PHAR 523 Exam 1 (Dosage)

Solution

mixture of two or more components that form one homogenous mixture

Solvent (vehicle)

carries the drug into the patient

Solute(s)

molecules dissolved in the solvent (API and excipients)

Drug particle

solid with a particle size and surface area

Active Pharmaceutical Ingredient (API)

part of the drug that is responsible for the health effects.

Dissolution

Process by which a solid solute enters a solution (or amount of drug substance that goes into a solution per unit time under standardized conditions)

Rate of dissolution

how much is dissolved over a fixed amount of time

Solubility

maximum concentration (saturated) of a solute that can dissolve in a solvent at a given temperature

Extent

how much dissolved

How do drugs move across membranes and bind to receptors?

get absorbed into a solution and then they become lipophilic

Saturation solubility

a solution containing maximum amount of solute that can dissolve in a solvent

List the 4 factors that affect solubility

Pressure, temperature, solvent, other solute molecules in solution

solute-solute interaction

the removal/separation of a solute molecule from a solid state (will require energy)

solvent-solvent interactions

separation of the solvent molecules in order to form a cavity (required energy)

solute-solvent interactions

the insertion of the solute molecule into the cavity produced by the solvent (releases energy)

unsaturated solutions

bulk solution, most pharmaceutical systems are unsaturated

super saturated

solution that contains more solute that can dissolve at a given temperature (see precipitates)

Heat of solution

the net amount of heat energy that is absorbed or released when a solute dissolved in a solvent

Endothermic

Absorbs heat (feels cold)

Exothermic

Releases heat (feels warm)

List the 3 types of dissolution

Endothermic dissolution, exothermic dissolution, temperature independent dissolution

Endothermic dissolution

less energy is released when water bonds to the solute than it takes to separate the solute (energy decreases)

Exothermic dissolution

More energy is released when water bonds to the solute than it takes to separate the solute (energy increases)

Temperature independent dissolution

heat is not released or absorbed (solubility isn’t affected by temperature changes)

List the factors that affect solubility

molecular size, chemical substitutions, solid state structure, and melting point/boiling point.

How does molecular size affect solubility?

bigger molecular weight (MW), less soluble

How does melting point/boiling point affect solubility?

If you have a higher melting/boiling point you will have lower solubility (inversely related)

How does chemical substitutions affect solubility?

Higher number of substitutions, the greater the solubility will be.

How does polarity affect solubility?

polar increases solubility, nonpolar decreases solubility

How does solid state structure affect solubility?

Crystalline has low solubility, amorphous as high solubility

crystalline structure

Regular pattern, high stability but low solubility, polymorphism

amorphous structure

disordered arrangement, low stability but high solubility, crystallize overtime

crystalline polymorphs

solids that have more than one crystalline form; stability increases but bioavailability decreases

solvate

drug and solvate molecules associated together in producing a crystal

hydrate

solvate with water as the solvent

The greater the degree of solvation, the

lower the solubility and dissolution rate as compared to the anhydrous form

What are the 3 dosage forms of solvents?

topicals, oral, or injections

Lipophilic compounds

compounds that dissolve in nonpolar solvents

semipolar solvent

falls between polar solvent and nonpolar solvent (capable of dissolving both polar and nonpolar)

cosolvents

solvents used in combination to increase a solute’s solubility

Pharmacokinetics

what the body does to the drug

Pharmacodynamics

what the drug does to the body

Fancy term for drug efficacy and toxicity

pharmacodynamics

bioavailability

subcategory of absorption and is the fraction (%) of an administered drug that reaches the systemic circulation

When is bioavailability 100%?

via IV injection

First pass effect

concentration of drug is greatly reduced before it reaches systemic circulation (occurs in liver mainly but also gut; bioavailability decreases)

Cmax

highest concentration of drug in the blood measured after a dose (typically happens a few hours after dose given)

Tmax

time of peak plasma concentration (Cmax) on the curve

Area under the curve (AUC)

overall amount of the drug in the bloodstream after a dose

Cmin

lowest concentration of the drug in the blood that is measured after a dose (happens right before receiving the usual dose)

t1/2

amount of time it takes to eliminate half of any drug from the body (important PK measure for showing how often a drug must be dosed)

Steady state

when a person is on a drug for a long enough time the concentration no longer builds up in the bloodstream (happens after about 5 half lives)

How do drugs move across a membrane

through a solution

liquid solution

homogenous solution compromised of a solute and solvent

Dissolve

to make or become liquid

Solubility (pt 2)

ability to dissolve in solution

Diffusion layer model

If dissolution is favored, considered soluble; if dissolution is not favored, considered insoluble

rate of dissolution

how fast a molecule moves into a solution

Noyes-Whitney equation

if any terms (excluding h) increase, dissolution increases (direct); if h increases, dissolution decreases (inverse)

How does surface area affect rate of dissolution?

increased surface area means increased rate of dissolution

Micronize

reduce particles to just a few microns in diameter

Saturation solubility (Cs)

concentration of stagnant later (higher Cs, faster dissolution rate)

concentration of bulk solution (Cb)

very close to zero

concentration gradient

Cs-Cb

basic salt form of a weak acid drug

salt form has better dissolution

acidic salt form of a weak base drug

dissolves faster in GI fluid; lower pH increases solubility

why are salts selected?

in order to improve bioavailability, manufacturability, and crystallinability

what happens when stagnant layer (h) gets thicker?

dissolution will decrease

what affects h (thickness)

agitation and viscosity of dissolution medium

Fick’s law

diffusion through the stagnant/diffusion layer determines how fast a molecule dissolves

Rate limiting step of drug dissolution is

diffusion across the stagnant layer (occurs slow)

advantages to increasing dissolution rate

to increase bioavailability (less dose has same effect, which could mean less side effects); alters pharmacokinetics

Ficks law of diffusion

rate of absorption= rate of diffusion

D

diffusion coefficient

S

surface area of membrane at absorption site

K

oil/water coefficient

h

membrane thickness

Ca

drug concentration at absorption site

Cp

drug concentration in plasma

P

permeability coefficient

absorption

passive diffusion across a lipophilic membrane

adsorption

adhesion of dissolved molecules to a solid surface

rate of absorption depends on

concentration gradient, lipophilic character of a drug (Ko/w), surface area of membrane, diffusion coefficient

concentration gradient

difference in the concentration of a substance from plasma to absorption site

Only drug in solution is capable of passing through membranes?

concentration gradient

what is desirable if drug is meant for local use?

low absorption

Class I

high solubility, high permeability

Class II

low solubility, high permeability

Class III

high solubility, low permeability

Class IV

low solubility, low permeability

Major factors governing rate of absorption

dissolution rate, solubility, intestinal solubility

lipophilicity

chemical attraction of a substance to lipid or fat molecules