Porter - Buffers / Complexation / Diffusion Flashcards
Buffer Definition
- 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
-
Resist changes in pH of the solution that they are dissolved
Buffer Action
The resistance to change in pH of a buffer
Blood Buffer
pH range
7.4 pH
maintained by primary buffers in plasma
& secondary buffers in RBC’s
Purposes of Buffers in Pharmacy
Improve Stability
AVOID irritation
Achieve optimum physiological effect
Mimic bio systems
Buffer Composition
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
Debey-Huckel Expression
Used to approximate activity coefficient of a solution
used for solution where IONIC STRENGTH = U is modest
Factors Influencing pH
of a buffer solution
-
Increase Ionic Strength = U
- adding neutral salts to buffer
-
Decrease Ionic Strength = U
- adding WATER
-
Temperature
- can increase or decrease
- EXPERIMENTALLY DETERMINED
Buffer Capacity
weird B
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
Maximum Buffer Capacity
Occurs when
pH = pKa
or
[H3O+] = Ka
Buffer Capacity Range
Buffer solution is useful at a range of
pKa +1 or -1 ph units
generally do not exceed 0.2
Universal Buffer
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
Pharmaceutical Buffers
-
Isotonic buffers:
- Phosphate Buffered Saline
- Sorensen
- Palitzsch/Hind & Goyan
-
Clark-Lubs Mixtures
- KHphthalate
- Gifford = not isotonic
Considerations for PREPARING buffers
- 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
-
LOWER THE BETTER
- Availability & cost of chemicals
- Stability of drugs and buffers
- No Adverse Toxic Effects
Interactions in Solutes
Cation-Anion Interactions
- 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
Interactions in Solutes
Complexation
- 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
Interactions in Solutes
Chelation
- Special type of coordination complex
- Ligand = MULTIDENTATE
- contains 2+ functional groups
- each can interact with substrate
- Ligand = MULTIDENTATE
-
EDTA
- Completely surrounds a metal ion in a cage stucture
Interactions in Solutes
EDTA
- 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
- –> prevent deposition of calcium salts
Interactions in Solutes
y=Carboxyglutamatic Acid
(Gla)
-
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
Interactions in Solutes
Polyions
- 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
Interactions in Solutes
Ion Exchange Polymers
- 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
Hydrophobic Complexation
4 categories
- Pi-Pi Stacking
-
Channel Lattice Complexes
- Bile salts / urea / bentonite
-
Clathrates
- Hydroquinone cage –> traps molecules <4Angs
-
Host-Guest Inclusion Complexes
- Cyclodextrins
Interactions in Solutes
Cyclodextrins
Cyclic polymers of glucose w/ 6-8 glucose monomers
-
Exterior = -OH groups
- water soluble
-
Interior = HydroPHOBIC
-
water is easily displaced by hydrophobic molecules
- = DRUGS
-
water is easily displaced by hydrophobic molecules
Surface Sorption
- Sorption of drugs to surfaces
-
facilitated by ionic / polar interactions
- glass / ressin
-
or hydrophobic interactions
- teflon
-
facilitated by ionic / polar interactions
- Ex. Activated Charcoal
-
adsorbs many substances
- specifically w/ low water solubility
- like toxic alkaloids
- specifically w/ low water solubility
-
adsorbs many substances
Complexation Model
- Identical to models that describe ionization of acids or bases
-
BUT –> in terms of ASSOCIATION CONSTANTS
- not dissociation constants
-
BUT –> in terms of ASSOCIATION CONSTANTS
Diffusion
- Process by which concentration of sulute is
- Reduced by spontaneous flow
- High conc –> low concentration in solution
- ENTROPY OF SYSTEM INCREASES
Fick’s First Law
Flow of Material
vs
Concentration Gradient
- Flux & Diffusivity
- Displacement (inverse)
Diffusivity
(D)
Stokes Einstein Equation
-
INVERSELY PROPORTIONAL TO
-
Molecular Size
- & depends on molecular shape
- Radius
- Viscosity
-
Molecular Size
- Directely proportional to temperature
Factors Affecting Diffusivity
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
- Reducing particle size
