Product degradation studies are an important test for any pharmaceutical or other high value active material. These experiments generally expose the material to an external stress to assess the stability of the constituents or formulation. External stresses may include temperature, pH, light, moisture, and even exposure to other materials within the product formulation, and their degradation products.
Conventionally, degradation tests can take very long periods of time, because standard testmethods require the materials to be exposed to stress factors for periods of weeks or longer, andthen tested using standard analytical methods.
Accelerated testing is of clear benefit. Use of elevated temperature to increase the rate ofinteractions is the most powerful factor to shorten the length of time required for these tests.However, conventional batch techniques are of limited use for such accelerated testing, as theapproach is not readily amenable to carrying out a wide range of tests at varying temperature and storage time. It is also difficult to achieve temperatures near or beyond reflux without specialprecautions; achieving such temperatures is typically required to achieve significant rateacceleration.
An ideal forced degradation test system would have a number of useful properties:
- Ability to accelerate tests by a factor of 10 to 100 fold or more (e.g. 1 hour to 1 minute = 60 fold)
- Requires holding sample at temperatures well above reflux
- Ability to process and manage multiple samples under multiple times and temperatures
- Requires sample introduction, tracking and storage capability
- Ability to introduce a range of contaminant materials
- Requires injection and mixing systems
- Ability to introduce other stresses
- Requires capability to expose to light, etc.
- Ability to sample automatically and collate data
- Requires integrated analytical capability
Flow systems are ideal for this application, as they meet all of the above requirements in acompact and integrated instrument. A further benefit is that the use of microreactors allows teststo be performed with very small amounts of material, reducing cost and storage space.
This application note describes the use of an Africa flow system to conduct a forced degradationstudy on a series of Parabens (common pharmaceutical preservatives). Solutions of methyl, ethyland propyl paraben are susceptible to de-esterification in the presence of alkali. The flow reactorsystem allows several different levels of exposure to be investigated within a single experiment.Variables such as concentration, temperature and reaction time can be changed to determine thestability of the paraben. A major advantage of the Africa flow system is that the pressureregulation of the system means that temperatures beyond the boiling points of reaction solventscan be used. In these experiments the concentrations of the reactants was held constant whilstboth reaction time and temperature were varied.