Photodegradation of indomethacin and naproxen contained within commercial products for skin - RAP.

ABSTRACT

Patient can be exposed to the photodegradation products of a drug after skin application of topical formulations. NSAIDs, with analgesic and anti-inflammatory properties, are known for the potential photoinstability, and are applied often in the form of creams, gels or liquids, commonly used among athletes, elderly people, geriatric patients and patients treated with multidrug therapies. Susceptibility to photodegradation hazard of those group arises the need for development of a new approach, with the ability to evaluate the patient safety. We planned to use a rapid assessment procedure (RAP) of safety by testing the photostability of popular skin medicinal products. This method, proposed many years ago by WHO, is now reintroduced to analytical applications in industry, when emergency drugs (e.g. for Covid) are implemented to the market in accelerated procedures. In the health care system, qualitative evaluation of drugs is extremely valuable, therefore we have planned to identify photodegradation using the FTIR method - infrared spectroscopy and DSC - differential scanning calorimetry, whilst the risk of formation of genotoxic products using the Ames test. We have successfully demonstrated that changes in the chemical structure and physical form of both pure APIs and drug products containing the API be assessed in a short time. Another advantage of our work is the combination of the developed results from FTIR/NIR spectra with statistical analysis. As a result, full and quick qualitative assessment of the effects of photoexposure of selected NSAIDs is performed, fortunately showing no mutagenicity. Due to the popularity of NSAIDs applied to the skin, a gel containing naproxen and spray with indomethacin were selected for testing. The analysis carried out for various formulations of both preparations allows us to demonstrate the universality of the applied RAP methods in assessing the risk of hazard to the patient, thus we present research results that expand or widen the knowledge and assessment of risks related to the use of drugs on the skin.