Drug Product Development

Question 1

What is preformulation?

Answer 1

Determining the physicochemical properties necessary to formulate the compound

Question 2

What is formulation?

Answer 2

Determining the route and composition of the final dosage form

Question 3

What is manufacturing?

Answer 3

The unit operations that are necessary for final dosage preparation

Question 4

What are the two things to be concerned about for preformulation?

Answer 4

Solubility

Stability

Question 5

What is solubility?

Answer 5

Equilibrium State

Some leave the surface, some attach to surface and a products solubility is reaching the equilibrium between these.

Question 6

What is solubility usually described as?

Answer 6

Maximum amount of solute that can be dissolved per 100g of water. it could also be moles of solute per liter of solution.

Question 7

How are organics solubility?

Answer 7

Low solubility, unless they are salts

Question 8

What are the 3 states of solubility?

Answer 8

Completely soluble
Supersaturated
Very supersaturated (labile)

Question 9

Which of the 3 states of solubility results in crystallization?

Answer 9

supersaturation

Question 10

What are 2 properties of stability?

Answer 10

Physical and Chemical

Question 11

How does physical stability work?

Answer 11

When it transforms to different crystal forms, but the chemical stays in tact. Eg. crystalline to amorphous, hydrates, solvates

Question 12

What defines chemical stability?

Answer 12

Chemical reactions.

Results in degradation of product that must be characterized

Question 13

Why are solids very stable?

Answer 13

The crystal lattice helps to keep molecules from reacting

Question 14

Is the crystalline form or amorphous form more reactive?

Answer 14

Amorphous

Question 15

Where do reactions start?

Answer 15

At crystal defects

Question 16

What are the 5 crystal defects?

Answer 16

Interstitial atom
Substitution larger atom
Substitution smaller atom
Vacancy
Frenkel-pair

Question 17

What does the Prout-Tompkins equation describe?

Answer 17

Reactivity in solids

Question 18

Are you more concerned with an initial degradation or later degradation in a product?

Answer 18

Initial because later degradation means it was a failed product.

Question 19

What are 4 reactions that can ruin the stability of your drug?

Answer 19

Hydrolysis
Oxidation
Photolysis
Dehydration

Question 20

What is the IPEC?

Answer 20

International Pharmaceutical Excipients Council

Question 21

What is the IPEC definition of an excipient?

Answer 21

Any substance other than the active drug or prodrug which has been appropriately evaluated for safety and is included in a drug delivery system for a specific purpose

Question 22

What does the USP do?

Answer 22

Provides test procedures and specifications to find the right excipient

Question 23

What are the 6 types of excipients?

Answer 23

Diluents
Disintegrants
Binders
Lubricants
Glidants
Controlled release

Question 24

What is a diluent?

Answer 24

Bulk forming agent
Helps make weight practical for tablet
Helps keep tablet together
Enhances powder flow for manufacturing

Question 25

What are some examples of diluents?

Answer 25

``` Microcrystalline cellulose Lactose Calcium phosphate dibasic dihydrate Starch Compressible sugar ```

Question 26

What is a disintegrant?

Answer 26

Breaks up solid dosage form, enhancing dissolution | Works by either water uptake and/or swelling

Question 27

What are some examples of disintegrants?

Answer 27

Sodium starch glycolate Croscarmellose sodium Crospovidone Starch

Question 28

What is a binder?

Answer 28

Gives tables mechanical strength, creates granules in wet milling Works by either water uptake and/or swelling

Question 29

What are some examples of a binder?

Answer 29

Polyvinylpyrrolidone (PVP) Starch Microcrystalline cellulose Polymers

Question 30

What are lubricants?

Answer 30

Prevents adherence of tablet to the die after compaction Over lubrication can affect the dissolution Used at levels of 0.5%-2%

Question 31

What are some examples of lubricants?

Answer 31

Magnesium stearate Stearic acid Lubritab Talc

Question 32

What are glidants?

Answer 32

``` Improves powder flow Stops inter-particle friction Used at levels <0.2% Low bulk density Can have problems with asbestos (with talc) ```

Question 33

What are some examples of glidants?

Answer 33

Fumed silica | Talc

Question 34

What are controlled release/protection?

Answer 34

Used to extend the release of drug from a matrix

Question 35

What are some examples of controlled release?

Answer 35

HPMC | Xanthan gum

Question 36

What are some examples of protection?

Answer 36

Eudragits | Won't dissolve until it reaches a high pH

Question 37

Where does manufacturing start?

Answer 37

Preformulation

Question 38

What are two ways to adjust particle sizes and how do they effect the particle?

Answer 38

Milling-decreases | Granulation-increases

Question 39

Why do we adjust the particle size?

Answer 39

If the particles are different sizes they will not properly mix

Question 40

What are 4 ways to mill?

Answer 40

Cutting Compreshion Impact Attrition

Question 41

What is the definition of milling?

Answer 41

Create a stress on particle to cause it to break

Question 42

What are two examples of milling machines?

Answer 42

Fitz Mill | CoMill

Question 43

What are two methods of granulation?

Answer 43

Wet granulation | Dry granulation

Question 44

What are the two processes of wet granulation?

Answer 44

Nucleation | Ball growth

Question 45

What are 4 types of granulation?

Answer 45

Coalescence Breakage Abrasion transfer Layering

Question 46

What are two machines used for wet granulation?

Answer 46

High speed mixer/granulator | Fluidized-bed granulator

Question 47

What are two methods of dry granulation?

Answer 47

Slugging-not as much | Roller compaction

Question 48

What is the name of a machine for roller compaction

Answer 48

Roller compactor

Question 49

What press is used for small manufacturing?

Answer 49

Tablet press

Question 50

What press is used for large manufacturing?

Answer 50

Rotary press

Question 51

What tests are ran after the tablet has been made?

Answer 51

Tablet thickness Hardness test