Exam 2 Dissolution

Question 1

T or F: Dissolution is defined as the process by which a solid is transformed from aggregates of molecules or ions into a dissolved state (i.e. enters into solution)

Answer 1

True

Question 2

The rate of solution is determined by the rate of _______ of the dissolved substance through a thin layer that forms instantaneously around the solid particles

Answer 2

Diffusion

Question 3

T or F: In the late 1960s, dissolution testing of solid dosage forms became a mandatory requirement for several drugs

Answer 3

True

Question 4

T or F: The dissolution test is a simple and inexpensive measure of the physical consistency of the dosage form being evaluated

Answer 4

True

Question 5

In case of variation in dissolution results, one must investigate the causative sources, which are _________, ________, or ________

Answer 5

Raw material, formulation, or process

Question 6

T or F: Dissolution is the process by which a solid substance dissolves

Answer 6

True

Question 7

Dissolution is controlled by the ______ between the solid substance and the solvent

Answer 7

Affinity

Question 8

Factors that influence the dissolution rate

Answer 8

• Physical characteristics of the dosage form
• Wettability of dosage unit
• Ability of the dissolution medium to penetrate the dosage form
• Swelling process
• Disintegration and deaggregation of dosage form

Question 9

The speed of wetting is dependent on the _______ ______ between the solid surface and dissolution medium

Answer 9

interfacial tension

Question 10

Hydrophobic lubricants such as ____ and ______ ______ slow the penetration rate of the medium; thus slowing the __________ of the granules

Answer 10

talc, magnesium stearate; deaggregation

Question 11

Absorption rate-limiting step for freely-soluble drugs

Answer 11

Diffusion across the GI membrane

Question 12

Absorption rate limiting step for poorly-soluble drugs

Answer 12

Dissolution of the drug

Question 13

Physical parameters that control the rate at which a substance dissolves

Answer 13

• Surface area at a given time
• Shape of the particles
• Nature of the solid/liquid interface
• Solubility of the solid in the dissolution medium

Question 14

Mathematic equation of the rate of dissoltion

Answer 14

dM/dt = KA (Cs - C)
M = mass of the substance dissolved during time t
A = area exposed to the dissolution medium
Cs = solubility of the drug
C = concentration of drug in solution at time t
K = intrinsic dissolution rate constant

Question 15

dM/dt = KACs is known as what equation?

Answer 15

Sink-condition equation

Question 16

The intrinsic rate of dissolution is determined by using either the ____ disk system, or the ____ disk system

Answer 16

rotating; stationary

Question 17

Flux equation

Answer 17

J = (dM/dt) * (1/A)

Question 18

Factors related to the physiochemical properties of the drug (2)

Answer 18

• Solubility

- Particle Size

Question 19

The major factor that determines the rate of dissolution and can be used as a rough predictor of bioavailability

Answer 19

Solubility

Question 20

T or F: Increasing the particle size results into larger surface area, and subsequently faster dissolution

Answer 20

False: Decreasing the particle size increases surface area

Question 21

The surface area accessible by the medium is known as

Answer 21

Effective surface area

Question 22

T or F: It is assumed that the solubility of the drug is dependent on particle size

Answer 22

False: solubility is independent of particle size

Question 23

T or F: Extreme reduction in particle size can lead to an increase in solubility

Answer 23

True

Question 24

T or F: Amorphous form of a drug exhibits greater solubility and faster dissolution rate than the crystalline form

Answer 24

True

Question 25

Factors related to drug product formation (4)

Answer 25

- Effects of diluents - Effects of granulating agents - Effects of disintegrates - Effects of lubricants

Question 26

T or F: The use of hydrophilic diluents such as starch, lactose, microcrystalline cellulose (insoluble) tends to increase the hydrophilicity of poorly soluble active ingredients and result in improvement of dissolution rate

Answer 26

True

Question 27

Which diluent, lactose or calcium carbonate, in warfarin tablets, will result in a greater increase in prothrombin time?

Answer 27

(look up)

Question 28

T or F: Hydrophobic lubricants such as magnesium stearate, aluminum stearate, stearic acid, and talc reduce the wettability of tablets, resulting in longer disintegration time, and smaller area of contact between the active ingredient and dissolution medium

Answer 28

True

Question 29

Factors related to the processes used in the manufacture of the product (2)

Answer 29

- Effect of method of granulation | - Effect of compression force

Question 30

Which granulation method is considered superior with respect to enhancing the dissolution characteristics of tablets

Answer 30

Wet granulation

Question 31

What are five characteristics of compressed tablets that are influenced by the compression force during tableting?

Answer 31

1. Apparent density 2. Porosity 3. Hardness 4. Disintegration time 5. Average primary particle size

Question 32

Factors related to dosage form (2)

Answer 32

- Effect of deaggregation | - Effect of drug-excipient interaction

Question 33

Factors related to the dissolution test

Answer 33

- Agitation intensity - Temperature - Effect of pH - Effect of surface tension - Effect of viscosity

Question 34

T or F: The degree of agitation, or stirring conditions, influences the diffusion-controlled dissolution markedly due to its effect on the diffusion layer

Answer 34

True

Question 35

T or F: Thickness of the diffusion layer is directly proportional to agitation speed

Answer 35

False; it is inversely proportional

Question 36

T or F: Purified water is usually used as the dissolution medium unless investigations show a specific need for an acidic solution

Answer 36

True

Question 37

T or F: Surfactant acting as wetting agents lowers the contact angle and thus improve penetration of the dissolution medium, which leads to an enhancement in dissolution rate

Answer 37

True

Question 38

T or F: The dissolution rate of benzoic acid was found to be inversely proportional to the viscosity of the medium

Answer 38

True

Question 39

USP Method 1 is known as what method of Dissolution?

Answer 39

Rotating basket method

Question 40

USP Method 1 has a stainless steel ____-mesh wire basket that rotates at speeds of ___-___rpm. Temperature is maintained around ___ degrees celsius, and the assembly should not be exposed to significant motion, agitation or vibration. The dosage is placed in the basket at the ____ (start/middle/end) of the test, and is immersed in usually ____mL of dissolution medium

Answer 40

``` 40-mesh 25-150rpm 37 degrees C start of test 900 mL ```

Question 41

USP Method 2 is known as what method of dissolution?

Answer 41

Rotating paddle method

Question 42

In USP Method 2, a _____ is substituted for a basket, and the dosage form is allowed to ____ (float/sink) before the paddle is activated. The apparatus frequently used for both disintegration and nondisintegrating dosage forms at ___rpm.

Answer 42

paddle sink 50rpm

Question 43

For floating dosage forms, a ____ of non-reactive material is used as a "sinker" to keep the unit at the bottom of the vessel.

Answer 43

helix

Question 44

In case of a nondisintegrating dosage form, Apparatus ___(1 or 2) is preferred since the dosage form is kept constrained in steady state fluid flow

Answer 44

Apparatus 1 (basket)

Question 45

USP Method 3 is known as what method of dissolution?

Answer 45

Reciprocating cylinder

Question 46

The assembly of USP Method 3 consists of a set of ____ (metal/glass) reciprocating cylinders fitted with screens on the top and bottom. A ____ and ____ assembly to reciprocate the cylinders ______ (horizontally/vertically) inside their vessels. The GI tract conditions can easily be simulated by making time dependent ___ changes.

Answer 46

Glass motor and drive vertically pH changes

Question 47

USP Method 3 is most suitable for _________ or ______ _____ dosage forms

Answer 47

Nondisintegrating (Extended release) | Delayed-release (enteric coated)

Question 48

USP Method 4 is known as what method of dissolution

Answer 48

Flow-through cell

Question 49

In USP Method 4, a ____ forces the dissolution medium upwards through the flow-through cell at a certain flow rate. The flow profile is sinusoidal with ___ +/- ____ pulses/minute

Answer 49

Pump | 120 +/- 10

Question 50

USP Method 5 is known as what method of dissolution?

Answer 50

Paddle over disk

Question 51

In USP Method 5, apparatus ___ (1, 2, 3, or 4) is used, and a stainless steel disk assembly for holding a ______ _____ is placed at the bottom of the vessel. Temperature is maintained at ____ +/- ___ degrees C

Answer 51

Apparatus 2 Transdermal Patch 32 +/- 0.5 degrees C

Question 52

USP Method 6 is known as what method of dissolution?

Answer 52

Cylinder

Question 53

In USP Method 6, the assembly is the same as apparatus ____ (1, 2, 3, or 4), except the _____ is replaced by a cylinder. The _____ _____ is attached to the cylinder, and temperature is maintained at ____ +/- ____ degrees C

Answer 53

Apparatus 1 Basket Transdermal Patch 32 +/- 0.5 degrees C

Question 54

USP Method 7 is known as what method of dissolution?

Answer 54

Reciprocating disk

Question 55

In USP Method 7, the sample holder is a disk and the system is reciprocated ______ (horizontally/vertically). It is used for _____ ______, and the temperature is maintained at ____ +/- ____ degrees C

Answer 55

Vertically Transdermal patches 32 +/- 0.5 degrees C