Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

Ph@rm@ > Module 6 > Flashcards

Module 6 Flashcards

(73 cards)

Start Studying
1
Q

Drug = Active +

A

Excipient

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

therapeutic ingredient

A

Active (API)

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

____ of the API is critical!

A

Purity and form

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

______ as a tool

A

Crystallization

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

Complexities of crystallization

A

Polymorphism, solvent selection,
existence of the metastable and spinodal state, etc.

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

Mechanisms of crystallization: physical landscape of
crystallization

A

Kinetic driver for nucleation
and growth?

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Mechanisms of crystallization: energy landscape of crystallization

A

Thermodynamic driver for
nucleation and growth?

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

Relative rates to grow macroscopic crystals

A

Nucleation kinetics

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

Relative rates to grow crystals to a specific morphology

A

Crystal growth kinetics

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Impurities affecting crystallization rates

A

Secondary nucleation
Occlusion
Inclusion
Attachment to surfaces

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

__________ is inherently random, poorly understood, difficult to study, thus very difficult to control

_________ is “reasonably” more understood

________ are two-edged swords

A

Nucleation; crystal growth; impurities

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

________ is the process of adding
homogeneous or heterogeneous crystals as a catalyst to a crystallizing solution to nucleate and/or grow more crystals.

A

Crystal seeding

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

A seed crystal… (4)

A

provides a starting point for nucleation and growth.

can be used to create a specific crystal structure.

can be used to grow larger, more uniform crystals.

can be used to grow crystals in a controlled manner.

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

_______ is the first and essential step for control of a
crystallization process.

A

Seeding

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

The seed will immediately dissolve
since the mixture is not saturated
at this region.

A

(Unsaturated) solution

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Spontaneous crystallization would
have already occurred at this point.

A

Suspension

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

The proper region to add a seed,
since nucleation is still on-going

A

Metastable zone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

A key consideration is the
width of the Metastable Zone. The Mzwidth of KNO3 is ____, AZ5 is ____, AZ6 is _____, AZ7 is _____, and AZ8 is _____.

A

2, 8, 19, 39, >50

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Errors and inaccurate
temperature readings during
solubility studies can cause
________ in a
crystallization process.

A

loss of control

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

If the system is polymorphic, and stable polymorph is desired, seeding between the ________ minimizes the risk of generating the metastable polymorph.

A

two solubility curves

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

T/F: Seeding alone does NOT guarantee control of crystal form and size.

A

True

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Possible outcomes of seeding (3)

A
  1. There could be a mixture of crystal structures.
  2. The desired crystal structure i s obtained but particle size is not controlled.
  3. The structure and size is controlled.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

The most important factor controlling the rate of crystallization is the thermodynamic
driving force – the ________.

A

supersaturation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

For supersaturation, applying a linear cooling rate results to __________ and _________.

A

Build up of supersaturation
at the start; nucleation
dominating over crystal growth

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
For supersaturation, applying a non-linear cooling rate results to __________ and _________.
Slow cooling at the start allows S to be constant; Growth dominates over nucleation
26
Knowing how impurities _______ is a critical step for the selection of adequate control strategies that are directed to the root cause of ________.
incorporate in the growing solute; impurity incorporation
27
Diagnosis of impurity incorporation
- Process imaging - Dry powder analysis - Powder dissolution - Impurity adsorption tests - Single - crystal analysis
28
Diagnosis technique that uses in - situ imaging probes integrated to crystallization systems. Non -invasive; provides valuable information not possible thru offline tests.
Process imaging
29
Diagnosis of analysis of powders by X-ray powder diffraction (XRPD) can reveal information on crystallizing impurities, seen as the appearance of a new pattern revealing a mixture of crystalline phases or formation of a co- crystal.
Dry powder analysis
30
Diagnosis where hypothesized impurity distribution maps based on progressive powder dissolution tests.
Powder dissolution
31
High degree of dissolution in the early steps is assumed to indicate that the impurities are located at the surface.
Zone A (Surface)
32
Impurities dissolving towards the later steps indicate that they are predominantly inside the crystal.
Zone B (Inclusion and substitution)
33
Diagnosis where they use of different particle sizes for the diagnosis of surface impurities.
Impurity adsorption tests – powder-based
34
For Impurity adsorption tests – powder-based, if the impurities are located at the surface, ______ crystals with a _______ surface area per unit volume will present a ______ purity.
smaller; higher; lower
35
Warnings for Impurity adsorption tests – powder-based
Make sure that impurities did not co-precipitate during crystallization. Lower purities for larger crystals could be a consequence of a spread in nucleation times, solution entrapment, or agglomeration.
36
This analysis is used to: i . diagnose the location of impurities within a crystal, ii. provide the highest level of fundamental understanding of the relationship between surface chemistry, crystal growth, and impurity incorporation.
Single - crystal analysis
37
Strategies for impurity prevention and control
✓ Solvent selection for crystallization and washing ✓ Predictive models ( e.g., population balance, nucleation and growth kinetics ) ✓ Impurity complexation ✓ Slurry aging and temperature cycling
38
_______ is driven by the generation of a supersaturated state for those impurities.
Impurity precipitation
39
If impurity concentration is too high, or the solubility in the crystallization solvent is too low – impurities may _________ with the product of interest.
precipitate together
40
Co -formers that can form a co-crystal with the impurities will also form a _______ in solution.
complex
41
_________ prevents impurities from incorporating in the growing crystals.
Complexation
42
In cases where prevention of impurity incorporation is not trivial or practical, an alternative to improve the purity of the final product is to implement strategies to selectively dissolve impurities post- crystallization by __________
Slurry aging and temperature cycling
43
________selectively dissolve impurities post - crystallization
Slurry aging and temperature cycling
44
Strategies for slurry aging
§ Suspension of impure crystals in a wash solvent. § Application of mechanical agitation to promote crystal breakage and expose the impure crystal core to the wash solvent. § Preferential dissolution of the impure core.
45
Strategies for temperature cycling
§ A method to accelerate the purge of impurities in equilibrium suspensions. § The dissolution of impure crystals and re-crystallization at low supersaturations is promoted by heating and cooling cycles, triggering small increases and drops in solubility for both the solute and the impurities.
46
Application of ______ to promote crystal breakage and expose the impure crystal core to the wash solvent.
mechanical agitation
47
The ______ of impure crystals and _________ at low supersaturations is promoted by ______ cycles, triggering small increases and drops in solubility for both the solute and the impurities.
dissolution; re-crystallization; heating and cooling
48
_________ was synthesized in the presence of sodium alginate (SA).
Struvite
49
Struvite crystal habit changed from ________ to ________ morphology, at increasing SA concentrations.
prismatic; plate-like twinned
50
Crystallization of API in pure system
End of crystallization in <1 hour
51
Crystallization of API in the presence of an additive.
Lower yield, change in crystal habit
52
Additive-mediated glycine crystallization in _______ environments
quiescent
53
Inorganic salts can drive _________ for glycine.
selective polymorphism
54
__________ salts inhibited crystallization of glycine. Taking _ days for crystals to appear.
Divalent; 7
55
Needle-like crystals are characteristic of ____-glycine
gamma
56
Crystals formed after 7 days were identified as _____-glycine.
alpha
57
Impurities may or may not provide control to a crystallization process.
Control Of Crystallization.
58
Impurities may increase rates (i.e., _________) or decrease rates (i.e., inhibitors, _______).
secondary nucleation; complexation
59
Surface - active impurities may __________ on crystal faces – directing growth to a different _________.
preferentially adsorb; crystal habit
60
T/F: Thermodynamics do not change with scale. Kinetics are also independent of scale. Problems with scale-up of crystallization processes still occur.
True
61
________ is impacted with temperature control issues during scale -up.
Cooling crystallization
62
_________ and/or seeding and the use of additive may cause _________ supersaturations in the reactor mainly due to mixing __________.
Antisolvent addition; inhomogeneous; sensitivities
63
The _________ nature of a crystallization set-up introduces additional sensitivities to mixing.
multiphase
64
API - solvent density differences may cause ________ of API crystals which impacts mixing.
sinking
65
Vessel design considerations (i.e., baffles, agitators, vessel shape, etc.) to ensure good suspension and minimize other phenomena like ________.
attrition
66
Enabling technologies in the laboratory scale:
- Turbidity for nucleation and dissolution - Chord length for seed and particle fingerprinting - In-process cameras for morphology - NIR and Raman for polymorph screening - ATR- FTIR and ATR UV-Vis for solution concentration.
67
Seeding behavior changes with scale - in -line monitoring of _________ may be helpful.
chord length
68
Use of __________ – is it useful considering our understanding of supersaturation?
feedback control
69
In-line monitoring of _________ – is this possible?
crystal purity
70
One should know what they are trying to make. Multiple experiments need to be done just to determine the desired crystal form. Yield and productivity are not even relevant.
Make the first seed.
71
With a good choice of solvent and a proper way to generate supersaturation, API crystallization can be designed to be fast, high yielding, and productive while maintaining robustness.
Produce that desired crystal.
72
________ go hand -in- hand in ensuring a controlled crystallization process. _______ the crystallization process (whether it be cooling crystallization or antisolvent crystallization) is an important step in crystallization.
Kinetics and thermodynamics; Monitoring
73
The _______ crystallization of an API should be performed as the _____ step of the formulation process.
final; first

Ph@rm@ (11 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions