API Stress Testing Studies

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Stress testing or forced degradation has long been recognized by the pharmaceutical industry as an important part of the drug development process, especially in relation to purity by controlling stability. Protheragen-ING provides professional stress testing services for evaluating the stability of Active Pharmaceutical Ingredients (APIs) and their formulations. The studies are conducted to ensure the quality, stability and safety of pharmaceutical products.

Fig.1 API Stress Testing Studies.

What is a stress testing study?

Stress testing (also known as a forced degradation study) is a technique used to study the stability of APIs. In this context, "stress" refers to any physical or environmental conditions that the product will encounter that may cause a chemical change.

The main findings of stress testing include:

Assessing the stability of molecules.
Establishing possible degradation pathways and products.
Validation of analytical methods used to assess chemical stability.
Gain insight into pharmaceutical packaging and storage.

Typical Forced Degradation Experiments

Protheragen-ING employs a variety of stress conditions to evaluate the stability and degradation pathways of APIs. The selection of stress conditions is based on scientific rationale and is intended to mimic or accelerate the degradation processes that APIs may encounter during their shelf life or storage conditions.

The following are some common conditions used in stress testing studies.

Temperature	APIs are exposed to elevated temperatures to accelerate the degradation process. Commonly used temperature conditions include 40 ℃, 50 ℃, 60 ℃, and higher, depending on the stability characteristics of the API.
Humidity	APIs can experience high humidity conditions to evaluate their sensitivity to moisture. Humidity levels of 75% relative humidity or higher are commonly used in stress test studies.
Oxidation	APIs may undergo oxidative degradation under conditions that promote oxidation. Oxidative stress conditions involve exposing the API to oxidants or elevated oxygen levels to assess oxidative susceptibility.
Acid/Base Hydrolysis	Acidic or basic conditions may stress drug molecules. Conditions range from 0.1 M HCl and 0.1 M NaOH.
Light	Exposure to light, particularly ultraviolet (UV) and visible light, is used to assess the photosensitivity of APIs. Conditions typically involve exposing the API to a specific intensity and duration of light.
Moisture	APIs may be exposed to moisture to assess their hygroscopicity and moisture-induced degradation. This may involve direct contact with liquid water or humid environments.
Thermal Cycling	Thermal cycling involves cycling the API through multiple temperature changes, typically between high and low temperatures, to simulate real-world temperature fluctuations and to assess their effect on API stability.

Common Analytical Techniques

Protheragen-ING employs a variety of analytical techniques to characterize degradation products and assess API stability. Below are some of the common analytical techniques we use for API stress testing:

High-Performance Liquid Chromatography (HPLC): HPLC is one of the most widely used techniques for the separation, identification, and quantification of degradation products.
Gas Chromatography (GC): Used to analyze volatile degradation products.
Mass Spectrometry (MS): MS is often combined with HPLC or GC to provide structural information about degradation products.
Fourier Transform Infrared Spectroscopy (FTIR): Used to analyze the functional groups present in the sample and to detect changes in the chemical structure of the API during degradation.
Nuclear Magnetic Resonance (NMR) Spectroscopy: Used to elucidate the structure of degradation products and to confirm their identity.
Ultraviolet Spectroscopy (UV-VIS): Used to monitor changes in the absorbance of API solutions over time, indicating the formation of degradation products or changes in the API chromogenic group.
Thin Layer Chromatography (TLC): Used for qualitative analysis and separation of degradation products.

Fig.2 Albendazole drug stress test. Fig 1. Albendazole drug stress test^[1].

If you are interested in this service and need more information, contact us and we will arrange for professionals to provide you with more information and discuss your specific requirements.

Reference

Ardila JA, et al. "Design of experiments applied to stress testing of pharmaceutical products: A case study of Albendazole." European Journal of Pharmaceutical Sciences. 2021, 165, 105939.

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