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Pharmaceutics 2 Winter Final > 1 - Intro to Biopharmaceutics > Flashcards

1 - Intro to Biopharmaceutics Flashcards

1
Q

What is a membrane? How thick is it? How is it arranged?

A
  • Phospholipid bilayer
  • 10 nm thick
  • Arranged w/ hydrophilic heads on outside and lipophilic chains facing inwards
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2
Q

What is attached to a membrane? Are they attached to the outer or inner side?

A
  • Glycoproteins (protein w/ carbohydrate attached), which may act as ion channels, receptors, intermediate messengers (G-proteins), or enzymes
  • Can be attached to outer or inner sides
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3
Q

Is the structure of a membrane the same in every tissue?

A

No, it changes to allow more specialized functions

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4
Q

Describe the membranes found in capillary endothelial cells

A

Have regions where outer and inner membranes are fused together (called fenestrae) to increase permeability, especially to fluid

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5
Q

Describe the membranes of renal glomerular endothelium

A

Has gaps between cells to allow passage of larger molecules as part of filtration

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6
Q

Describe the membranes of the blood brain barrier

A

Tight junctions between endothelial cells of brain blood vessels to form the BBB and limit passage of polar molecules

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7
Q

What are the methods to cross a cell membrane?

A
  • Active transport using energy (ATP hydrolysis) – usually specific for endogenous molecules, often transports molecules against a concentration gradient
  • Passive transport – most common mode of drug passage through membranes; involves diffusion
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8
Q

What is another name for passive transport across a cell membrane?

A

Transcellular diffusion

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9
Q

What determines the rate of passive diffusion?

A
  • Partition coefficient of the compound
  • Diffusion coefficient of the compound
  • Concentration gradient across the membrane
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10
Q

What are some important chemical properties for membrane binding and diffusion? What other process are these important for?

A
  • Lipophilicity
  • Molecular weight (lower MW is better)
  • Molecular polarity
  • Also important for facilitated transport where a protein channel helps diffusion but doesn’t need energy
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11
Q

What is partition coefficient?

A

How the drug partitions between water and lipid

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12
Q

Which drugs can cross membranes using paracellular transport? (Which chemical properties)

A
  • More hydrophilic
  • Water soluble
  • Low to intermediate molecular weight
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13
Q

Unionized drugs are ___ soluble

A

Lipid

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14
Q

What determines the rate of drug transfer across a lipid bilayer?

A
  • pKa of the drug

- Fraction in the unionized form

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15
Q

What are some factors that influence rate of diffusion?

A
  • Concentration gradient
  • Ionization
  • Lipid solubility
  • Protein binding
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16
Q

What is Fick’s law?

A

Rate of transfer is proportional to the concentration gradient across a membrane

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17
Q

What are some factors that determine the rate of transfer across a concentration gradient?

A
  • Membrane area
  • Concentrations on either side of the membrane
  • Diffusion constant
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18
Q

What determines the diffusion constant?

A

Lipid solubility and molecular weight of the compound

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19
Q

The ____ the molecule, the easier the transfer across a membrane

A

Smaller

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20
Q

What determines degree of ionization of a drug?

A

pKa of drug and pH of environment

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21
Q

What is ion trapping?

A

The rule that an acidic drug will accumulate on the more basic side of a membrane and a basic drug on the more acidic side

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22
Q

Lipid solubility allows a drug to pass through a cell membrane using the ____ pathway

A

Transcellular

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23
Q

Which portion of ADME does lipid solubility affect?

A

Absorption

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24
Q

A molecule w/ a _____ will be permanently ionized

A

Quaternary ammonium

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25
Q

Will a very lipophilic molecule w/ poor water solubility have good or bad absorption? Why?

A

Poor b/c water solubility is the limiting factor in absorption

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26
Q

Can protein bound drugs cross a membrane? What does this mean?

A
  • No, only unbound can cross
  • Increasing plasma concentration of unbound drug will increase rate of transfer across a membrane and accelerate onset of action
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27
Q

Which proteins bind to drugs? What can alter the amount of protein binding?

A
  • Albumin and globulins
  • Protein binding altered in pathological conditions
  • Albumin concentration drops during inflammation
28
Q

What is the biopharmaceutics classification system (BCS)?

A

Framework for classifying drug substances based on aqueous solubility and intestinal permeability

29
Q

Which drugs are included in the BCS? What factors are considered?

A
  • Immediate release oral dosage forms

- Dissolution, solubility, and intestinal permeability determining rate and extent of oral absorption

30
Q

What are the 4 classes of the BCS?

A
  • Class 1 = highly soluble and highly permeable
  • Class 2 = poorly soluble and highly permeable
  • Class 3 = highly soluble and poorly permeable
  • Class 4 = poorly soluble and poorly permeable
31
Q

When is a drug considered highly soluble in the BCS?

A

When the highest dose is soluble in 250 mL of aqueous media over the pH range of the GI tract (1.2-7.4)

32
Q

When is a drug considered highly permeable in the BCS?

A

When absorption (including liver and intestinal first pass metabolism) equals or exceeds 85% of administered dose

33
Q

What is dose solubility volume (DSV)?

A

The highest therapeutic dose (in mg) divided by the solubility of the substance in mg/mL at a given pH and temperature

34
Q

What DSV will allow a drug to be considered highly soluble?

A

DSV equal or less than 250 mL

35
Q

What is a biowaiver? Which classes of drugs can be issued a biowaiver?

A
  • Issued by Health Canada, allows a generic drug to be marketed w/o performing an in vivo bioequivalence study
  • For class 1 or class 3 immediate release oral dose forms
36
Q

What are some rules for biowaivers?

A
  • Sublingual or buccal products not eligible
  • Test and reference product must be the same
  • If coated, must be a non-functional coating (can’t be enteric coated)
37
Q

What are the required conditions for dissolution for bioequivalence?

A
  • Basket (USP 1) or paddle (USP 2) apparatus
  • Basket at 100 rpm; paddle at 50 rpm
  • Dissolution mediate are aqueous buffers at pH 1.2, 4.5, and 6.8
  • Dissolution media volume equal or greater than 900 mL
  • Sampling times 5, 10, 15, 20, and 30 minutes
  • Temperature 37 C +/- 1 C and not less than 12 units per pH medium
38
Q

What is the accepted dissolution result for a class 3 substance?

A

More than 85% dissolved in 15 minutes or less

39
Q

What is the accepted dissolution result for a class 1 substance?

A
  • If very fast dissolving, more than 85% dissolved in 15 minutes or less
  • For all others, more than 85% dissolved in 30 minutes or less
40
Q

What is F2 testing? What is an accepted F2 value?

A
  • F2 = similarity factor
  • Measurement of the similarity in the percentage dissolution between the 2 curves
  • Must be between 50 and 100
41
Q

Most bioavailability studies involve drug measurement in _____ or _____

A

Blood or urine

42
Q

What is assumed when measuring bioavailability?

A

That the drug at the site of action is in equilibrium w/ the quantity of drug in the blood, so blood level is an indirect measure of drug response

43
Q

What is bioavailability?

A

Measure of how much and how quickly drug appears in the blood after administration

44
Q

What can be done to increase onset of action of a drug?

A

Use a dose form allowing rapid absorption and high serum levels

45
Q

When would a slower rate of absorption be desirable?

A

When high serum levels are associated w/ toxicity

46
Q

What is absolute bioavailability?

A

Fraction of dose that reaches the bloodstream

47
Q

What is the range for absolute bioavailability?

A
  • 0-1
  • 0 = no drug is absorbed
  • 1 = entire administered dose reaches the blood
48
Q

What is the total amount of drug reaching the bloodstream proportional to?

A

AUC

49
Q

How is absolute bioavailability calculated?

A
  • Comparison of AUC of oral test product to AUC of dose given intravenously
  • If doses differ, respective AUC values are divided by respective dose
50
Q

What is relative / comparative bioavailability?

A
  • The bioavailability of a test product to a reference standard of the same drug usually at the same dose
  • Determines effects of formulation differences on extent and rate of absorption
51
Q

What are some factors that affect bioavailability?

A
  • Route of administration
  • Formulation factors
  • Physicochemical nature of drug or excipients (if they affect dissolution rate)
  • Px factors
52
Q

Any factor which affects ____ will affect bioavailability

A

Dissolution or absorption

53
Q

Rank the oral dose forms from fastest to slowest availability

A
  • Solutions
  • Suspensions
  • Capsules
  • Tablets
  • Coated tablets
  • Controlled-release tablets
54
Q

What can affect dissolution rate?

A
  • Particle size
  • Crystalline structure
  • Salt or ester form of drug
  • Formulation factors (disintegrants, binders, lubricants, coatings)
55
Q

Which part of ADME does local blood flow affect? Why?

A
  • Absorption rate

- Blood flow continuously maintains concentration gradient needed for passive diffusion across membranes

56
Q

Does first pass metabolism only occur in the liver?

A

No, can also occur in intestines and lungs

57
Q

What does extraction ratio measure?

A

The effect of first pass hepatic metabolism on bioavailability

58
Q

Which meals are most likely to affect GI physiology? What does this mean?

A
  • Meals high in total calories and fat content

- They affect bioavailability also

59
Q

What effect does metoclopramide have on absorption of other drugs?

A
  • Stimulates stomach contraction and generally increases intestinal peristalsis
  • May reduce residence time and Cmax and increase Tmax
60
Q

Which drugs can complex w/ aluminum, calcium, or magensium?

A

Tetracycline and ciprofloxacin

61
Q

A drug w/ poor bioavailability has one or more of the following…

A
  • Poor aqueous solubility
  • Slow dissolution rate in biological fluids
  • Poor stability under physiological conditions
  • Poor permeation through biological membranes
  • Extensive first pass metabolism
62
Q

What are 3 approaches to enhance bioavailability?

A
  • Biological where route of administration or dosage form is changed
  • Chemical modification to increase solubility or permeability (often through formation of pro-drug)
  • Pharmaceutical where formulation is modified, usually to enhance rate and extent of dissolution
63
Q

What is a typical size range of particles?

A

2-5 um

64
Q

When is complexation a useful solubilization technique? Complexation w/ which drug? What is the most common form

A

Complexation w/ cyclodextrins (common form is 1:1 ratio) is useful for drugs w/ lipophilic properties

65
Q

Which class of drugs will have an effect on bioavailability when complexed w/ cyclodextrin?

A

Class 2 and 4 drugs

Pharmaceutics 2 Winter Final (9 decks)

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