Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

PY366 Drug discovery > Preformulation procedures for new drugs > Flashcards

Preformulation procedures for new drugs Flashcards

(74 cards)

Start Studying
1
Q

what are the events in product development

A
  1. synthesis/isolation
  2. biological activity
  3. preformulation
  4. formulation development
  5. pre clinical and clinical testing
  6. IND/NDA application
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

what is the aim of a formulation scientist

A

to develop a pharmaceutical product for a drug suitable for administration to humans

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

what are the criteria for development

A
  • effective
  • ideal administration
  • stable
  • ideal for large scale manufacturing
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

what is preformulation

A

the first stage of formulation development process
- a collation of steps that are performed before actual formulation development is started
- logical sequence of events
- must be performed for all types of dosage forms

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

what are the pre-requisites for pre formulation

A
  1. synthesis- a small amount of the drug has been synthesised with suitable purity
  2. pharmacology- the drug has demonstrated the desired pharmacological effect in animal models or cell culture models
  3. toxicology- toxicity of the drug has been determined
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

what is the 1st step in preformulation

A

development of analytical techniques
- to determine identity
- to assay the drug

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

what can be used for identifying the drug substance

A

spectroscopy
- NMR
-MS
-UV/VIS
-IR
also give us the purity of the drug molecules and identification of any potential contaminants

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

why do we need accurate analytical data

A

to accurately determine the concentration of the drug in the dosage form and in biological samples

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

what methods are available to determine the concentration of a substance in a matrix formulation, biological sample or extraction sample

A
  1. traditional methods- TLC, UV/VIS, simple HPLC
  2. modern methods- HPLC-MS, UPLC-MS
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What properties should an analytical method have for validation

A
  • sensitive
  • selective
  • reproducible
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

how do you validate an analytical method

A
  1. basic information
    - MW
    - purity
    - chemical structure
    - any info on synthetic impurities or degradation products
  2. physicochemical parameters
    - solubility
    - pKa
    - partition coefficient
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

how is data interpreted following method validation

A
  1. prepare a calibration plot or linear response graph for the drug
  2. extract the drug from the formulation into a solvent
  3. analyse the sample using the method
  4. calculate the concentration in the sample
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

give examples of physicochemical properties of a drug

A
  • particle size
  • crystal properties
  • solubility
  • pKa
  • log P
  • dissolution
  • organoleptic properties
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

what does particle size directly influence

A
  1. solubility and dissolution rate
  2. content uniformity in the final dosage form
  3. flow characteristics
  4. sedimentation rate
  5. bioavailability
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

what is the recommend particle size for inhalation

A

<5um in diameter
- eg corticosteroids and bronchodilators

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

what is the recommended particle size for suspensions

A

> 1um in diameter
- should have some degree of wettability

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

what can be the problems with crystal properties

A
  • uneven crystal shapes
  • difficult to formulate as crystal shape affects flow properties
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

what can be used to obtain uniform crystal shapes

A
  • crushing
  • spray drying
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

how do crystal properties affect melting point

A

require only a small amount of material to get information regarding stability and solubility

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

what can be used to measure crystals

A
  1. capillary melting point apparatus
  2. hot stage microscopy
  3. differential scanning calorimetry or thermal analysis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

what is a polymorphism

A

where a solid material exists with at least 2 different molecular arrangements which give distinct crystal species

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

what are the types of crystals

A
  1. polymorphs
  2. solvates- contain trace amounts of solvent used for crystallising the drug
  3. hydrates- water bound to drug molecules
  4. amorphous
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

what can differential scanning calorimetry be used to identify

A
  1. how many polymorphs of the drug exists
  2. how stable each form is
  3. is there a glass transition state
  4. can the metastable form be stabilised
  5. how will processing and storage affect stability of the polymorph
  6. what is the solubility of each polymorph
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

what is meant by solubility

A

the maximum amount of drug that can be dissolved in a selected solvent at equilibrium conditions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
what are the 2 types of solvents
1. aqueous solvents- water, buffer solutions 2. non aqueous solvents- oils, waxes
26
what measure of aqueous solubility represents good bioabsorption
aqueous solubility >10mg/ml
27
what temperature is intrinsic solubility measured at
measured at 4 degrees and 37 degrees
28
what are the 2 types of pH of solubilised drug
acidic or basic
29
what is a weak base
soluble in acidic solution but not in water
30
what is a weak acid
soluble in alkaline solution but not in water
31
what does an aqueous solubility of free acid/base <1mg/ml indicate
indicates the need for a salt
32
what are the factors involved in salt selection
1. hygroscopic nature 2. solubility and bioavailability 3. physical and chemical stability - polymorphisms - incompatibilities - degradation 4. each salt form is a different NCE
33
what is the Henderson-hasselbach equation for weak acids
pH= pKa + log10[A-]/[HA]
34
what is the Henderson-hasselbach equation for weak bases
pH= pKa + log10[B]/[BH+]
35
what is the partition coefficient
- solvent:water quotient for drug distribution - measure of relative lipophilicity (logP) of a drug between octane and water - indicates membrane penetration ability and absorption
36
how is the partition coefficient determined
by shake flask method
37
what is dissolution
a dynamic process by which a material is dissolved in a solvent and the rate is characterised - amount of drug dissolved over a given time
38
describe the dissolution rate in a weakly basic drug
will have a high dissolution rate and high solubility in stomach but not lower down the GIT
39
describe the dissolution rate in a weakly acidic drug
has a lower dissolution rate and is less soluble in the stomach and more soluble down the GIT
40
how is intrinsic dissolution rate of a compound reduced
due to common ion effect
41
give examples of organoleptic modifiers for oral drug delivery
1. natural sources - sweeteners (sorbitol) - fruit extracts (citrus) - natural colouring agents (b carotene) 2. synthetic sources - artificial fruit flavours - colouring agents
42
what potency is recommended at storage conditions
potency >95% at recommended storage conditions
43
what are forced drug stability tests performed at preformulation
determines 1. stability of the drug in extreme conditions 2. identifies breakdown products 3. excipient incompatabilities 4. storage conditions 5. package conditions and incompatibilities
44
what are the different types of drug degradation
1. hydrolysis due to acid or base 2. oxidation/reduction due to metal ions 3. photolysis due to UV or visible light 4. trace metal catalysis due to Fe2+, Cu2+
45
describe the effect of temperature on stability
1. 10 degree increase leads to a 5 fold increase in decay 2. storage conditions 3. moisture content - eg. if insulin is frozen, leads to inactivation
46
give an example of an oxidation reaction
ascorbic acid-- dehydroascorbic acid
47
describe the effect of oxidation
oxygen or trace metals can lead to free radical production - analyse compound using analytical method
48
describe the effect of acid or base on drug stability
1. drug stability usually between pH 4-8 2. drug solubility at low or high pH can lead to drug instability 3. to test stability, pH 1,3,5,7,9 and 11 at 37 degrees and in presence of 1M HCL and 1M NaOH 4. Acid causes isomeric changes - eg conversion of cis isomer-- trans isomer
49
what are the effects of photodegradation
1. UV catalysed 2. often seen with storage instructions 'keep away from direct sunlight' 3. 300-400nm most damaging 4. retinol and b carotene undergo oxidation
50
what are the advantages in analysing the effect of UV light
1. to understand the effect of light on the drug 2. can be used for further drug development 3. choice of suitable packaging containers
51
what technique can be used to analyse molecular structure in solid state stability
FTIR, NMR
52
what technique can be used to analyse crystal structure in solid state stability
scanning electron microscopy
53
what technique can be used to analyse particle size in solid state stability
laser diffraction, seiving
54
what technique can be used to analyse polymorphism in solid state stability
DSC
55
what technique can be used to analyse melting point in solid state stability
hot stage microscopy
56
what are the 2 major applications of microscopy and macroscopy
- crystal morphology - particle size analysis
57
what is particle size critical for
critical for dosage forms
58
what can storage cause
1. aggregates 2. size and shape can increase or decrease 3. effect of other excipients on crystal structure 4. change in bulk density 5. change in angle of repose
59
outline the different routes of administration
- oral - topical - parenteral - nasal/pulmonary - eye - ear - rectal and vaginal
60
give examples of oral dosage forms
- solutions - syrups - suspensions - emulsions - tablets - capsules
61
give examples of topical dosage forms
- creams - ointments - pastes - gels - lotions
62
give examples of parenteral dosage forms
- injections - implants - dialysis solutions
63
give examples of nasal/pulmonary dosage forms
- solutions - inhalations - aerosols - sprays
64
give examples of eye dosage forms
- solutions - ointments - creams
65
give examples of ear dosage forms
- solutions - suspensions - ointments - creams
66
give examples of rectal and vaginal dosage forms
- suppositories/pessaries - powders - solutions -ointments - cream
67
what are the factors involved in dosage form design
1. biopharmaceutical considerations - drug absorption - route of administration 2. physicochemical properties of drug 3. therapeutic considerations - clinical indication - patient compliance
68
give examples of drugs which have multiple dosage forms
- metronidazole, prednisolone, paracetamol, lidocaine
69
what is an excipient
an inert substance that is used as a diluent or vehicle for preparing a drug product
70
what are the different types of excipients
1. solvents- water 2. flavours 3. sweeteners (saccharin) 4. preservatives (parabens) 5. stabilisers (antioxidants) 6. diluents or fillers (starch) 7. binders (gelatin) 8. anti adherents or lubricants (magnesium stearate) 9. coating agent (sugar solution) 10. disintegrating agents 11. pharmaceutical bases (white soft paraffin)
71
how do we know which excipients can be used
using the Handbook of pharmaceutical excipients and FDA guidelines
72
what are the factors affecting excipient usage
1. suitability for the dosage form - liquid paraffin not suitable for IV formulations 2. recommended concentration 3. compatibility with the drug - drug should be soluble/miscible 4. drug stability in the presence of excipient 5. effect on bioavailability 6. pharmacokinetic considerations
73
what are excipient incompatibilities
chemical incompatibilities - interaction of preservatives with non ionic surfactants reduces its antimicrobial property - interaction of carbomer with ionisable drugs leads to precipitation of gelling agent
74
what must always be considered when performing formulation development
patient compliance

PY366 Drug discovery (15 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions