝑛𝑐𝑒𝑛𝑡𝑟𝑎𝑡𝑖𝑜𝑛 𝑡𝑖𝑚𝑒 𝑡𝑖𝑚𝑒 𝑐𝑜𝑛𝑐. 𝑡𝑖𝑚𝑒  Zero Order – constant rate of reaction; independent on amount remaining; suspension; long term stability 𝐾𝒐 = 𝐾1 𝑥 𝑎𝑚𝑜𝑢𝑛𝑡 𝑑𝑖𝑠𝑠𝑜𝑙𝑣𝑒𝑑  First Order – constant fraction; dependent on amount of drug remaining; solution; accelerated stability 𝐶𝑡 = 𝐶𝑜 𝑒 −𝐾𝑡  t ½ - Half Life – time wherein 50% is degraded and 50% remained  t90 – Shelf Life – time wherein 10% of the drug is degraded while 90% ( USP) remained  Expiration Date 𝐸𝑥𝑝𝑖𝑟𝑎𝑡𝑖𝑜𝑛 𝐷𝑎𝑡𝑒 = 𝑀𝑎𝑛𝑢𝑓 𝐷𝑎𝑡𝑒 + 𝑡90

 CLASSIFICATION OF LIQUID ACCORING TO THE TYPE OF FLOW o Newtonian Flow = F α G (ex. water acetone)

G

η

F

G

o Non-Newtonian Flow – non-time; shear dependent  Plastic Flow – Bingham Bodies - associated with flocculated particles - presence of yield value (f) - Yield Value (f) – stress at which flow begins - (ex. ointments, pastes, creams, cataplasm ceratesm butter, margarine)

0f G

X. RHEOLOGY  study of flow; branch of physics which deals with deformation and flow of matter  Absolute Viscosity (η) – internal friction; resistance of a fluid to flow; Unit: poise (ρ) or dynes-s/cm2  Kinematic Viscosity – Unit: stokes 𝑎𝑏𝑜𝑠𝑙𝑢𝑡𝑒 𝑣𝑖𝑠𝑐𝑜𝑠𝑖𝑡𝑦 𝐾𝑖𝑛𝑒𝑚𝑎𝑡𝑖𝑐 𝑉𝑖𝑠𝑐𝑜𝑠𝑖𝑡𝑦 = 𝑑𝑒𝑛𝑠𝑖𝑡𝑦  Relative Viscosity – no unit 𝑎𝑏𝑠𝑜𝑙𝑢𝑡𝑒 𝑣𝑖𝑠𝑐𝑜𝑠𝑖𝑡𝑦 𝑅𝑒𝑙𝑎𝑡𝑖𝑣𝑒 𝑉𝑖𝑠𝑐𝑜𝑠𝑖𝑡𝑦 = 𝑣𝑖𝑠𝑐𝑜𝑠𝑖𝑡𝑦 𝐻2 𝑂  FACTORS AFFECTING VISCOSITY o Gas – ↑ temp, ↑ η o Liquids  ↑ temp, ↓ η  ↓ MW, ↓ η  + electrolytes, ↓ η  + organic substance, ↑ η  Newton’s Law of Flow – the higher the viscosity of liquid, the greater the shearing stress is required to produce a certain rate of shear 𝐹 (𝑠ℎ𝑒𝑒𝑟 𝑠𝑡𝑟𝑒𝑠𝑠) 𝜂= 𝐺

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η

0

f

F

G

 Pseudoplastic Flow – shear thinning behavior; (ex. gums, tragacanth, Na alginate, methyl cellulose); exhibited by polymer in solution 𝐹 (𝑐𝑜𝑛𝑠𝑡𝑎𝑛𝑡) ↓𝜂= 𝐺 ↑

G

η

F

G

© MANOR REVIEW CENTER NOTES (K.L)

 Dilatant Flow – shear thickening behavior; associated

with particles which do not tend to aggregate or stick together; (ex. paint suspension: >50%) 𝐹↑ ↑𝜂= 𝐺 (𝑐𝑜𝑛𝑠𝑡𝑎𝑛𝑡 → 𝑠𝑙𝑜𝑤)

G

η

F

G

o Non-Newtonian – time dependent  Thixotropy – reversible gel-sol; (ex. SiO2, Mg Bentonite, Na Bentonite); through time: ↓η (due to hysteresis) – pseudoplastic  Theopexy – start as pseudoplastic; through time ↑η; (ex. Gypsum paste; synovial fluid)  INSTRUMENTS: o Single Point Viscometer  Capillary Viscometer – Ostwald Saybolt Poiseulle’s Method: 𝑟 5 𝜌𝑡𝜋 𝜂= 8𝑣𝑙  r – radius (cm)  ρ – density (g/cm3)  t – time to flow (s)  v – volume – cm3  l – length – cm  Falling Sphere Visco – Hoppler Visco o Multipoint Viscometer  Cup and Bob Viscometer Searle Type – bob is rotating - Stormer; Haake – rotovisko; Brookfield; Synchroelectric viscometer Cone and Plate – Ferranti-Shirley Viscometer o Others: Penetrometers – ointment  viscoelasticity

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