"Gel formulation of Nabumetone and a newly synthesized analog: Microemulsion as a photoprotective topical delivery system" in PHARMACEUTICS AND ADVANCED DRUG DELIVERY SYSTEMS

Introduction: Nabumetone is a non-acidic nonsteroidal anti-inflammatory drug that is rapidly metabolized in the liver and undergoes extensive photodegradation. Photostability studies were performed on topical formulations containing this drug and a new analog, synthesized in order to reduce the light- sensitivity and to improve the pharmacokinetic profile. Methods: Stability tests, according to the International Conference on Harmonization rules, were applied on ethanol solutions and topical gel formulations of both compounds. The photodegradation profiles were monitored by Multivariate curve resolution applied to the UV spectral data. The inclusion of the compounds in microemulsion was investigated to improve light stability and, at the same time, to ensure a sustained release system for skin delivery. All the formulations in solution, gel, microemulsion, and microemulsion-in-gel were exposed to forced irradiation of 350 W/m2, corresponding to a 21 kJ/m2 min, for up to 300 min. Results: Photostability increased significantly for both drugs in the liquid microemulsion and microemulsion-in-gel, compared to the ethanol solution and plain gel, reaching a residual drug of 97% and 98% for Nabumetone and analog in microemulsion-in-gel, respectively. Permeation experiments on the microemulsion-in-gel showed a better performance of the analog formulated at 0.2%, compared to the same formulation of Nabumetone at 0.7%. Conclusion: The overall data demonstrated that the developed formulations are effective for controlled topical delivery of the tested compounds along with the use of lower drug doses leading to reduced side effects. This approach could be extended for the preparation of innovative local or systemic pharmaceutical formulations.