Brainscape's Knowledge GenomeTM

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


See full index

GI > Pre-formulation > Flashcards

Pre-formulation Flashcards

1
Q

What is preformulation?

A

Characterising physical and chemical properties of the active pharmaceutical ingredient to produce a stable and bioavailable dosage form that can be mass produced.

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

Optimal aqueous solubility?

A

> 10mg/ml

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

Solubility that requires salt to be made?

A

<1mg/ml

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

Noyes-Whitney equation

A

dm/dt= DA(Ca-C)
————-
H

D= dilution coefficient
A= surface area of drug
H= thickness of boundary layer
Cs= solubility
C= conc. in bulk solvent
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Drug classes for solubility and permeability

A

Class 1: high permeability, high solubility
Class 2: high permeability, low solubility
Class 3: low permeability, high solubility
Class 4: low permeability, low solubility

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

Definition of brick dust

A

Poorly soluble drugs in aqueous solutions

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

Strategies to address low drug solubility

A 
Use of co-solvents (ethanol/water)
Use of salts
Surfactants
Cyclodextrins (sugar/starch compounds that form soluble structures)
Particle size reduction
Lipid based systems similar to micelles
Polymorphs
Co-crystals to form lattice structures
Amorphous solid dispersions
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

High risk compounds

Class 2 or 4

A

Dissolution rate and bioavailability enhanced by non-equilibrium methods or semi-solid/liquid formulations
e.g. amorphous (change of structure), meta-stable polymorphs, solid dispersion, lipid based formulations like soft liquid gelatin capsules

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

Henderson Hasselbalch equation

A

pka= pH + log [HA/A-]

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

More potent and highly specific drugs

A

From lipophilic and water insoluble compounds

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

Salt forms

A

Effect quality, safety and efficacy

Tested separately for toxicity

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

Drugs suited to being salts

A

Drugs with poor solubility that are weak acids or bases

Requires sufficient difference in pka between acid and base (around 3 pka difference)

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

Advantages of salts

A 
Enhanced solubility
Decreased dissolution rate
Easier synthesis and purification
High bioavailability
High melting point
Improved photostability
Better taste
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Disadvantages of salt forms

A 
Lower % of drug
Increased hygroscopicity
More process steps
Increased toxicity
Decreased chemical stability
No change in solubility at various pH’s of GI tract
Increased number of polymorphs
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Formation of drug salt

A

Ionised drug and ionised counterion are liquidised and mixed, ionic interactions form the drug salt in controlled crystallisation

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

Methods of crystallisation

A

Microcrystallisation
Sitting drop method
Hanging drop method

17
Q

Target salts

A 
Consider: 
Structure of substance
Chemical and physical stability
Structurally related compounds
Ease of large scale production
Type of drug
Formulation of final drug
18
Q

Different solid state forms

A

Crystalline (polymorphs, hydrates, solvates)
Chiral
Habits
Amorphous

19
Q

Pharmaceutical parameters that change with crystalline behaviour

A 
Solubility and dissolution rates 
Crystal hardness (compressibility of tablets)
Chemical stability (enthalpy of solution/transition/hygroscopy/melting/sublimination temperatures)
Colour and refractive index
Heat capacity 
Conductivity
Volume
Density
20
Q

What is a habit

A

The external shape of a crystal
Associated with how solute molecules orient themselves when growing
Shape of the crystal is dictated by how each face grows (slowest growing face dominates)
Habit influences flow, compaction, stability and solubility

21
Q

Pharmaceutical effects of habit

A

Injectables: plate like crystals pass through needles better than long thin ones
Tablets: plate like tolbutamol crystals do not flow and have poor compressibility
DPI: needle-like crystals have better fine particle fraction

22
Q

What is crystal structure

A

Composed of periodical aligned building blocks called unit cells which revel the crystal structure and symmetry specific for each substance

23
Q

7 types of cell structure with different lengths and sides

A 
Cube
Tetragonal
Orthorhombic
Trigonal 
Monoclinic
Triclinic
Hexagonal

Triclinic, monoclinic and orthorhombic are common

24
Q

Paracetamol forms

A

Two polymorphic forms:
Monoclinic (more thermodynamically stable at RTP and more commonly used)
Orthorhombic (more easily compressed)

25
Q

What is a crystal form

A

Ordering of atoms and molecules to form a crystal structure (different to outer appearance)
Different crystal forms are polymorphs
Some are pseudopolymorphs like solvates (solvents in crystal lattice) or hydrates (water molecules in crystal lattice)
Chiral molecules can crystallise as mirror images (enantiomorphs)

26
Q

Enantiotrophic

A

Solid phase transition which transforms reversible without passing through liquid or gaseous phas

27
Q

Monotrophic

A

Transition from one polymorph to another (not enantiotrophic) below melting point and is irreversible

28
Q

Regular stacked polymorphs

A 
Lower density
Lower lattice energy
Lower melting point
Faster dissolution rate
Possible fracture lines
29
Q

Interlocking polymorphism

A 
Higher density
Higher lattice energy
Higher melting point
Slower dissolution rate
Lower bioavailability
30
Q

Properties that change with polymorphic form

A 
Melting point
Dissolution rate
Density
Compressibility
Density
Flow ability
Surface properties (surface energy and morphology) 
Habit and crystal structure
Hygroscopicity
Hardness
Stability
31
Q

Organic compounds in preformulation

A

Frequently form hydrates in presence of wafer due to small molecule size of water and multidirectional hydrogen bonding capability of water

32
Q

Hydration number

A

Number of water molecules in a compound

33
Q

Hydrate stability

A

Most stable solid form in water and least soluble form in GI tract
Anhydrous form is usually favoured

34
Q

What is an amorphous solid

A

Where there is no long-range order of positions of molecules/atoms
Have a higher free energy than corresponding crystalline solids and therefore have higher solubility and dissolution rate

35
Q

Formulations of amorphous drugs

A

Solid amorphous dispersions
Lypophilised powders
Oral fast dissolving tablets

36
Q

Solid amorphous dispersions

A

Drug dissolved in polymetric matrix
Molecular dispersion = solid solution
Particulate dispersion = solid suspension
Matrix can crystallise in parts but not completely, major concern if form change or diffusion & crystallisation
Polymer matrix inhibits drug diffusion & cross-linking stabilisers stop crystallisation

GI (21 decks)

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