Practical experiments questions Flashcards
Why are direct UV measurements and titration only limited for stability testing analysis
Both methods are not specific enough for the quantificantion of both DP and DS
in the case of UV, structure of the both degradation and drug product should be similar. Therefore absorbing in a similar range, but the DP could have a higher extinction coefficient
What are two characteristic which are importnat for precise stability data in a analystial method
define both characteristic
Specific and senstitv
Specific enough to determine the drug substance, the impuries and degradation products
Sensitiv enough to determine smallest amount
Why is the TCL method for the purity of essential oils still in the pharmacopioa
Due to the complex composition of the essential oils, its not easy to used analytical methods such as HPLC or GC to detect the degradation products of essential oils
Which methods are possible
HPLC with refractive index detecor or photodiade array detectors (DAD)
GC-MS as detector
Container colusre system for essential oils
amber or opague, with low oxgen transmission
Why are the stability of essential oils important
Essential oils are used as medinical products.
also in food as antioxidance and preservatives
Importance of the acid value
it is a physicochemical property of essential oils
An incremnet in the amount of free aicd is indicative hof hydrolysis, more amount of KOH, NaOH.
What happend to essential oils when not well stored?
Its degrades to free acids, through oxidation , polymerisation of resignication reaction.
Used of acid value
it is to assess the quality of the product and suitability for the oil
What are typical DP functional groups of essential oils?
Alcohols, keton, aldehye epoxis
What is refractive index?
it is used to dtermine the speed of light when passing through the oils
In which development phase stability studies are carried out and why they get more important?
In all development phases, starting from the drug susbtance itself ( stage 1), preformulation and formulation for toxicology and clinical studies (tage 2), then with the selected formulation (stage 3).
stabiliyt studies with registration batch and production batch and as well with the continous production (4,5,6)
After aproval there is a post aprroval changes study (7)
What is an incompatibilities
it is a physical and chemical interactions between two or more components of a preparation which can have an influence on the stability of the formulation
Why stability studies must be carried out
it is to provide evidance on how the quality of a drug susbstance or DP varies with time under influence of a varity of enviromental factors such as temperature, humidity and light
what is a Maillard reaction?
API with primary amine, which are incompactibale with mono and dissacharides (e.g lactose)
Ester hydrolysis
AAS with magnesium hydroxide
Whats the aim of stability test
it serve to determine the period during which the drug product retains its specification (expiry date)
Which stability study is the most important one during development
Studies witth the resistration application, only results that have already been collected should be confirmed
What is based on the results from stage 4
the shelf life statements
What is Matrixing?
A selection subsets of all stored samples
What is based on the results from stage 4
the shelf life statements
What is Matrixing?
A selection subsets of all stored samples analysed at an examination date. the results of the subset are representative for all samples at the time of the examination
Which factors can be included Matrixing?
different batches, strenght, sizes of the container closure system
Bracketing
Only the extrems of certian design factors are tested at all time points. the assumption that non-audited ones show the same stability behaviours as the two extremes
when are structure identification necessary?
when degradation product present at a level greater than (>) than the identification threshold
When can the Arrhenius plot be used?
When storing samples at different temperature and determineing the content of the samples at predefined time point
whats emuslifier used for?
To reduced the interfacial tension by forming a film at the water/oil interface
Creaming
Separation of emulsions into its two parts, less dense part(cream) and the other parts.
What’s the main characteristics to define emulsions?
Droplet size distribution
why do we need a emulsifier with a high viscosity
it creates a high viscous interfacial films, which reduces coalescence by decreaseing the velocity of the particles
Definition of coalescence
it is a porcess where the distance between two or more separated groups of miscible particles become smaller, pulling each other to reach the slightest contact
Order the formulation syrup, for oral, eye drops , tablets and ointments for cutaneous for microbial contamination
Tablets, syrup for oral,ointments, eye drops
Ionic interactions in aqueous systems
Salt formation leads to decreases dissoziation
Why can incompatibilities have influence on the microbial stability?
Because the prevervative can lost its effectivness to preserved the formulation..This will lead to grwoth of micro-organismen over time
when happend when an anion API is stabiliert with cation surfactant
Cation-anion interactions, decreased hydration/solubility
When can precipitation occur?
of water-soluble compounds by addition of water-miscible solvents (ethanol)
When happend with the an aqueous solution in glas as primary packaging material
Ion release into aqueous media, this could be alkali and alkaline earth metals, leading to alkalization of aqueous solutions
Glas as PP
Drug adsorption on the glas surface, important by low-dose and proteins
Plastic and metal as PP
Migration of APIs into elastromer or the corrosion of metal can cause metal cations to dissolve
Urea and water formulation
Urea decomposes slowly in the aqueous solution, the reaction is accelerated by a pH increase durig decomposition (Buffer, pH 4-5)
Why do we used the MKT?
it is used in storage and distribution applications, especially where there can be fluctuations, either because of the climatic zone or the season
Why do we used the Degradation product for calibration
because the increase of the degradation product, will results to a highe Area under the curve than the decrease in the API itself
Why is the Arrhenius equation important?
it describe the effect of temperature on the stability of an API. Therefore, once can conduct stress study at higher temperature. And by using the Arrhenius equation, the shelf-life of the product at a giving temperature can be calculated
Why is moisture and temperature a critcal parameter for the stability of a drug?
Moisture brings moleules closer together and heat icrease the reaction rate
What’s the different between drug-excipients and drug-moisture incompatibility?
drug-excipients is when the drug interacts with the excipients, where the drug-moisture is cause due to th exposual to high moisture content
Why is ASA incompartible with Mg sterarte?
Mg sterate has a higher solublity in acetylsaliclylic acid, which leads to the formtion of a buffer, creating a solvated ASA. the created pH enviroment is what is detrimental to the stability of the ASA
What about the Polyethylen glycol with ASA
What’s the reaction?
ASA as well undergo a pseudo-first order decomposition
Trans-esterification of the slicyclic acide and acetylated PEG
the ph value at which a substance precipitates depends on
on the pka value, concentration of the substance and the solubility of the compound
which equation is used to calculate the protoned state of a compound?
Henderson-Hasselbalch equation
Why do we better quanify the DP and the API itself?
The decrease of the API content will be visualised as a small change in the AUC compared to the increase of content of the DP (1%–>2%). the 100% increase in the AUC is more accuratly rocorded.
On what does the elute of the component in the HPLC depends?
it’s depends on the component differential affinity between the stationry and mobile phase
Example of the stationary phase
normal phase, reverse phase column (RP 18)
and reverse phase (RP 8)
The responsible of the mobile phase
the MP is responsible for eulting the sample components through the column
On what does the speed and degree at which the compound moves depends?
it depends on its solubility in the mobile phase. Higher solubility in the MB leads to faster elution out of the column
What kind of composition of the MP do you know and when are they used?
Isocratic and gradient mobile phase.
gradient phase is used when both compound have similar interaction with the SP
How does the ph of the MP affects the speration
its effect the shape of the peak
How does the ph of the MP affects the speration.
explain with ASA and SA?
low ph will shift the equilibrium of the SA to the protonated state, wherby higher ph will result in the stabilisation of intar-molecular hydrogen bonds
Why is methanol added to the MP
it is to reduced the space(time) between the peaks on the chromatogram and speed speration process
What are fatty acids?
give an example
fatty acids are carboxylic acids with a carbon chain
omage 3 and 6
name the three groups of the FA
- carboxylic acids with long saturated aliphatic carbon chains
- carboxylic acids with long unsaturated aliphatic carbon chains
- CA with carbon chains which also includes further functional groups
