Porter - Buffers / Complexation / Diffusion

Question 1

Buffer Definition

Answer 1

• Compounds or mixtures of compounds that
  
  • Resist changes in pH of the solution that they are dissolved
    
    • upon additions of small amounts of acid or base

Question 2

Buffer Action

Answer 2

The resistance to change in pH of a buffer

Question 3

Blood Buffer

pH range

Answer 3

7.4 pH

maintained by primary buffers in plasma

& secondary buffers in RBC’s

Question 4

Purposes of Buffers in Pharmacy

Answer 4

Improve Stability

AVOID irritation

Achieve optimum physiological effect

Mimic bio systems

Question 5

Buffer Composition

Answer 5

Weak Acid + Conj Base/salt

or vice versa

• When dissolved in water it resists large changes in pH
  
  • that would other wise occur w/ addition of small amounts of acid or base

Question 6

Debey-Huckel Expression

Answer 6

Used to approximate activity coefficient of a solution

used for solution where IONIC STRENGTH = U is modest

Question 7

Factors Influencing pH

of a buffer solution

Answer 7

• Increase Ionic Strength = U
  
  • ​adding neutral salts to buffer
• Decrease Ionic Strength = U
  
  • ​adding WATER
• ​Temperature
  
  • can increase or decrease
  • EXPERIMENTALLY DETERMINED

Question 8

Buffer Capacity

weird B

Answer 8

The MAGNITUDE

of the resistance of a buffer to pH changes

aka buffer efficiency / buffer value / buffer index

Increase buffer capacity by

Increasing concentration of buffer components

Question 9

Maximum Buffer Capacity

Answer 9

Occurs when

pH = pKa

or

[H₃O+] = K_a

Question 10

Buffer Capacity Range

Answer 10

Buffer solution is useful at a range of

pKa +1 or -1 ph units

generally do not exceed 0.2

Question 11

Universal Buffer

Answer 11

A mixture of weak acids whose

pkA value DO NOT DIFFER by more than ~2pH units

–> buffer region overlap

WIDE pH range

ex. citric acid / boric acid / DE acid

Question 12

Pharmaceutical Buffers

Answer 12

• Isotonic buffers:
  
  • ​Phosphate Buffered Saline
  • Sorensen
  • Palitzsch/Hind & Goyan
  • Clark-Lubs Mixtures
    
    • ​KHphthalate
• ​Gifford = not isotonic

Question 13

Considerations for PREPARING buffers

Answer 13

• Select a weak acid w/ pkA approx EQUAL to desired pH
• 0.01 < Buffer capacity <0.1
  
  • ​LOWER THE BETTER
    
    • ​less irritation
    • more safe for parenteral solutions
• Availability & cost of chemicals
• Stability of drugs and buffers
• No Adverse Toxic Effects

Question 14

Interactions in Solutes

Cation-Anion Interactions

Answer 14

• Drugs can interact with other ions
  
  • –> inc/decrease solubility
  • change colligative propertios (osmotic)
  • change chemical degradation rate
• pH effects
• LARGE anions/cations -
  
  • -> tend to form ion-pairs

Question 15

Interactions in Solutes

Complexation

Answer 15

• Originally restricted to lewis acid-base reactions
  
  • ​between 2+ chemical constituents
  • Substrate + Ligand = complex
• ​Expanded to cover complexes held together by weaker forces
  
  • Van Der Waals Disperson
  • Dipole / Dipole Interactions

Question 16

Interactions in Solutes

Chelation

Answer 16

• Special type of coordination complex
  
  • Ligand = MULTIDENTATE
    
    • contains 2+ functional groups
    • each can interact with substrate
• EDTA
  
  • Completely surrounds a metal ion in a cage stucture

Question 17

Interactions in Solutes

EDTA

Answer 17

• Used widely in pharmacy to Sequester Metal Ions
  
  • ​copper and iron
• Can complex calcium ions
  
  • –> prevent deposition of calcium salts
    
    • that may precipitate out of solution
  • used as a Antigoagulant with Gla

Question 18

Interactions in Solutes

y=Carboxyglutamatic Acid

(Gla)

Answer 18

• Structurally modified amino acid
  
  • important component of enzymes involved in blood coagulation
  • chelate calcium ions
    
    • = cofacors for coagulation enzymes
• Vitamin K
  
  • ​essential for biosynthesis of Gla

Question 19

Interactions in Solutes

Polyions

Answer 19

• Can interact w/ other drugs to form Poorly soluble complexes
• _​​_Ex. Heparin
  
  • form insoluble complexes w/ many large weakly basic drugs
  • –> incompatabilities (precipitation)
    
    • ​w/ other drugs that are IV administered

Question 20

Interactions in Solutes

Ion Exchange Polymers

Answer 20

• Used in Delivery systems for drugs to:
  
  • ​Reduce volatility
  • Impart stability
  • Mask Taste
  • Improve Bioavailability
    
    • ​by altering physicochemmical properties of drugs
• Ex. Carbopol / polystyrene beads

Question 21

Hydrophobic Complexation

4 categories

Answer 21

• Pi-Pi Stacking
• Channel Lattice Complexes
  
  • ​Bile salts / urea / bentonite
• Clathrates
  
  • ​Hydroquinone cage –> traps molecules <4Angs
• Host-Guest Inclusion Complexes
  
  • ​Cyclodextrins

Question 22

Interactions in Solutes

Cyclodextrins

Answer 22

Cyclic polymers of glucose w/ 6-8 glucose monomers

• Exterior = -OH groups
  
  • water soluble
• Interior = HydroPHOBIC
  
  • ​water is easily displaced by hydrophobic molecules
    
    • = DRUGS

Question 23

Surface Sorption

Answer 23

• Sorption of drugs to surfaces
  
  • facilitated by ionic / polar interactions
    
    • ​glass / ressin
  • or hydrophobic interactions
    
    • teflon
• Ex. Activated Charcoal
  
  • ​adsorbs many substances
    
    • specifically w/ low water solubility
      
      • like toxic alkaloids

Question 24

Complexation Model

Answer 24

• Identical to models that describe ionization of acids or bases
  
  • ​BUT –> in terms of ASSOCIATION CONSTANTS
    
    • ​not dissociation constants

Question 25

**Diffusion**

Answer 25

* Process by which concentration of sulute is * **​*Reduced by spontaneous flow*** * High conc --\> low concentration in solution * **ENTROPY OF SYSTEM INCREASES**

Question 26

**Fick's First Law**

Answer 26

**Flow of Material** **vs** **Concentration Gradient** * **Flux & Diffusivity** * **Displacement** (inverse)

Question 27

**Diffusivity** **(D)** **Stokes Einstein Equation**

Answer 27

* *_INVERSELY PROPORTIONAL TO_* * ***​Molecular Size*** * *& depends on molecular shape* * ***Radius*** * ***Viscosity*** * ***​***Directely proportional to temperature

Question 28

**Factors Affecting Diffusivity**

Answer 28

**_We use these properties to prolong drug action_** * *Slow Diffusion by:* * *​Increasing viscosity* * *Increasing Radius of particle (or both)* * **​Increase Diffusion by:** * ​Reducing particle size * coarse particles diffuse slowly * **Increase Temperature**