Knipp 2

Question 1

coatings

Answer 1

control diffusion rates by modulating release properties

Question 2

solid coatings

Answer 2

protect agent from air/humidy
mask taste
provide special drug release
aesthetics
prevent inadvertant contact w/ drug

Question 3

aqueous coatings

Answer 3

film-forming polymers
plasticizers for flexibility and eslastic
colorant and opafier
vehicle

Question 4

disinigrants

Answer 4

control regions of release based on physiological properties

Question 5

lubricants

Answer 5

can slow dissolution based on properties

Question 6

internal excipients

Answer 6

used to modify the release rate as well: swellable matrices, non-swelling matrices, inert plastics

Question 7

enteric coating

Answer 7

add to dosage form to prevent early release of API.
1. prevent acid sensitive API from gastric fluids
2. prevent gastric distress from the API
3. target API delivery to site in intestine
4. to provide delayed/sustained release
5. deliver API in higher local conc in intestine for better absorption

Question 8

sustained release

Answer 8

pharm dosage form to slow release therapeutic agent such that appearance in systemic circulation is delayed/prolonged. AKA onset pharmalogic action is delayed but therapeutic effect has sustained duration

Question 9

controlled release

Answer 9

goes beyond sustained release and reproducibility/predictability

Question 10

examples of traditional controlled release formulations

Answer 10

coated beads, granules, microspheres: coating on the beads controls release by programmed erosion
multitablet system: small tabs placed in gelatin
microencapsulated: solids, liquids, gases encapped in walled material allowing microparticles across surface
drug embed in slow eroding or hydrophilic matrix: drug is homogenously dispersed in eroding matrix and release is controlled by eosion rate

Question 11

steady state

Answer 11

rate going into the body must be equal to diposition (rate distributed/metabolized/excreted throughout the body)

Question 12

characteristics of drugs best for oral controlled release

Answer 12

either slow/fast rate of absorption/secretion
uniformly absorbed from GI tract
administered in relative small doses
have good safety/therapeutic window
chronic therapies better suited than acute

Question 13

physiological factors affecting absorption

Answer 13

absorbing surface area
residence time at absorption site
pH changes in lumen (unionized will get absorbed)
permeability
dietary fluctuations/effects
complexation/protein binding
biliary uptake and clearance

Question 14

epithelia

Answer 14

predominantly used for external surfaces although endothelial cells are epitheliod
simple squamous
simple columnar
translational
stratified squamous

Question 15

composition of bio membranes

Answer 15

most of surface area
all living cells are enclosed with 1+ membranes
membrane isolates cellular components from environment
cell membrane is semi-permeable membrane, permits rapid passage of chemicals while slowing others
cellular lipid composition is polarized, so outter is different from inner

Question 16

cholesterol effects on membrane?

Answer 16

no. it provides fluidity at lower levels. when exceeds a certain level in membrane, it causes a phase of transition and forms liquid crystalline state. called hardening atherosclerosis when occurs in vasculature

Question 17

intestinal transport mechanisms

Answer 17

passive(non saturable): paracellular (between cells), transcellular (through cells)
carrier-mediated(saturable): active (energy), facilitated diffusion (no energy)

Question 18

general interpretation of caco-2 vs pampa

Answer 18

passive difussion
has linear relationship between active transport and efflux

Question 19

drug transporters

Answer 19

membrane-bound proteins involved in clearance
role is to move important molecules across membranes
crucial determinant of tissue and cellular distribution of drugs
variation can be determinant of drug response
primarily been identified in adults

Question 20

SLC (solute carrier)

Answer 20

43 subfamilies
300 members identified
generally influx or secretory efflux transporters

Question 21

ABCs

Answer 21

7 subfamilies
50 members
generally efflux-multidrug resistant transporters
PgP, MRPs

Question 22

Absorption

Answer 22

many routes of permeation:
influx transport mediated
passive transcellular influx + efflux
passive paracellular
metabolism
efflux of the metabolite

Question 23

conventional terminology

Answer 23

influx: transporters transfer into cells
efflux: transporters pump substrate out of cell back into compartment
absorptive: transporters transfers substrate into systemic blood
secretory: transporters transfer their substrates from blood into bile, urine, GI lumen

Question 24

passive paracellular permeation

Answer 24

hydrophilicity
molecular size + shape
pKa of ionizable groups
linear increase in permeability w/ increasing conc
adjuvants can open tight junctions

Question 25

facilitative/active trans permeation

Answer 25

affinity, Vmax
concentration dependent saturation
expression level
function(drug-drug & drug-nutrition interactions, competitive inhibition)
exicpeints like surfactant can limit effects of efflux by PgP or BCRP

Question 26

GI tract epithelia

Answer 26

oral cavity-buccal
esophagus is comprised of strat squamous
stomach is mainly columnar epithelial w/ mucus goblet cells
small and large intestines have columnar epithelial cells
rectum is best place for absorption w/ simple columnar and strat sqamous epithelia

Question 27

stomach

Answer 27

digest food and control flow into intestine
fast pH is <3
fed pH is 5-7
gastric emptying half-time is ~30 mins
fasted emptying has 4 phases
fed has no cycles

Question 28

stomach anatomy

Answer 28

fundus - contains gas and produces contractions
body - reservoir for ingested food and fluids
antrum - lower part of stomach controls flow into small intestine

Question 29

stomach phases

Answer 29

1) no activity 40-60 mins
2) mixing contractions 40-60 mins
3) stomach: powerful contractions intestine: peristalsis
4) stomach empty of digestible and indigestible food

Question 30

intestine

Answer 30

mouth-anus: 24-32 hrs
most absorption occurs in small intestine
small intestine pH 5-6.5
colon drug absorption mainly occurs in ascending region nearest to SI

Question 31

intestinal surface area

Answer 31

kercking folds
villi
microvilli
all increase SA of SI

Question 32

columnar epithelium

Answer 32

continuous layer of absorptive cells
Crypt region: 3x more crypt than villi, comprised of undifferentiated cells that proliferate. globlet cells-mucus secreting
Villus region: absorptive enterocytes, a few goblet cells do appear. cells from crypt migrate to villus tip and are extruded at tip lifetime of 2-3 days

Question 33

colon characteristics

Answer 33

125 cm from caecum to anus
responsible for water and electrolyte absorption to prevent dehydration and leads to formation of solid fecal matter

Question 34

colon structure

Answer 34

serosa-squamous epithelium covered with adipose tissue
submucosa and mucosa
colonic mucusa: three layers– muscularis mucosae, lamina propria, epithelium
proximinal(ascending) colon is where enteric formulations target by oral admin
distal colon: rectal + suppositories

Question 35

anal muscles with age

Answer 35

as people age, anal muscles slow down their function

Question 36

stomach vs. colon

Answer 36

stomach and colon have inverse relationship with drug concentration. as it decreases in the stomach, it increases in the colon

Question 37

rectum

Answer 37

upper and lower region that transitions to strat squamous.
stratified squamous, non-keratinized allows high drug absorption
lots of high potency drugs that are delivered rectally
gag reflex w/ pills so use suppositories

Question 38

anal absorption

Answer 38

crystalline: form-low solubility
amporphous: increased solubility
free API: potential confounders are food, protein binding, pH, etc.

Question 39

GI characteristics

Answer 39

GI volumes do not correspond with dissolution bath volumes

Question 40

GI transit time variation

Answer 40

gastric residence differs a lot
gastric emptying controls colonic absorption
higher GI residence leads to higher absorption
PT 2 has higher GI so capsule was voided much faster

Question 41

GI transit fed state

Answer 41

capsule was admin 30 mins before breakfast and 4 hrs before lunch but gastric pH and residence changes still occurred

Question 42

characteristics of GI fluids

Answer 42

jejunum: pH 7.08
ileum: pH 7.8
colon: pH 8.1

Question 43

drug solubility changes in GI tract

Answer 43

factors influencing drug solubility:
buffer capacity
bile salts
regional fluids
other drugs
potential issues from endogenous substrates

Question 44

stomach emptying blood flow

Answer 44

stomach>jejunum 1> jejunum 2 > ileum 1> ileum 2> ileum 3> ileum 4> colon
drug diffuses out, gets released, metabolized

Question 45

challenges to assumptions of GI

Answer 45

transporters and enzymes vary in GI
a lot of variability in GI fluid
diet and chemical exposure vary
pharmacogenetics and genomics are issues
inter individual variation
drug-nutrient + drug-drug interactions
gut microbiome
SO ONE SIZE FORMULATION DOES NOT FIT ALL

Question 46

ADMET

Answer 46

Absorption
Disposition: comprised of distribution and elimination
Elimination: describes metabolism and excretion
Toxicity: result of exposure

Question 47

ADME

Answer 47

Absorption, Distribution, Metabolism, Excretion
Drug is dissolved through intestinal tract
Absorbed through portal vein to liver then blood then tissues
Throughout these processes, theres metabolism of drug and excretion of it

Question 48

Nature of pharmacokinetic processes

Answer 48

described by concentration time profiles: shape of profiles depend on conc
compartments represent kinetically similar tissue/space
processes can be reversible or irreversible
processes can be linear or nonlinear
fast and slow processes tend to disappear

Question 49

blood level versus time curve

Answer 49

upward slope is absorption
peak is Cmax + Tmax
after peak is distribution, metabolism, excretion
downward slope is disposition and elimination phase

Question 50

biopharmaceutics terms

Answer 50

bioavailability - rate and extent of drug absorption
absolute bioavailability - AUC of dosage compared to auc of same dose injected intravenously
relative bioavailability - AUC of dosage form compared to arbitrary reference standard
bioequivalent - does not mean therapeutic effects of two dosage forms are equivalent

Question 51

concept and use of dose

Answer 51

amount of chemical in which organism is treated
local concentration of the chemical at the biol response state
relationship between dose and receptor concentration is a function of ADME

Question 52

dosage form design

Answer 52

aborption begins declining as disposition begins to increase
absorption rate Kabs is defined by drug properties of excipients/drug formulation and the physiological barriers between GI and systemic circulation

Question 53

disease plasma levels

Answer 53

plasma levels peak in therapeutic window
prolonged exposure to subtherapeutic doses or ineffective drugs can lead to development of disease becoming worse

Question 54

dose relationship to toxic response

Answer 54

toxic repsonse - blood plasma is toxic level/ MTC
safe and efficacious - blood plasma in therapeutic window/TW
non efficacious - blood plasma not reached therapeutic level/ MEC