L15 - Pre-formulation Of Solid Dosage Forms 2

Question 1

What does the functionaly of pharmaceutical products often depend upon? And their performance?

Answer 1

• the physical form of the drug
• understanding the physical properties

Question 2

What is the single biggest factor affecting the performance, development, patentability, manufacturing and profitability of a compound?

Answer 2

The physical form of a drug (solid state)

Question 3

What are the different solid-state forms?

Answer 3

• crystalline (polymorphs, hydrates, solvates)
• chiral
• habits
• amorphous

Question 4

What are examples of amorphous and crystalline compounds?

Answer 4

• instant coffee, hailstones
• filter coffee, snow crystals

Question 5

What can change with crystalline behaviours?

Answer 5

Highly important pharmaceutical parameters

Question 6

What properties are determined primarily by the nature of the crystal structure?

Answer 6

• solubility and dissolution rates
• crystal hardness (compressibility)
• chemical stability ( enthalpy of solution, transition, hygroscopicity, melting, sumblimation temp)
• colours, refractive index, heat capacity, conductivity, vol, density

Question 7

What is the crystal habit?

Answer 7

The external shape of a crystal

Question 8

What is the crystal habit associated with?

Answer 8

The way solute molecules orientate themselves when growing

Question 9

What is the general shape of a crystal related to?

Answer 9

The growth of individual crystal faces

Question 10

What face dominates?

Answer 10

The slowest growing one

Question 11

What does crystal habit influence?

Answer 11

• flow
• compaction
• stability
• solubility

Question 12

What are the miller indices?

Answer 12

The designated index plane that each crystal face has

Question 13

What does the miller index provide information about?

Answer 13

The molecular ordering of the surface of a crystal face

Question 14

What are injectables?

Answer 14

Plate like crystal pass through needles better than long needle like crystals

Question 15

What is tableting?

Answer 15

Plate like tolbutamol crystals do not flow and have poor compressibility

Question 16

What does needle-shaped paracetamol crystal powder show?

Answer 16

Poorest compression properties
- shows greater capping and lamination than the plate or cube shaped crystals

Question 17

What are dry powder inhaler (DPI) formulations?

Answer 17

Needle like crystals usually have better fine particle fraction

Question 18

What unit cells?

Answer 18

The periodical aligned building blocks a crystal is composed of

Question 19

What do unit cells reveal?

Answer 19

The crystal structure and symmetry specific for each substance

Question 20

How many types od crystal structures are there and what are they defined by?

Answer 20

7
- lengths and angles between each side of the unit cell

Question 21

What are the 7 primitive unit cells?

Answer 21

• cubic
• tetragonal
• orthorhombic
• trigonal
• monclinic
• triclinic
• hexagonal

Question 22

What do drug molecules typically form?

Answer 22

Triclinic, monoclinic and orthorhombic unit cells

Question 23

What are bravais lattices?

Answer 23

The 14 different configurations that molecules can arrange themselves into

Question 24

What 2 polymorphic forms does paracetamol exist in?

Answer 24

• monoclinic (form 1)
• orthorhombic (form 2)

Question 25

Why is form 1 commercially used? But what is it not suitable for?

Answer 25

• more thermodynamically stable at room temp
• direct compression, has to be mixed with binding agents before tableting

Question 26

What is crystal form?

Answer 26

The ordering of atoms and molecules to form crystal structure
- doesn’t mean outer appearance (habit) of the crystals/particles

Question 27

What is polymorphism?

Answer 27

When the same chemical compound exists in different crystal forms

Question 28

What are polymorphs in special cases?

Answer 28

Pseudopolymorphs
- solvates (solvent molecules in crystal lattice)
- hydrates (water molecules in crystal lattice)

Question 29

What is enantiomorphism?

Answer 29

When the chiral molecules can crystalise as mirror images of each other

Question 30

What are racemic mixture?

Answer 30

A mixture of D (dextro) and L (levo) crystal forms

Question 31

What does the tern enantiotropic mean?

Answer 31

When a solid phase transition which transform reversibly without passing through the liquid or gaseous phases

Question 32

What does the term monotropic mean?

Answer 32

When the solid phase is not able to transition reversible before a phase change

Question 33

What happens when a transition from one polymorph to another happens below melting point?

Answer 33

Then it is irreversible

Question 34

What properties does form II have?

Answer 34

• lower density
• lower lattice energy
• lower mp
• faster dissolution rate
• possible fracture line

Question 35

What properties does form I have?

Answer 35

• higher density
• higher lattice energy
• higher mp
• slower dissolution rate
• lower bioavailability

Question 36

What properties may change with polymorphic form? (10)

Answer 36

• mp
• dissolution rate
• compressibility
• density
• flowability
• surface properties (surface energy and morphology)
• habit and crystal shape
• hygroscopicity
• hardness
• stability

Question 37

Why is polymorphism essential during preformulation stage?

Answer 37

Important that the most thermodynamically stable polymorph is formed
- more favourable form may be obtained upon scailing up

Question 38

What can occur during processing and storage?

Answer 38

Moisture mediated and solid state phase transformation from one polymorp to another

Question 39

What is CAPP?

Answer 39

Chloramphenicol-3-palmitate
- broas spectrum antibiotic

Question 40

How many forms can CAPP crystallise into? And which is most thermodynamically stable?

Answer 40

3 polymorphic forms
- form A is most stable
- but form B has eightfold higher bioactivity than A

Question 41

What can CAPP create?

Answer 41

The danger of fatal dosages
- unwanted polymorph is unwittingly administered because of alterations in process or storage conditions