Block 4 -- Drug Product Development

Question 1

What are the 3 steps in manufacturing?

Answer 1

1) preformulation
2) formulation
3) manufacturing

Question 2

What classification in the BPC are most pharmaceuticals?

Answer 2

BPC 2 & 4 (solubility-limited)

Question 3

What are types of crystalline defects?

Answer 3

1) interstitial atom
2) substitutional atom
3) vacancy
4) frenkel pair

Question 4

What is “alpha” in the Prout-Tompkins equation?

Answer 4

alpha = the fractional extent of the reaction

Question 5

What are the types of degradation reactions?

Answer 5

1) Hydrolysis
2) Oxidation
3) Photolysis
4) Dehydration

Question 6

What is the IPEC definition for an excipient?

Answer 6

Compounds other than API that have been evaluated for safety, and have any of the following roles:

1) aid in processing
2) aid in stability, F, patient acceptability
3) aid in Product ID
4) contribute any other attribute for safety/efficacy

Question 7

What is the IPEC?

Answer 7

International Pharmaceutical Excipients Council

Question 8

How are most excipients currently obtained?

Answer 8

Synthesis

Physical modifications of natural compounds

Question 9

What is the purpose of diluents?

Answer 9

bulking agents

• • practical weight
• • compression aid
• • improve powder flow

Question 10

What are examples of diluents?

Answer 10

1) Microcrystalline cellulose
2) Lactose
3) Calcium phosphate dibasic dihydrate
4) Starch
5) Compressible sugar

Question 11

What is the Mallard reaction?

Answer 11

Reducing sugar (lactose) reduces API

Question 12

What is the purpose of disintegrants?

Answer 12

break up drug product to enhance dissolution

Question 13

What are examples of disintegrants?

Answer 13

1) Sodium starch glycolate
2) Croscarmellose sodium
3) Crospovidone
4) Starch

Question 14

What are the purposes of binders?

Answer 14

• • mechanical strength

- - creation of granules in wet milling

Question 15

What are examples of binders?

Answer 15

1) Polyvinylpyrrolidone (PVP)
2) Starch
3) Microcrystalline cellulose
4) Polymers

Question 16

What purposes do lubricants serve?

Answer 16

1) prevents adherence to die

Question 17

What are examples of lubricants?

Answer 17

1) Mg Stearate
2) Stearic acid
3) Lubritab (hydrogenated vegetable oil)
4) Talc

Question 18

How are lubricants used in manufacturing?

Answer 18

• • added right before addition to dye

- - levels normally 0.5 - 2%

Question 19

What is the purpose of a glidant?

Answer 19

1) improved flow

2) reduce inter-particle friction

Question 20

What are examples of glidants?

Answer 20

1) fumed silica

2) talc

Question 21

How are glidants used in manufacturing, and what are some concerns?

Answer 21

• • normal levels <0.2%, very fluffy

- - can have asbestos contamination

Question 22

What agents are used for controlled release?

Answer 22

1) hydroxypropylmethylcellulose (HPMC)

2) Xanthan gum

Question 23

What are examples of protectants?

Answer 23

Eudragits– Polymethylacrylates

Question 24

Describe the points in manufacturing where excipients are added.

Answer 24

All are during final mixing with these exceptions:

1) filler during initial mixing
2) binder during wet granulation

Question 25

What are the criteria for tablet manufacture?

Answer 25

1) dose uniformity
2) disintegration, dissolution
3) uniform coating
4) mechanical strength
6) stable, soluble, easy to administer

Question 26

List the unit operations:

Answer 26

1) Weighing
2) Blending/Mixing
3) Milling
4) Granulation
5) Drying
6) Compaction
7) Coating
8) Packaging

Question 27

What machines are used for blending?

Answer 27

y,cone, rotating cube, double cone, oblique cone, v mixer, turbula, bowl mixer, slant cone

Question 28

What methods are used in milling?

Answer 28

cutting
compression
impact
attrition

Question 29

What machines are used in milling?

Answer 29

Fitz Mill

CoMill

Question 30

What are the purposes for granulation?

Answer 30

1) better mixing
2) improved flow
3) avoid toxic dust
4) lessen impact of moisture

Question 31

What machines are used in wet granulation?

Answer 31

1) high speed mixer

2) fluidized-bed granulator

Question 32

What are the methods used in dry granulation?

Answer 32

slugging

roller compaction

Question 33

How is size selected in dry granulation?

Answer 33

Selective screen size

Question 34

What are the steps in tablet formation?

Answer 34

1) dye filling
2) tablet formation
3) ejection

Question 35

What machines are used in tablet manufacture? Describe their qualities.

Answer 35

1) Tablet Presses
- - single punch, 200/min
2) Rotary Presses
- - multi-punch, 10k/min

Question 36

What tests are used after tablets are manufactured?

Answer 36

thickness, hardness