Test 7 Emulsions/ Flashcards
What is the name of two things that totally mix
Solution
What two things are needed to make a solution
Solute and solvent
Factors that suggest that suspension is unstable
Aggregation
Sedimentation
Substance distributed
Dispersed phase
What is another name for vehicle
Dispersing phase or dispersing medium
What makes a dispersed system
Dispersed phase and dispersing medium
List desirable properties of oral suspension
No grittiness
Uniform dispersion
Easy to pour but not watery
Particles should settle slowly
Readily redispersed when shook
Flocculated suspension
Palatable, good odour and colour
Insensitive to temp
Desirable suspeensions for injections
Synringeabiltiy
Sterile
Desirable characteristics for opthalmic susp
Smaller than 10um
Sterile
Desirable characteristics for topical
Fine particles avoid grittiness
Describe sedimentation behaviour
Settling of particles/floccules due to gravity
Ways of decreasing velocity
Smaller particle size
Increases viscosity and density of dispersion medium
Decrease density if dispersed phase
How do we ensure that a suspension is permanently well dispersed
Ask patient to shake bottle
Relationship between particle size wnd velocity
Directly proportional
Relationship between density dispersed and dispersion media wnd velocity
Directly proportional
Relationship between viscosity of dispersion medium wnd velocity
Inversely proportional
Define deflocculation
No flocs dominating repulsion forces
Define flocculations
Flocs formed attracting forces dominate
Repulsive forces are a result of
Electrostatic forces
Describe the effect of neutral forces in APIs
More van der waals attraction that electrostatic = form flocs
Describe the effect of charge in APIs
Electrstatic forces dominate=deflocs= cannot be easily redispersed due to repulsion
How would you know the difference between a flocculated and deflocc solution by looking at it
Flocc top layer will be clear
Defloc top layer cloudy
In a deflocc solution why is the top of the solution cloudy
Due to repulsive forces, and stokes law, sedimentation of larger psrticles happens first
Explain flocculation
Weak bonds forming fluffy conglomerates
Settle rapidly but will jot form a cake
Easily resuspended
Clear supernatant
Describe the speed of flocculated suspension
More rapid than deflocculated
What dies sedimentation depend on
Size and porosity if flocs
Describe energy in deflocculation
High repulsive energy
Aggregation of particles in deflocculation
Caking
Describe supernatant in deflocculation
Turbid supernatant
Describe speed of sedimentation in deflocculation
Rate of sediment slow with larger particles sedimenting first
In flocculated suspensions what particles settle first
All particles of size settle at same speed
In terms of particles explain the difference between flocculated and deflocculated system
Defloc remain independent
Flocc particles link together to form loose structure
In terms of sedimentation state the difference between floc and defloc solution
Floc - all sediment at same speed in loose structure
Deflo- large sediment first but slowly
In terms of supernatant describe different between flocculated and defloc system
Defloc- supernatant turbid for long time
Floc- supernatant quickly becomes clear
In relation to dispersion, compare floc and defloc system
Defloc- may form hard cake irreversible
Floc- sediment remains loose and easy to redisperse
What does the sediment volume of ratio show
Qual knowledge physical stabiliy of suspension
Equation for sediment of volume ratio
Volume of sediment /total volume
How can flocculation be controlled
Electrolytes- electrostatic stabilisation
Polymers - steric stabilisation
How are electrostatic electrolytes used in cotrolled flocculation
Electrolyte decrease the zeta potential
How are polymers used in controlled flocculation
Work by absorption Hydrophilic polymers such as cellulose alginates acacia gelatin sodium oleate
Which forces lead to attractive interactions between two identically charge oarticles
VDW
A flocculated suspension is associated with
A large sediment volume and a clear supernatant
What property is a characteristic of deflocc suspension
Close packing of sediment to form a cake
What will enhance yhe stability of a drug suspension
Reducing particle size and increasing the viscosity of the suspension
How are drugs approved
Benefits are deemed to outweigh their risks
Are drugs safe
No all drugs have risks many are serious
Do OTC drugs have risks
Yes although fairly rare
How does the patient evaluate benefit and risks
Personal values
How does the HCP evaluate benefit and risks
Risks for the patient
How does the MHRA evaluate benefit and risks
Risks for population
What does the mhra stand for
Medicine and healthcare product regulatory agency
Describe the rofecoxib scandal
Approve for arthiritis but increased risk if heart attack
Explain the effect of drug advertising on individuals
More exposure to meds which gives an impression of greater safety than actually exists
Take meds to maintain health
Definition of adverse drug reaction
Any harmful effect caused by admin of drug at NORMAL DOSAGE during NORMAL USE
Define risk/benefit ratio
Exposure to personal risk is recognise as a normal aspect of everyday life. We acceprs a certain level of risk in our lives as necessary to aschieve certain benefits
Frequency of ADR
Very common
10% or 1 in 10
Frequency of ADR
Common
1% to 10%
1 in 10 to 1 in 100
Frequency of ADR
Uncommon
0.1% to 1%
1 in 100 to 1 in 1000
Frequency of ADR
Rare
0.01 to 0.1
1 in a 1000 to 1 in 10,000
Frequency of ADR
Very rare
Less than 0.01% to less than 1 in 10,000
What is pharmacovigilance also known as
Post marketing surveillance
Major goal of pharmacovigilance
Detect a signal on an unkowm serious adverse drug reaction ASAP
Obtain additional info unknown to marketing
Effect of pharmacovigilance on labelling and pateint
Improve labelling of drug
Improve patient care and patient safety
Limitations of clinical trials
Limited no of patients
Narrow population
Narrow indications
Short duration
No pregnancy
Concomitant meds controlled
What action can be taken from pharmacovigilance findings
Restriction in use
Changes in dose of med
Introduce specific warning
Change legal status of med from otc to pom
Product recall
International collabs for reporting meds
WHO
Eu union- EMA
Fda in us
Uk MHRA- yellow card scheme
Where are yellow carss completed
Online and in the BNF
What does rhe yellow card scheme act as
Early warning system for identification of unrecognised reactions
What does the yellow card scheme collect information from
Side effects
Medical devices
Defective meds
Fake meds
Safety concerns from e cigs
What ADRs should be reported
Death or serious illness
Minor risk with new medicine
Minor risk if associate with a child or in pregnancy
What does black triangle mean on BNF
New Drug monitored closely for minimum of two years black triangle not removed until safety of drug is established
ADR can result in the following:
Result in death
Life threatening
Requires hospitalisation
Disability
Congenital anomaly or birth defect
Medically significant
Who can report ADRs
Patients /relatives
HCPs
Pharma companies
Authority
Any member of general public
What does pharmacovigilance heavily rely in
Passive surveillance
In terms of discipline what is pharmacovigilance
Dynamic clinical and scientific discipline
How is a drug deemed successful
Promise invitro demonstrating a beneficial effect in animal and models as well as pass through 3 phases of human clinical trials
Difference between invitro and in vivo
Invitro in cells
In vivo in life
What is formulation
Putting compound in suitable vehicle
How do you test stability
Different temperatures and humidity
Making sure that nothing happens to the drug
What does phase 1 test
Safety in humans
What does phase 2 test
Efficacy in patients
What does phase 3 test
Safety and efficacy larger scale
What does phase 0 test for
Effect on body
What does phase 4 test for
Long term safety
IMPD
Investigational medicinal product dossier
Certifies approval for clinical trials to take place
MAA
Marketing authorisation application
Must be approves at the end of clinical trials
Equivalent to NDA
EMA
European medicine agency
Revies the commercialised products
Why are new drugs needed
Unmet medical need
Cost of therapy
Sustain industrial activity
Explain the unmet medical need
New diseases
Low efficacy such as dementia and cancer
Side effects of antidepressants/ antipsychotics
Purpose of drug patents
Protect ideas in pharmaceutical company
Definition of formulation science
Transforming API into a quality drug product in a specific dosage form
Purpose of formulation
For stability ease of administration or patient acceptability
What does formulating a drug and excipients into a dosage form allow
Manipulation of dosing frequency
How is choice of formulation important
When dealing with vulnerable populations eg children elderly
What does preformulation study involve
Characterisation of api eg solubility/melting point
Investigation fo physicochemical properties alone and with excipients
Choosing quant formula and process is also known as
Formulation development
Transferring the process from lab to industrial is known as
Scale up and process validation
Learning before doing is…
Pre-formulation studies
What do drug discovery and preclinical trials involve
Preformulation
Formulation support for preclinical test
Developing a formulation for clinical trials
What do clinical trials involve
Scaleup activities
Ontime supply of clinical trial material
Formulation development
Post marketing surveillance can lead to..
Reformulation
2nd generation launch
Pom to otc
Preformulation main areas of focus regarding physicochemical properties
Organoleptic properties- colour/odor/taste
Particles size and shapes-solubility
Purity-impurtities can be toxic
Surface area - solubility and dissolution
Preformulation main areas of focus regarding
Bulk characteristics
Crystallinity and polymorphism- stability and compatibility
Bulk density- measure volume / weight
Powder flow properties
Hygroscopicity- how much water absorbed from air
Preformulation main areas of focus regarding
Solubility studies
Aqueous solubility - must dissolve in git prior to absorption
Ph solubility
Log p- drug across membrane
Dissolution
Preformulation main areas of focus regarding
Stability studies
Solid state- stable storage conditions snd investigate effect of pH:/ cosolvent/ temp/light
Solution
Bulk
Compatibility - look at interaction with other drugs
What are drug candidates becoming
More lipophilic and poorly soluble
What does the comprehensive report include
Problems associated with molecule
Formulation studies involve
Delivery of robust and stable drug product formulations that consistently deliver the desired API:
List the steps of formulation studies
Formulation design
Process development
Formulation support for preclinical test
Clinical trials
Scale up
Package development
Ongoing stability studies
How did covid develop quickly
Funding
Urgency
Demand
How did covid vaccine trigger immune system
Spike protein
How did covid get approved quickly
Temp approval for specific batches of pfizer vaccine based on efficacy
Rolling revies process
Why was covid vaccine temporary
Dont need eu approval
Approval for 1 year
Allow companies to continue studies and submit evidence
Where can you find information for drug disposal
EMC
Patient leaflet
What are preclinical trials
Non clinical studies is the stage of research that begins before testing in humans
What is the purpose of pre clinical trials
Determine a products ultimate safety profile
In preclinical trials, what is the main purpose
Test drugs and devices to see if theyre safe and effective
What types of products are used in preclinical tests
New drugs
Medical devices
Gene therapy solutions
What do individuals consider before taking medication
Effectiveness
Doee
How often
Side effects
Any interactions
Is it a cure
Main aim of preclinical trials
Gather enough info to decide whether drug is safe to proceed with human trials
Animals used in preclinical trials
Zebra fish
Mice and rodent models
Rabbits
Fruit fly
List importance of preclinical trials
Determine dose, toxic dose , pharmacological action ,
Requirement if reg body
Consider ethical viewpoint
Kinetic profile
Effective route if admin
In general animal studies are conducted in two species
Rodent
Non rodent
How are safety pharmacology studies used in preclinical studies
Determine the effects of drug on specialised organ system
How are carcinogenicity studies used in preclinical studies
Determine effects of long term exposure to drug including ability to produce cancer
Not used for short term use drugs
How are reproductive toxicity studies used in preclinical studies
Evaluate effects on reproductive function & ability to produce birth defects
List the 3 types of scientific models used
Insilico- computational modelling
Invitro in test tube
In living animals
In living humans
Non animal and non humans models
In silico and in vitro
Conditions of in vitro experimentation
Aseptic techniques
Biosafety cabinet
Cells grown at 37c and 5% co2
Journey of in vitro experiment
Grow cells in flask
Then add to 96 well plate
Then plot IC50
Pros and cons of in vitro models
Less expensive than in vivo
Faster than in vivo
Difficult to mimic complex physio environments
What do screening models test in vitro models
Cytotoxicity
Protein binding
Cyp inhibition/induction
Membrane permeability
What is a model organism
Non human species studies used to provide insight into working of other organisms
Why are mouse models favoured
Close model to humans
High degree of genetic similarity
Why are c elegans favoured
Grown and manipulated with speed and ease but includes key complex features of an organism
Fruit fly
Easy to manipukaye
Used to study development, physio and behaviour
Well conserved genes -homologues
Why are Zebra fish used as animal model
Small size short life cycle
Readily produce mutations relevant to human health and disease
Embryonic development
Disadvantages of animal models
Lack of appropriate drug target in preclinical animal model
Irrelevant target
Difference in metabolism
Unethical
Animal trials…
Are not always predictive
Ethical considerations in animal studies
Refinement- minimise pain and suffering
Reduction- using a few animals as possible
Replacement- use other models
Alternatives to animal models
In vitro or computational modelling by law if as effective as using animals
Use lowest animal eg fly rather than mouse
Study details of preclinical trials
Only few out of thousands reach stage
Safety in at least two animal species
Oral and parenteral routes
What are screening test
Simple and rapid test performed to indicate presence or absence of a particle pharmacodynamic activity
What are tests on isolated organs, bacterial cultures
Preliminary tests to detect specific activity, eg antihistaminic/ antisecretory
What are tests on animal models of human disease
Animals to study different type of drugs
What is a general observational test
Drug injected in 3 doses to small group which are observed for hidden effects
What are confirmatory tests and analogous activities
Test for active compounds
What are mechanism of action studies
Attempt to find our mechanism of action
What is systemic pharmacology
Effect of drug on major organ systems
What are quantitave tests
Dose response relationship, maximal effects
What are pharmacokinetic test
Absorprion, tissue distribution, metabolism, excretion
IND
Investigational new drug
How drug is manufactured
Appears
Formulation intended
Analysis for purity/concentration and stability
Safety
Common technical document
Set of spec containing all the quality safety and efficacy information
Used with other ICh and reg agency MHRA
