Properties Of Solutions & Dosage Form Design

Front 1

the relationship of the physical-chemical properties of a drug to its bioavailability, pharmacokinetics, pharmacodynamic and toxicologic effects?

Back 1

biopharmaceutics

Front 2

a drug product that has the same bioavailability as the reference product when administered at the same molar dose of active drug and by the same route of administration?

Back 2

bioequivalence

Front 3

drug products that contain the same active drug in the same chemical form (salt, ester, etc.). The drug products must be the same dosage form, same strength or concentration, and be administered by the same route of administration?

Back 3

pharmaceutical equivalents

Front 4

drug products that are both bioequivalent and pharmaceutical equivalents and that produce the same therapeutic effects?

Back 4

therapeutic equivalents

Front 5

the modeling of movement of a drug's time course within the body and describes the process of drug disposition or ADME?

Back 5

pharmacokinetics

Front 6

relates the concentration at the site of action to the nature and magnitude of the observed effects?

Back 6

pharmacodynamics

Front 7

The PK and PD of a drug determine?

Back 7

relationship between administration of dose and therapeutic response to dose

Front 8

what kind of an approach does pharmacokinetics provide to drug dosing?

Back 8

rational

Front 9

Process by which unchanged drug proceeds from the site of administration to the site of measurement in the body?

Back 9

administration

Front 10

process of reversible transfer of a drug to and from the site of measurement?

Back 10

distribution

Front 11

process of biotransformation from the parent drug to one or more metabolites?

Back 11

metabolism

Front 12

irreversible loss of drug from the site of measurement?

Back 12

elimination

Front 13

the entire dose administered can be accounted for by the drug and its metabolites in various body compartments and as excreted drug or metabolite is an example of?

Back 13

mass balance principles

Front 14

exponential decline in plasma concentration and dependence on distribution and elimination of a drug is indicative of an?

Back 14

IV dose

Front 15

maximum plasma concentrations of a drug?

Back 15

Cmax

Front 16

time to maximum plasma concentration?

Back 16

tmax

Front 17

Cmax, tmax, and AUC are indicative of?

Back 17

oral dose

Front 18

which routes of administration does absorption account for?

Back 18

all extravascular routes (all but IV)

Front 19

what absorption properties need to be considered in relation to movement of drug from administration site into systemic circulation?

Back 19

rate and extent

Front 20

can change gastric emptying, drug stability, dissolution, binding of drugs in the GI tract, and first-pass effect? what does this affect?

Back 20

food/herbal products/drugs, rate and extent of absorption

Front 21

permeability of a drug across lipid bilayers and dissolution of a compound from formulation are both affected by?

Back 21

ionization and lipophilicity

Front 22

driving force for passive diffusion?

Back 22

concentration gradient

Front 23

does not actively participate in absorption?

Back 23

membrane

Front 24

passive diffusion can be?

Back 24

transcellular or paracellular

Front 25

permeability across the membrane is dependent on?

Back 25

size, protein binding, lipophilicity, charge

Front 26

increased lipophilicity (decreased polarity)=?

Back 26

increased permeability

Front 27

higher partition coefficient means?

Back 27

increased partitioning into octanol (lipid) and less into water

Front 28

also remember to consider (?) when thinking about permeability?

Back 28

size

Front 29

only (ionized or non-ionized) compounds cross membranes?

Back 29

non-ionized

Front 30

ionization and permeability for weak acids: ↓ pH (more acidic) → ↑ % HA → ↑ non-ionized →?

Back 30

↑ absorption rate

Front 31

ionization and permeability for weak bases: ↑ pH (more basic) → ↑ % R3N → ↑ non-ionized →?

Back 31

↑ absorption rate

Front 32

ionization and dissolution for weak acids: ↑ pH → ↑ % ionized → ↑ solubility →?

Back 32

↑ dissolution rate

Front 33

ionization and dissolution for weak bases: ↓ pH → ↑ % ionized → ↑ solubility →?

Back 33

↑ dissolution rate

Front 34

physiochemical properties that favor drug dissolution?

Back 34

do not favor permeability across membranes, and vice versa

Front 35

BCS means?

Back 35

biopharmaceutics classification system

Front 36

high solubility & high membrane permeability?

Back 36

generally well absorbed

Front 37

high solubility & low membrane permeability?

Back 37

permeability rate limited absorption

Front 38

low solubility & high membrane permeability?

Back 38

dissolution rate-limited absorption

Front 39

low solubility & low membrane permeability?

Back 39

very poor oral bioavailability and therefore poor absorption

Front 40

proteins incorporated into the lipid bilayer that transport substances from one side of the membrane to another?

Back 40

carrier mediated transport

Front 41

what kind of substances use carrier mediated transport?

Back 41

lipid-insoluble substances that are too large for passive diffusion (i.e. amino acids and sugars)

Front 42

substrate specific, saturable, and subject to inhibition?

Back 42

transporters

Front 43

two types of transporters?

Back 43

uptake or efflux

Front 44

does passive facilitated diffusion require energy?

Back 44

no

Front 45

what does passive facilitated diffusion use as its driving force?

Back 45

concentration gradient

Front 46

no more than an equal concentration can be attained on the receiving side of the membrane in which type of transport?

Back 46

passive facilitated diffusion

Front 47

transport that requires energy?

Back 47

active transport

Front 48

molecules transported against concentration gradient in?

Back 48

active transport

Front 49

examples of primary active transport?

Back 49

Na/K ATPase and drug transporters that use ATP

Front 50

examples of secondary active transport?

Back 50

antiporters and symporters

Front 51

gastric emptying and intestinal motility affects?

Back 51

absorption

Front 52

food affects?

Back 52

absorption

Front 53

other medications and supplements can change absorption via?

Back 53

pH changes, binding to drugs, effects of first-pass metabolism

Front 54

can compliance affect absorption?

Back 54

yes

Front 55

refers the the fraction of the dose administered that reaches systemic circulation?

Back 55

bioavailability

Front 56

accounts for absorption from the gut (or other site of administration) and first-pass effects in the intestine and liver (transport and metabolism)?

Back 56

bioavailability

Front 57

most appropriate parameter to measure bioavailability?

Back 57

AUC

Front 58

measure of total systemic exposure?

Back 58

AUC

Front 59

a measure of the total amount of a drug that reaches systemic circulation from a dosage form compared to a reference standard?

Back 59

relative bioavailability

Front 60

when is relative bioavailability used?

Back 60

when no IV data available

Front 61

what prevents availability of IV formulation?

Back 61

cost, instability, poor solubility, adverse effects, lack of approval

Front 62

can be used to compare the fraction absorbed for different dosage forms, routes of administration, or different conditions?

Back 62

relative bioavailability

Front 63

bioequivalence testing for generics vs. brand drugs?

Back 63

relative bioavailability

Front 64

bioavailability data can be used for determining?

Back 64

quantity absorbed, rate of absorption, duration of drug presence, relationship between levels and efficacy/toxicity

Front 65

what must be either pharmaceutical equivalents or pharmaceutical alternatives (same therapeutic moiety or its precursor, but not necessarily the same amount, dosage form, salt or ester)?

Back 65

bioequivalent drug products

Front 66

To be bioequivalent, two such products must?

Back 66

exhibit similar rates and extents of absorption when same molar dose administered

Front 67

some products may be considered bioequivalent when only? why?

Back 67

extents of absorption are similar, because rate might not be a factor in effectiveness

Front 68

the reversible transfer of drug between the vascular space and the extravascular space?

Back 68

distribution

Front 69

Volume of Distribution (Vd) represents?

Back 69

specific dilution space of the drug in the body

Front 70

different drugs have different volumes of distribution reflecting?

Back 70

tissue distribution vs. plasma concentration

Front 71

blood is 55%?

Back 71

plasma

Front 72

most plasma proteins are?

Back 72

albumin

Front 73

the space between the cells in a tissue?

Back 73

interstitium

Front 74

interstitial fluid make-up?

Back 74

plasma proteins and water

Front 75

how much interstitial fluid in a 70 kg person?

Back 75

~ 9 liters

Front 76

interstitial fluid that carries lipophilic compounds/drugs and is very slow?

Back 76

lymph

Front 77

how much plasma in a 70 kg person?

Back 77

~ 3 liters

Front 78

combination of interstitial fluid and plasma?

Back 78

extracellular fluid (ECF)

Front 79

solutes and fluid found inside cell?

Back 79

intracellular fluid (ICF)

Front 80

volume of total body water in 70 kg person?

Back 80

42 liters

Front 81

range of volume of drugs in humans?

Back 81

3 L (0.04 L/kg) - 1400 L (20 L/kg)

Front 82

not a true physiologic volume?

Back 82

apparent volume of distribution

Front 83

apparent volume (Vd) describes?

Back 83

drug concentration in tissues relative to plasma

Front 84

increased Vd?

Back 84

more distribution into tissues, less in plasma

Front 85

decreased Vd?

Back 85

less distribution into tissues, more in plasma

Front 86

size that easily moves through paracellular gaps of capillaries (except the brain)?

Back 86

MW less than 10,000

Front 87

size that is too large to enter ISF in significant amounts?

Back 87

MW more than 10,000

Front 88

drugs can bind to which two plasma proteins?

Back 88

albumin and alpha-1-acid-glycoprotein

Front 89

well perfused tissues? why is this significant?

Back 89

brain, liver, kidney, heart, more perfusion means better distribution

Front 90

disease states affecting perfusion?

Back 90

hypertension, heart failure, diabetes

Front 91

why is plasma protein binding relevant?

Back 91

only free drug can pass through capillary endothelium

Front 92

binding and accumulation in tissues can affect?

Back 92

distribution

Front 93

which drug state mainly uses paracellular movement?

Back 93

ionized

Front 94

two main processes of elimination of drug from the body?

Back 94

metabolism, excretion

Front 95

chemical transformation of drug into metabolites?

Back 95

metabolism

Front 96

removal of unchanged drug (primarily by via the kidneys)?

Back 96

excretion

Front 97

organs responsible for elimination?

Back 97

liver, kidney

Front 98

metabolism and biliary secretion?

Back 98

liver

Front 99

filtration, secretion, reabsorption?

Back 99

kidney

Front 100

responsible for removal of metabolic waste and for maintaining fluid and electrolyte balance in the body?

Back 100

kidney

Front 101

about how many nephrons per kidney?

Back 101

~ 1 million

Front 102

why is there a gradual decrease in number of nephrons as people age?

Back 102

nephrons cannot regenerate

Front 103

functional subunit of the kidney?

Back 103

nephron

Front 104

urine formation and renal clearance result from three processes?

Back 104

glomerular filtration, tubular secretion, tubular reabsorption

GTT

Front 105

order of renal clearance by anatomy?

Back 105

filtration, secretion, reabsorption

Front 106

for drugs, most clearance occurs at the?

Back 106

glomerulus and proximal tubule (early in the nephron)

Front 107

most important organ for drug metabolism?

Back 107

liver

Front 108

metabolism is important for both?

Back 108

elimination and absorption

Front 109

liver structures that allow for maximum drug intake?

Back 109

sinusoids, hepatocytes

Front 110

the liver removes drugs and other substances from the (?) for metabolism

Back 110

portal vein, arterial blood

Front 111

drugs in the liver can also be secreted into (?) via what mechanism?

Back 111

bile, active transport

Front 112

drugs secreted into the bile are emptied into the?

Back 112

duodenum

Front 113

in the intestines, certain bile salts and lipids (and drugs) are reabsorbed back into the blood through a process called?

Back 113

enterohepatic recirculation

Front 114

elimination of drug from the body is described by?

Back 114

clearance (CL)

Front 115

measure of efficiency of removal of drug by all eliminating organs (metabolism, transport, excretion, etc.)?

Back 115

clearance

Front 116

volume of plasma cleared of drug per unit time?

Back 116

clearance

Front 117

a combination of all elimination process?

Back 117

clearance

Front 118

CL NR means

Back 118

non-renal clearance

Front 119

urine pH affects?

Back 119

renal clearance

Front 120

inhibition of secretion/reabsorption of drugs affects?

Back 120

renal clearance

Front 121

enzyme and transporter inhibition/induction affects?

Back 121

hepatic clearance

Front 122

genetic variability of enzymes and transporters affects?

Back 122

hepatic clearance

Front 123

blood flow, plasma protein binding, disease states all generally affect?

Back 123

clearance

Front 124

minimum drug concentration necessary to cause a pharmacological response?

Back 124

minimum effective concentration (MEC)

Front 125

minimum drug concentration necessary to cause a toxic or adverse response?

Back 125

minimum toxic concentration (MTC)

Front 126

drug concentration range between the MEC and MTC?

Back 126

therapeutic window

Front 127

time from drug administration until the MEC?

Back 127

onset time

Front 128

time that drug concentration remains above the MEC?

Back 128

duration of action

Front 129

amount of drug that produces the desired pharmacological effect in 50% of individuals tested?

Back 129

median effective dose (ED50)

Front 130

amount of drug that produces a defined toxic or adverse effect in 50% of individuals tested?

Back 130

median toxic dose (TD50)

Front 131

ratio between the drug’s median toxic dose and median effective dose; quantifies the relationship between the desired and undesired effects of the drug?

Back 131

therapeutic index (TD50/ED50)

Front 132

defines the optimal drug concentration range for therapeutic success?

Back 132

therapeutic window

Front 133

concentrations below or above therapeutic window will lead to?

Back 133

therapeutic failure

Front 134

MSC means?

Back 134

maximum safe concentration

Front 135

dependent on route of administration, absorption, distribution to target sites, dose, and exposureresponserelationship?

Back 135

time to onset

Front 136

integration of (?) is important?

Back 136

PK and PD

Front 137

after a dose, an effect begins when concentration at target site reaches?

Back 137

a critical value

Front 138

total contribution of atoms in a molecule or components in a solution i.e. molecular weight and mass

Back 138

additive property of solutions

Front 139

depends on structural arrangement of the atoms within a molecule i.e. optical rotation

Back 139

constitutive property of solutions

Front 140

depends on the number of particles in solution i.e. vapor pressure lowering, freezing point depression, boiling point elevation, osmotic pressure

Back 140

colligative property of solutions

Front 141

colligative properties are dependent on?

Back 141

mole fraction (X), molality (m), and osmolality

molarity and osmolarity for convenience

Front 142

disadvantage to molarity?

Back 142

volume changes with temperature and mixing

Front 143

used for theoretical work i.e. development of colligative properties

Back 143

molality

Front 144

you know exactly how much solute and solvent is an advantage of?

Back 144

molality

Front 145

not useful for practical applications since its much easier to measure volume

Back 145

molality

Front 146

X1 + X2 always =?

Back 146

1

Front 147

number of moles of one constituent divided by the total number of moles of both solute and solvent?

Back 147

mole fraction

Front 148

measure of the chemical activity of an electrolyte?

Back 148

equivalent

Front 149

number of equivalents per liter?

Back 149

normality

Front 150

dissolve in water yielding ions?

Back 150

electrolytes

Front 151

do not yield ions in solution?

Back 151

non-electrolytes

Front 152

what to think about when it comes to equivalence?

Back 152

valence

Front 153

solid solute does not exhibit this, only volatile liquids do?

Back 153

vapor pressure

Front 154

causes some molecules of a solvent to leave the solution and enter the vapor phase?

Back 154

escaping tendency

Front 155

what happens to vapor pressure when two liquids are mixed?

Back 155

vapor pressure of each liquid is reduced in proportion to its mole fraction

Front 156

states that vapor pressure of a component (rho) equals the mole fraction of the component in mixture times the vapor pressure of the pure component?

Back 156

Raoult's Law

Front 157

vapor pressure equals external pressure at the?

Back 157

boiling point

Front 158

adding solute (?) vapor pressure and (?) boiling point?

Back 158

decreases, increases

Front 159

kb for water?

Back 159

0.51

Front 160

change in boiling point is proportional to the mole fraction (molality) of (?) in the solution?

Back 160

solute

Front 161

when solute is added to the solution, the escaping tendency and vapor pressure of a solution are (?) and this (?) freezing point?

Back 161

reduced, decreases

Front 162

kf for water is?

Back 162

1.86

Front 163

osmotic pressure principle?

Back 163

solvent follows more solute

Front 164

used to calculate osmotic pressure?

Back 164

ideal gas law

Front 165

R (gas constant) value?

Back 165

0.082

Front 166

celsius to kelvin?

Back 166

add 273

Front 167

n/V = m only in?

Back 167

cases of dilute solutions

Front 168

used to adjust colligative properties for solutions of electrolytes?

Back 168

van't Hoff factor (i)