L30 Pre-formulation TJ and GT

Question 1

Preformulation is defined as

Answer 1

The process of gathering all the parameters that influence the choice of formulation.

Question 2

Outline the drug discovery steps

Answer 2

Target identification -> target confirmation-> hit -> hit to lead -> lead optimisation

Question 3

Outline the drug development steps

Answer 3

Preclinical studies -> volunteer studies -> phase II clinical trials -> phase III clinical trials -> scale up for launch.

Question 4

Name three important physicochemical properties that influence rate of permeation

Answer 4

Temperature, viscosity and density

Question 5

List the different types of stability testing

Answer 5

chemical stability test
Temperature + Humidity(i.e solid state) testing
photostability test
pH dependent stability in solution
oxidative stability

Question 6

how does chemical stability testing work?

Answer 6

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

Question 7

How does solid state testing work?

Answer 7

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

Question 8

How does photostability testing work?

Answer 8

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.

Question 9

Describe how pH testing in solution works

Answer 9

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.

Question 10

State the two types of oxidative stability testing available.

Answer 10

1: Using Free-radicals
2: Using molecular oxygen

Question 11

explain oxidative stability testing using free radicals

Answer 11

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

Question 12

explain oxidative stability testing using molecular oxygen

Answer 12

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

Question 13

what properties are based on the physical state of the solid?

Answer 13

particle size
favourability
compression characteristics

Question 14

What is hygroscopy

Answer 14

The phenomenon of molecules attracting or holding water from their surroundings.

Question 15

why is stability testing important?

Answer 15

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

Question 16

what are ICH guidelines saying?

Answer 16

the drug should be tested under different stress conditions that will be indicative to the conditions the drug will be exposed to.

Question 17

instability within drugs can be caused by

Answer 17

Isomeration and polymerisation