Photodegradation of 1, 4-Dihydropyridine Antihypertensive Drugs: An Updated Review

Abstract

ABSTRACT1, 4-dihydropyridine calcium channels blockers (DHPs) are the most commonly used antihypertensive drugs. Unfortunately, these compounds have a significant degradability to light. The oxidation to the pyridine derivative represents the first, and in many cases the only, step of the degradation mechanism. The photodegradation process causes the complete loss of pharmacological activity and may trigger the formation of single and superoxide oxygen species, potentially responsible for phototoxic reactions. Several analytical techniques have been proposed for DHP determination in the presence of their photoproducts. Nowadays, DHPs are all marketed in solid formulations, especially tablets, because photodegradation is particularly fast in solution. Various approaches aimed to protect molecular integrity and therapeutic activity of these drugs from the effects of light are currently studied. This review covers the studies over the last years about photodegradation of the DHPs and the approaches to obtain photostable formulations of these drugs.

Structural studies of calcium channel blockers used in the treatment of hypertension ‐ 1H and 13C NMR characteristics of nifedipine analogues

“…One of the unfavorable features of DHPds includes their high sensitivity to ultraviolet (UV) light. During exposure to the UV radiation, an intramolecular redox reaction occurs, associated with the elimination of the water molecule and aromatization of the dihydropiridine ring that leads to the formation of 4‐(2‐nitrosophenyl)‐pyridine analogue (Figure ) . It has been proven that the rapid photochemical decomposition is related to the presence of the nitro group and its location in the phenyl ring.…”

“…Stability studies have shown that photodegradation of halogen analogues was 50 times slower compared with the compounds with the nitro group in the meta position. However, this process occurs and leads to the formation of biologically inactive derivatives of halogeno‐pyridine …”

“…During exposure to the UV radiation, an intramolecular redox reaction occurs, associated with the elimination of the water molecule and aromatization of the dihydropiridine ring that leads to the formation of 4-(2-nitrosophenyl)pyridine analogue (Figure 2). [6,7] It has been proven that the rapid photochemical decomposition is related to the presence of the nitro group and its location in the phenyl ring. The most sensitive compounds include derivatives of the ortho-substituted analogues, i.e., nifedipine (e.g., Adalat® Bayer, Procardia® Pfizer) and nisoldipine (e.g., Sular® Shionogi).…”

“…However, this process occurs and leads to the formation of biologically inactive derivatives of halogeno-pyridine. [6,7] Nuclear magnetic resonance (NMR) spectroscopy in solution is one of the most important analytical techniques in pharmaceutical research. [8] It enables qualitative and quantitative determination of an active pharmaceutical ingredient (API), also in mixtures and biological samples.…”

Polybenzimidazole-Triphenylphosphene-Catalyzed One-Pot Synthesis and Evaluation of Dihydropyridine Derivative as Antibiotics and Antifungals

“…The studies of antimicrobial activity of the pyridine derivatives which are easily oxidized were found to be cumbersome . FDA approved the usage of DHP derivatives as antimicrobial agents, antioxidant antihypertensive, anti‐inflammatory, anticoagulant, anti‐diabetic, bronchodilator, hepatoprotective, calcium channel blocker, HIV protease inhibition, cardiovascular, analgesic, antitumor, antithrombotic, and anticonvulsant . Some of the commercial available DHP based drugs are felodipine, amlodipine, and nimodipine.…”