Synthesis and photodegradation studies of analogues of muscle relaxant 1,4-dihydropyridine compounds

Abstract

This paper describes the synthesis of 1,4-dihydropyridine compounds (DHPs) endowed with good muscle relaxant activity and stability to light. Six new condensed DHPs were synthesized by the microwave irradiation method. A long-chain ester moiety [2-(methacryloyloxy)ethyl] and various substituents on the phenyl ring were demonstrated to aff ect the muscle relaxant activity occurring in isolated rabbit gastric fundus smooth muscle strips. Forced photodegradation conditions were applied to the molecules according to the ICH rules. The degradation profi le of the drugs was monitored by spectrophotometry coupled with the multivariate curve resolution technique. Formation of the oxidized pyridine derivative was observed for all the studied DHPs, except for one compound, which showed very fast degradation and formation of a second photoproduct. Pharmacological tests on the molecules showed a good muscle relaxing eff ect, with a mechanism similar to that of nifedipine, however, proving to be more stable to light.

A New Generation of Dihydropyridine Calcium Channel Blockers: Photostabilization of Liquid Formulations Using Nonionic Surfactants

“…In any case, the photodegradation process involves the total loss of the therapeutic effect. Unfortunately, it is also known that the photodegradation of the DHP drugs leads to a significant production of singlet oxygen, superoxide, or both of them, which in most cases are responsible for photosensitive/phototoxic effects [14,15,16].…”

Evaluation of Photostability of Medicines and Development of the Photostabilization of the Photosensitive Medicines

“…Several studies indicated that the main photodegradation pathway of dihydropyridine drugs such as amlodipine and nifedipine was the oxidation of dihydropyridine rings resulting in the generation of pyridine derivatives [39][40][41]. However, as shown in Fig.…”

Efficacy of Red Glass in Protecting 1,4-Dihydropyridine Antihypertensive Drugs in Liquid Formulations

“…Several approaches have been proposed to design liquid pharmaceutical formulations of DHPs: addition of excipients with large absorption regions, incorporation in supramolecular matrices as liposomes or cyclodextrins, and incorporation in microspheres or nanocapsules [18,19]. A different approach involves the synthesis of new DHP structures more stable to oxidation [20]. However, today the adoption of dark glass or plastic containers remains the most common method used by the pharmaceutical industry to protect photosensitive drugs.…”