Brainscape's Knowledge GenomeTM

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


See full index

Pharmaceutics > 4 Preformulation > Flashcards

4 Preformulation Flashcards

1
Q

What is preformulation?

A

Gathering information regarding properties which may have a bearing on product formulations.
Problems are identified and ways around it can be established.

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

What is the object of dosage form development?

A

To develop a stable, bioavailable product with good acceptance.

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

What must the formulator develop?

A

A specific detailed formulation procedure and define specification of raw , excipients and finished product.

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

What are organoleptic properties?

A

The description of drug substance, including colour, odor and taste.

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

How do we remedy objectionable color?

A

By use of a colouring agents or coating the tablet

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

How can we remedy objectionable odors?

A

A coating or the inclusion of an aromatic excipient

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

How can we remedy objectionable taste?

A

By use of a flavouring agent, a coating or use of an insoluble salt form

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

What are the 5 tastes recognized?

A

Bitter, sour, sweet, salty and umami

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

What are the groups associated with each taste?

A 
Bitter: Amine groups (alkaloid quinine)
Sour: Acids (citric acid)
Sweet: Hydroxyl groups (glycerol, sugars)
Salty: Inorganic salts (NaCl, KCl)
Umami: Some amino acids (glutamate)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What should you know about the purity? Why?

A

Must know and define the level of material purity and what impurities it may present
Trace amounts of metal can affect stability, impurities may be toxic.
May require addition of excipients or limit test development.

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

What are micromeretics?

A

The particle size, shape and surface area of drug material. Plays role in homogeneity of tablet.
Small particle size increases surface area which will be in contact with excipient, oxygen and moisture.

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

What problems arise from milling?

A

Static electricity, agglomeration and polymorph formation.

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

Why is solubility important?

A

The product must dissolve in gastrointestinal fluids prior to absorption.
Usually better dissolution means better bioavailability.
Solubility >1% does not present dissolution/bioavailabilty problems.

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

What relationships must we know to solubility?

A

The relationship between medium pH, solubility and stability.

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

How do we determine potentially useful salts?

A

For HCl salts of oral products you must assess the common ion effect.
Determine the pKa of drug if ionizable.

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

What do you do if the drug is not ionizable?

A

May include the use of a metastable polymorph, use of complexes, solid solution techniques, incorporation of surfactants and particle size reduction (micronization).

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

Why would we want reduced solubility?

A

For stability and organoleptic reasons.

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

What if kd is slower than ka?

A

Then absorption is limited by dissolution rate.

Any change in kd will affect absorption rate.

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

What is ka?

A

Rate of permeation across membranes.

Can be rate limiting step.

20
Q

What are the 2 steps required for absorption of drugs as oral solids?

A

Dissolution and transport of dissolved material across the GI membranes into the blood stream.

21
Q

How can we assess the partition coefficient (P)?

A

In water/octanol or water/chloroform. Usually expressed as log P.
P=[organic]/[aqueous]
Larger value, more affinity for organic phase.
log P= 1 means 10 organic:1 aqueous

22
Q

How does pKa affect where a drug is absorbed?

A

Weak acids are absorbed better in the stomach. Basic drugs are better absorbed in the intestine.

23
Q

How can we study absorption?

A

Using the everted gut technique or Franz cells.

24
Q

How may solid drug materials occur?

A

As crystalline substances with an identifiable definite shape or as amorphous particles without definite structure.

25
Q

What is the difference between amorphous and crystalline states?

A

Amorphous forms are more soluble and show better availability.
Crystalline form is more stable.
Chloraphenicol palmitate crystalline form is abosorbed in GI, amorphous is not.
Amitriptyline and penicillin are absorbed in both forms

26
Q

What must we ensure during processing with a drug capable of forming polymorphs?

A

Must ensure that processing does not cause a transition.

Can happen after milling, granulation, drying or compression.

27
Q

What may granulation or drying cause?

A

Granulation: Polymorph transformation, formation of solvates or hydrates.
Drying: Polymorph transformation, transformation to anhydrous crystalline or amorphous forms.

28
Q

What will affect the flow and compression in tableting?

A

Morphology, tensile strength and density of powders.

29
Q

What do stability studies for tablet dose form include?

A

Solid state stability of drug alone, stability in the presence of potential excipients and stability of drug in solution (granulation).

30
Q

What properties influence stability?

A

pKa, solubility, melting point, crystal habit and form and equilibrium moisture content.

31
Q

What mechanisms are more difficult to evaluate?

A

Mechanisms in solid state degradation.

32
Q

What are the most common factors for instability?

A

Light, heat, oxygen and moisture.

Interplay among factors

33
Q

How is data from stability screening analyzed?

A

Using multiple linear regression (MLR) and fit to a general equation.

34
Q

How are solid state reactions done?

A

They are slow, so stress conditions are used and extrapolated down to storage conditions (use caution)
Temps 40-70 compared to 5 degree cold
If no change at 60 after 30 days, stability is good

35
Q

What happens to drugs in the presence of moisture?

A

Drugs may hydrolyze, react with excipients or oxidize.

36
Q

How is humidity stability tested?

A

Increasing humidity levels under constant temperature.

Humidity levels achieved using saturated solutions of various salts.

37
Q

How does humidity stability data help?

A

Helps decide if the product should be protected from moisture in a low humidity environment, aqueous based granulation systems or whether we should be careful of excipients which absorb atmospheric moisture.

38
Q

What excipients do tablets usually contain?

A

Binders, disintegrants, lubricants and fillers.

Sometimes reaction between drug and excipient (lactose and haloperidol)

39
Q

How are pull samples examined?

A

By TLC, HPLC or differential thermal analysis (DTA).

40
Q

How is photosensitivity estimated?

A

By exposing the drug substance to 400 and 900 foot-candles of illumination for 2-4 weeks.

41
Q

How is stability to oxygen examined?

A

Samples are held in an atmosphere of high oxygen tension (40%) and compared to a sample stored in inert atmosphere.

42
Q

Why should we be concerned about density?

A

It provides a rough idea of the size of the finished product.
Affects flow properties, if excipients of different density are used, blending may a problem due to segregation.

43
Q

How can we protect from oxidation?

A

Remove oxygen by putting N2 in headspace
Buffer to acidic pH
Include an antioxidant like bisulfite or ascorbic acid
Chelate metal ions using EDTA

44
Q

How can flow properties affect the drug?

A

Good flow is essential for blending, granulation and compression.
Angle of repose is used to assess. 25-45 degrees is preferred.

45
Q

What is the ideal compressibility of a drug?

A

We want a powder that forms a hard uniform compact under moderate pressure.
Capping or chipping should not occur.

Pharmaceutics (4 decks)

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