Test 8 Stability/ Reg Aspects In DD Flashcards
General rule of decomp for pharma products
All pharma products decompose
What is decomposition
Less active or worse compared to parent drug
Three types of decomposition and explanation
Chemical- change in chemical structure of API or excipients mediated by temp/moisture/ light and oxygen
Physical- change to how it looks, colour smell texture etc
Microbial- microbes colonise - spoilage of drugs
True definition of FDA for stability
Ability of API and ingredients to stay in set limits for identity/strength/ purity for period of time
Define instability
Change in physical appearance & undesirable change in performance e.g bioavailability/ dissolution
When is stability assessed
Its continuous from preformulation to stage 4 clinical trials
Define shelf life
Time product stays in its chemical/ physical/ microbial stable in correct storage
What is expiry date
When shelf life ends and drug is unsafe for use
3 types of chemical stability
Hydrolysis
Photolysis
Oxidation
In relation to stability, what happens in hydrolysis
Splitting by water or breaking bond with water
Which functional groups are most prome to hydrolysis
Ester
Amides
Give examples to hydrolysis reactions and drugs
Aspirin
Chloramphenicol
Diamorphine hydrochloride ampoules
Penicillin
In relation to stability, define oxidation
Loss of hydrogen or addition of oxygen
Increase C=O bonds OR
decrease C-H bonds
Give examples of drugs that undergo oxidation reaction
Phenols
Catecholamines
Polyunsat fats
Ascorbic acid
In relation to stability, define photolysis
Decomposition by light, change in potency and affect appearance of formulation
Eg ketoprofen
Complete sentence…
Rate of photodegradation depends on
Rate of light absorption
What is physical stability
No change to appearance or organleptic properties etc
Why is physical stability significant
Affect pharma elegance, drug uniformity, bioavailability
Likely physical instability and effects of formulation
Precipitation, crystal growth, polymorphic changes
Leading to
Loss of uniformity, affect’s bioavailability, injection of precipitated drug is painful
Physical instability and effects of suspension
Settling
Caking
Crystal growth
Leading to
Loss of uniformity
Bioavailability
Loss of elegance
Physical instability and effects of emulsions
Creaming. Coalescence. Breaking
Leading to loss of uniformity , affect bioava’ , loss of elegance
Physical instability and effects of tablets
Changes in disintegration time, dissolution profile, hardness, appearance
Leading to chnage in drug release, affecting bioavailability
Microbial instability
Must not suffer microbial attacks
Must have same contamination and sterility
Protection against instability
Buffering agents
Protection from light
Antioxidants
Reformulation
Preservatives
Free radical scavengers
Define zero order
Rate of reaction independent of concentration of reactants
If half life is 0.693/k what does it show
Plot of algorithm of drug remaining against time linear
When concentration is vs time, what is it
Zero order
What is the most common type of drug degredation
Hydrolysis
What is the second most common type of drug degredation and what is most susceptible
Oxidation
C=C most susceptible e.g polyunsat fats
The MHRA rules that all drugs must be
Good quality
Safe
Effectice
Whats the main role of regulatory affairs
Protect public health
Briefly list non clinical disciplines of DD
Test invivo & invitro safety and efficacy
Develop pharm profile and toxicity from at least 2 animal species
Asses toxicity from 2 weeks to several months
Quality of reporting of data
Factors validating to quality products must be..
Interactive and take all into consideration MUTUALLY
List factors validating to quality lroducts
Personnel
Validated process
Procedures
Equipment
Premises
Environment
Packing materials
Raw materials
What is GLP
Good lab practice
Guidelines for lab, studies must be safe planned monitored and archived
What does the GLP certify
Whether every step is valid, QA, heavy emphasis on recording data
Principles of GLP
Test systems
Facilities reporting of everything
Storage and retention of records/ materials
What is GMp
Good manufacturing practice
Consistent high quality products, appropriate for intended use
Meet marketing authorisation
What can happen if GMP is not followed
Adulteration where drug does not meet safety, identity, strength quality and purity of products
What are the two types of GME
Personal- prevent contact with dusts/fume/ acceptable comfort condition
Environment- avoid dust discharge/ fume discharge/ effluent discharge
Product- no cross contamination, protect from ambient conditions, prevent contamination of staff/ correct temp& humidity
What can uncontrolled environment cause
Product degredation & contamination = loss of product/ profit
What are contaminats
Products other than manufactured products
Examples of contaminants
Foreign objects
Particulate matter
Microorganisms
Endotoxins (degraded microorganism)
What is GCP
Desgining conducting recording and reporting of studies
What does the GCP set
Minimum quality standards, regilatiosn and guidelines for conduct of research
Main outcome of ICH
safety, quality, efficacy , unify reg requirements for new products
Reduce DD cost & time
Principles of ICH GCP
Conducted in accordance to ethical principle e.g decleration of helinski
Weigh risks and benefits before trial
Clinical/non clinical must be weighed to support trial
Good distribution practice GDP
Wholesale distribution, quality, integrity of meds can be affected by lack of comtrol
Meds need to be obtained from licensed chain
Stored transported and handled under suitable conditions
QA controlled
List Determinants of medicine qualtiy
Identity- api
Purity- uncontmainated
Potency- 90- 110 of labelled amount
Unifromity- consistent colour shape size
Bioavailability- interchangeable product- different forms
Stability- medicine active for stated period
Who ensures medicine quality
Pharmacy
Drug reg authority
Hospital
Pharmacist
Physicicians
Tests gor liquid dosages
Uniformity of dose
Contents
Stabikity
Sedimentation volume
Test for solid
Tablet hardness
Friarbility test
Diameter thickness
Weight variation
Disintegration
Tests for capsules
Moisture content
Single wall thickness
Dissolution
Visual inspection
