Druglikeness

Question 1

Factors Included in Lipski’s rule of 5

Answer 1

Hydrogen Donor Bonds, Hydrogen Bonds acceptor, molecular weight and Log P

Question 2

What Lipki’s Rule of 5 Outlines

Answer 2

Predicts permeability of substance across semi-permeable membrane. A minimum of 2 of these must be met to be orally absorbed. Number may shift depending on admin route and target area

Question 3

Lipinski’s Rule In Relation to H bond donors

Answer 3

< 5

Question 4

Lipinski’s Rule In Relation to H bond Acceptors

Answer 4

< 10

Question 5

Lipinski’s Rule In Relation to Molecular Weight

Answer 5

< 500 Daltons

Question 6

Lipinski’s Rule In Relation To Log P

Answer 6

< 5

Question 7

Example of H bond donors

Answer 7

Water and amide

Question 8

Example of H bond acceptor

Answer 8

Ketone

Question 9

Limitation of LipKini’s Rule

Answer 9

Doesn’t account for dissolution, doesn’t account for drugs with transporters/ pumps and doesn’t evaluate hydrophilicity

Question 10

Biopharmacuetics Classification Systems (BCS)

Answer 10

Measures solubility (hydrophilicity, liberation) and permeability (lipophilicity, absorption). Form of bioequivalence testing (avoids clinical test replication via biowaver, cheaper) and helps in manufacturing process

Question 11

Number of BSC classes

Answer 11

4

Question 12

BCS Class 1

Answer 12

High Aqueous Solubility (fast dosage form liberation) and high permeability (fast absorption). Biowaver granted, low risk

Question 13

BCS Class 2

Answer 13

Low aqueos solubility (slow liberation, rate limiting) and high permiability (fast absorption). No biowaver (risk), most drugs

Question 14

BCS Class 3

Answer 14

High aqueous solubility (fast liberation) and low permiability (slow absorption, rate limiting). Typically not granted biowavers

Question 15

BCS Class 4

Answer 15

low aqueos solubility (slow liberation) and low permiability (slow absorption)

Question 16

BCS High Solubility Def

Answer 16

Highest dose of substance will dissolve <250 ml of water. pH range 1-7.5 at temp 37 degrees Celcius

Question 17

How is high solubility usually referenced calculated

Answer 17

mg amount of solute dissolved per ml of solvent

Question 18

BCS High Permeability Def

Answer 18

Minimum of 90% of substance absorbed in humans. Tested either in animals or in vitro

Question 19

Bioavailability testing in people

Answer 19

Volunteers recieve 1 dose of drug via IV. Plasma drug levels recorded over set time. This is used as reference (straight into circulation = no absorption barriers). Once drug is eliminated from system volunteer recieves oral dose and plasma drug levels monitored over same time. Bioavalaibility = (amount of drug absorbed orally)/(amount of drug absorbed IV)

Question 20

Bioavailability Testing In Vitro Outline

Answer 20

Celll cultures predict permeability in humans by fraction they absorb

Question 21

Permeability Coefficient relationship to rate of flux

Answer 21

Proportional. High coefficient = high flux

Question 22

Relationship between permeability coefficient and concentration on membrane structure

Answer 22

High permeability coefficent = low conc on membrane surface

Question 23

Apparent permeability Coefficent

Answer 23

Numerical estimate of whether drug’s permeability is high/low. >1x10^-5 cm/s is prediction of high permeability

Question 24

permeability coefficient is proportional to

Answer 24

Transport rate and initial donor concentration

Question 25

Permeability coefficient is inveresely proportional to

Answer 25

Surface area exposed

Question 26

What can substitute for apparent permeability coefficent

Answer 26

LogP. 2< LogP < 5 indicates good permeability, regardless of H bond number, pKa and molecular weight

Question 27

BCS Classes in relation to dissolution

Answer 27

To be BCS Class 1, 85% of dosage form must dissolve in 30 mins in 90ml of solvent at pHs 1.2, 4.5 and 6.8, using USPC appaaratus at 37 degrees

Question 28

BCS Functions

Answer 28

Bioequivalence testing between generic and innovator drugs (if same bioavailability granted biowaver, cost and time saving), manufacturing guidance

Question 29

DCS in realtion to BCS

Answer 29

DCS is stricter. Used in the development of oral products as a guideline

Question 30

Ideal BCS Class

Answer 30

class 1

Question 31

How can Class 4 improve both solubility and permeability

Answer 31

Change to structure (eg saltings, crystallisation, solution forming)

Question 32

BDDCS Outline

Answer 32

Substitutes permiability for metabolism. Better understands drug distribution and deposition