L30 Pre-formulation TJ and GT Flashcards

1
Q

Preformulation is defined as

A

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

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2
Q

Outline the drug discovery steps

A

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

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3
Q

Outline the drug development steps

A

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

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4
Q

Name three important physicochemical properties that influence rate of permeation

A

Temperature, viscosity and density

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5
Q

List the different types of stability testing

A
chemical stability test
Temperature + Humidity(i.e solid state) testing
photostability test
pH dependent stability in solution
oxidative stability
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6
Q

how does chemical stability testing work?

A

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
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7
Q

How does solid state testing work?

A

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

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8
Q

How does photostability testing work?

A

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.

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9
Q

Describe how pH testing in solution works

A

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.

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10
Q

State the two types of oxidative stability testing available.

A

1: Using Free-radicals
2: Using molecular oxygen

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11
Q

explain oxidative stability testing using free radicals

A

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

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12
Q

explain oxidative stability testing using molecular oxygen

A

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

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13
Q

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

A

particle size
favourability
compression characteristics

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14
Q

What is hygroscopy

A

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

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15
Q

why is stability testing important?

A

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
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16
Q

what are ICH guidelines saying?

A

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

17
Q

instability within drugs can be caused by

A

Isomeration and polymerisation