Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

PHRM 100 – PDD > PDD 02: Drug Release and Dissolution > Flashcards

PDD 02: Drug Release and Dissolution Flashcards

1
Q

Why is dissolution of a drug important?

A

necessary for drug to exert its response

  • drug must be in solution before it can be absorbed, cross membranes, enter cells, and have an effect in the body
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Why is water solubility of a drug important?

A

medium in which drugs must dissolve in the body is usually aqueous

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is a solution?

A

mixture of two or more components that form a single phase that is homogenous down to the molecular level

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is a solvent?

A

determines the phase of a solution

  • usually also constitutes the largest proportion of the system
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is a solute?

A

dispersed as molecules or ions throughout the solvent

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

For weak electrolyte drugs:

What is (intrinsic) solubility (S0)?

A

concentration of solute (ie. un-ionized drug) in a saturated solution in a given solvent at a given temperature (and pressure)

  • S0 = [un-ionized drug]_solution
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is a saturated solution?

A

solute (un-ionized drug) in solution is in equilibrium with solid phase

  • drug_solution ⇆ drug_solid
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is the USP definition of solubility?

A

part(s) of solvent required for one part solute

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

USP Definition of Solubility

What solubility can be formulated as oral solutions? (3)

A
  • very soluble (< 1 parts of solvent for one part of solute)
  • freely soluble (1 to 10 parts of solvent for one part of solute)
  • soluble (10 to 30 parts of solvent for one part of solute)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

USP Definition of Solubility

What solubility requires co-solvent/excipients? (2)

A
  • sparingly soluble (30 to 100 parts of solvent for one part of solute)
  • slightly soluble (100 to 1000 parts of solvent for one part of solute)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

USP Definition of Solubility

What solubility is an alternative dosage form (ie. suspension)? (2)

A
  • very slightly soluble (1000 to 10,000 parts of solvent for one part of solute)
  • practically insoluble (>10,000 parts of solvent for one part of solute)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

For weak electrolyte drugs:

What is total solubility (S)?

A

total concentration of drug (ionized + un-ionized) in solution

  • S = [un-ionized drug]_solution + [ionized drug]_solution = S0 + [ionized drug]_solution
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Total Solubility

Is aqueous solubility of ions or their corresponding un-ionized form greater?

A

aqueous solubility of ions > solubility of corresponding un-ionized form

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Is intrinsic solubility or total solubility greater?

A

total solubility ≥ intrinsic solubility, depending on ionization of the drug (pKa, pH)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What does the intrinsic solubility of a compound/therapeutic agent depend on? (4)

A
  • physicochemical properties of the drug – MW, density, number of rotatable bonds, hydrogen bond donors, hydrogen bond acceptors, etc.
  • solid-state structure of the drug – crystal habit, crystalline/amorphous properties
  • temperature, pressure (only for gas)
  • solvent
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What does total solubility of weak acid and base drugs depend on?

A
  • intrinsic solubility
  • ionization of the solute (pKa, pH of solution)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

How does the solubility of weak acids/bases change as degree of ionization increases?

A

solubility increases as degree of ionization increases

18
Q

What happens to solubility when pH > pKa?

A

solubility of acidic drugs increases

19
Q

What happens to solubility when pH < pKa?

A

solubility of basic drugs increases

20
Q

What is dissolution?

A

process by which a solid phase/substance (ie. tablet, powder, drug, etc.) solubilizes/goes into a solution phase (ie. water)

21
Q

What is often the limiting (or rate-controlling) step in drug absorption?

A

dissolution rate

22
Q

What are the models/theories of drug dissolution? (3)

A
  • diffusion layer model – film theory
  • Danckwert’s model – surface renewal theory
  • interfacial barrier model – double barrier or limited solvation theory
23
Q

What is the diffusion layer model (film theory)?

A
  1. formation of diffusion layer by interfacial reaction – instantaneous
  • solvent molecules replace the drug at the surface
  • drug begins to dissolve at the surface of the solid particle, forming a thin film (diffusion layer) which is saturated with the drug at the solid/liquid interface
  1. diffusion of soluble solute from stagnant layer to bulk of solution – slower, rate-limiting step
  • results in the formation of a concentration gradient, with a high drug concentration in the diffusion layer and a low concentration in the bulk solvent
24
Q

What is the rate of dissolution more frequently determined by?

A

rate of the slower step of diffusion of dissolved solute through the static diffusion layer of liquid that exists at the solid/liquid interface

25
Q

What does the rate of diffusion obey?

A

Fick’s Law of Diffusion

  • D: diffusion coefficient
  • dC/dx: concentration gradient
  • C: concentration
  • x: distance of movement perpendicular to the surface of the barrier
26
Q

What is the rate of dissolution given by?

A

Noyes-Whitney equation

  • D: diffusion coefficient
  • A: surface area of the exposed solid to dissolution medium (undissolved solid)
  • Cs: concentration of the drug at the surface of the solid (ie. the saturated solubility of the drug at the surface of the solid)
  • CB: concentration of the drug in the bulk solution
  • (Cs - CB)/h: concentration gradient
  • k: intrinsic rate constant (D/h)
27
Q

What factors can influence dissolution? (4)

A
  • surface area (A)
  • concentration of drug in bulk solution (CB)
  • intrinsic dissolution rate constant (k)
  • concentration of drug at surface of the solid (CS)
28
Q

How can surface area (A) influence dissolution? (3)

A
  • size of solid particles/surface area
  • dispersibility of powdered solid in dissolution medium
  • porosity of solid particles
29
Q

How can the concentration of drug in bulk solution (CB) influence dissolution? (2)

A
  • volume of the dissolution medium
  • any process that removes dissolved solute from the dissolution medium
30
Q

How can the intrinsic dissolution rate constant (k) influence dissolution? (2)

A
  • temperature
  • thickness of the diffusion layer – agitation, volume of dissolution medium, shape and size of the container, viscosity of the dissolution medium
31
Q

How can the concentration of drug at surface of the solid (CS) influence dissolution? (4)

A
  • temperature
  • nature of dissolution medium – solubility parameters, co-solvents, pH
  • molecular structure of the solute – appropriate selection of drug salt, esterification of the neutral compound
  • MW of the solute
32
Q

What are the formulation methods that enhance/optimize the aqueous solubility of therapeutic agents? (5)

A
  • appropriate selection of drug salt
  • optimization of pH of the formulation
  • addition of co-solvents
  • complexation (with cyclodextrins)
  • addition of surface-active agents (surfactants)
33
Q

What is drug bioavailability?

A

fraction of an administered dose of drug that reaches the systemic circulation

34
Q

What factors does the rate and extent of drug absorption depend on? (3)

A
  • solubility
  • dissolution (rate)
  • permeability (partition coefficient)
35
Q

Partitioning of Drugs and their Distribution

A
  • balance between lipophilicity and hydrophilicity dictates permeability of drug – how quickly it can pass through bilayer
36
Q

What are some applications of the biopharmaceutical classification system (BCS)? (3)

A
  • prediction of in vivo performance (ie. PK) of oral drug product using solubility and permeability
  • in early stages of drug discovery research
  • in pre-clinical and clinical drug development processes
37
Q

Biopharmaceutical Classification System (BCS)

What is class I?

A

high solubility, high permeability

  • ideal for oral route of administration
  • well absorbed (> 90%) because: dissolve rapidly, rapidly traverse the gut wall
  • ie. acetaminophen
38
Q

Biopharmaceutical Classification System (BCS)

What is class II?

A

low solubility, high permeability

  • dissolve slowly, solubility is too low to have completed absorption
  • rapidly traverse the gut wall
  • drugs in this class may require formulation approaches to improve dissolution rate to enhance bioavailability
  • just need to get drug into solution
  • ie. ketoconazole
39
Q

Biopharmaceutical Classification System (BCS)

What is class III?

A

high solubility, low permeability

  • dissolve rapidly
  • unable to permeate the gut wall quickly enough for absorption to be completed
  • drugs in this class may require formulation approaches to improve permeation rate to enhance bioavailability
  • ie. ranitidine
40
Q

Biopharmaceutical Classification System (BCS)

What is class IV?

A

low solubility, low permeability

  • dissolves slowly, solubility is too low for complete absorption
  • poorly permeable across the gut wall
  • both solubility and permeability limitation
  • formulation approaches (prodrug, lipid based drug delivery) may be required
  • ie. amphotericin B

PHRM 100 – PDD (14 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions