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

Abstract

The stability profile of a new 1,4-dihydropyridine derivative (DHP), representative of a series with a hexahydroquinoline ring, was studied to design light-stable liquid formulations. This molecule, named M3, has been shown among the analogs to have a high capacity to block both L- and T-type calcium channels. The ethanol solution of the drug was subjected to a photodegradation test, in accordance with standard rules. The concentrations of the drug and its byproducts were estimated using multivariate curve resolution, applied to the spectral data collected during the test. The improvement of both the photostability and water solubility of M3 was investigated by adding the surfactant polysorbate 20 in a 1:5 ratio to aqueous solutions of the drug. These formulations were exposed to stressing light in containers of bleu polyethylene terephthalate (PET), amber PET, and covered amber PET. The best results were obtained when using the covered amber PET container, reaching a degradation percentage of the drug less than 5% after 12 h under an irradiance power of 450 W/m2. The stability of the compound was compared to that of nimodipine (NIM) under the same conditions.

Use of Pluronic Surfactants in Gel Formulations of Photosensitive 1,4-Dihydropyridine Derivatives: A Potential Approach in the Treatment of Neuropathic Pain

“…The adoption of dark glass containers is the most used method to protect the few available liquid formulations of DHPs today. Alternatively, matrices based on cyclodextrins, liposomes, niosomes or non-ionic surfactants have been studied as photostabilization systems [ 10 , 11 , 12 ]. Over the past decade, many efforts have been devoted to the development of drug delivery systems based on the use of nanoscale materials, including polymer micelles and polymer–drug conjugates, in which the drugs can simply be entrapped or covalently bound [ 13 , 14 , 15 , 16 , 17 ].…”

Gel Formulation of Nabumetone and a Newly Synthesized Analog: Microemulsion as a Photoprotective Topical Delivery System

“…Oral treatment with NSAIDs has been in fact associated with increased gastrointestinal (GI), renal, and Furthermore, when the pharmacokinetics of a drug is not favorable and at the same time the absorption through the skin is slow, a system to protect the drugs from prolonged sun exposure after application should be designed. Some examples are proposed in the studies of incorporation into supramolecular systems, such as cyclodextrins, liposomes, and niosomes, often supported by the addition of antioxidants and solar filters [12][13][14][15][16][17]. Recent investigations suggest the use of microemulsions (ME) as dispersion systems to realize photoprotective carriers for drugs [18][19][20].…”

Synthesis, Docking and Antihypertensive Activity of Pyridone Derivatives

“…[4b] Dihydropyridine derivatives (DHPD) antihypertensive activity may be attributed to their role as calcium channel blockers. [16] From the previous literature, Dihydripyridone derivatives were exhibited the most potent calcium antagonists and lowered rat blood pressure significantly in comparison with DMSO as control, and nifedipine was used as a positive control. [17] Our work represents practical and theoretical studies on the antihpotensive effect after inserting the sulfonamide derivatives on the dihydropyridine moiety.…”