L30 Pre-formulation TJ and GT Flashcards
Preformulation is defined as
The process of gathering all the parameters that influence the choice of formulation.
Outline the drug discovery steps
Target identification -> target confirmation-> hit -> hit to lead -> lead optimisation
Outline the drug development steps
Preclinical studies -> volunteer studies -> phase II clinical trials -> phase III clinical trials -> scale up for launch.
Name three important physicochemical properties that influence rate of permeation
Temperature, viscosity and density
List the different types of stability testing
chemical stability test Temperature + Humidity(i.e solid state) testing photostability test pH dependent stability in solution oxidative stability
how does chemical stability testing work?
A drug can be tested under acidic or alkaline conditions:
- Under acidic condits: reflux with 0.1 mol HCL for 8-12 hrs
- Under basic condits: reflux with 0.1mol NaOH for 8-12 hrs
How does solid state testing work?
The test assess the effect of the solid state form (amorphous vs crystalline)
Pre-weighted samples placed in stability cabinets at:
40 degrees
60 degrees
25 degrees + 85 degrees relative humidity (open vials)
40 degrees + 70 degrees relative humidity (open vials)
OVER a 2,4 and 8 week period.
At pre-determined time intervals, a sample is taken from each cabinet and dissolved in an appropriate solvent. This is then analysed under HPLC to identify if any degradation has occurred.
Note: HPLC method is usually Reverse phase HPLC
How does photostability testing work?
Drug samples are stored in high intensity light/UV condits @ 25 degrees in photostability cabinets.
The ICH guidelines state that the drug should be exposed to 1.2million lux hours.
Drugs stored @ different concentrations in various solvents.
The controls are protected from light but ONE stored under the same conditions as the sample.
Describe how pH testing in solution works
A solution of the sample is produced. The temperature is kept at 37 degrees. The PHs being investigated involve pH 1/4/7/8. They are kept for 1day-1month.
State the two types of oxidative stability testing available.
1: Using Free-radicals
2: Using molecular oxygen
explain oxidative stability testing using free radicals
This involves Initiation, Propagation, Termination. It can be catalysed by heat, light, radicals or the presence of metals.
Note: the degradation route may be dependent on temperature, so using high temperatures might not accurately reflect what occurs at ambient or room temperature
explain oxidative stability testing using molecular oxygen
Molecular oxygen diffuses through the crystal lattice to the labile sites.
Excipient compatibility can be assessed using DSC. If there are any unexplained exothermic processes, its due to excipient incompatibility
what properties are based on the physical state of the solid?
particle size
favourability
compression characteristics
What is hygroscopy
The phenomenon of molecules attracting or holding water from their surroundings.
why is stability testing important?
to provide feedback for the modification of labile groups to:
- Improve stability
- Help scientists determine how easily the compound can be developed
- Provide guidelines for product handling and storage
- Provide information to guide stabilisation strategies