###### Abstract  
A series of different-colored glasses were tested to evaluate their ability to protect dihydropyridine antihypertensives in solution from light. The work aims to define a primary packaging capable of guaranteeing photoprotection for this class of drugs in liquid formulations as an alternative to the current formulations, which are dispensed almost exclusively in solid form. The photostability tests were performed according to international rules by exposing 11 dihydropyridine drugs in ethanol and PEG-ethanol solution to stressing light, shielded by quartz, transparent, amber, or red glass. The transparent glass proved to be completely ineffective, recording a dramatic degradation of all compounds, some of which by 10% in less than 1 min, and with complete disappearance in just 1 h. The amber glass showed a valid photoprotection for almost all compounds, apart from nifedipine and insoldipine, which degraded by 10% in less than 20 min. The adoption of red glass in filtering the light led to a satisfactory photoprotection for these two drugs, detecting concentrations above 90% for all drugs after 1 h under forced light. The results obtained can help to define safe dispensing systems of liquid formulations of dihydropyridine drugs, which are necessary for those patients who cannot take tablets. dihydropyridine drugs; photoprotection; stressing test; glass containers; multivariate curve resolution +
Footnote †: journal: Medical  
products and minimize their degradation [1; 2; 8; 9; 10]. Most of these studies focus on defining new formulations that can protect drugs from light [11; 12; 13]. Dihhydropyridine drugs (DHPs) are an important class of antihypertensives that interact on the L-type calcium channels of the smooth muscle of the arterioles, where they counteract the entry of calcium, prolonging the duration of the action potential and thus reducing vasoconstriction [14; 15]. Unfortunately, DHPs are particularly sensitive to light, and many papers deal with this topic. The photodegradation process mainly involves the oxidation of the dihydropyridine ring to pyridine, and only for some DHPs have secondary photoproducts been detected [16; 17]. The oxidation of the molecule causes the total loss of pharmacological activity with the simultaneous production of singlet oxygen and superoxide species, potential inducers of phototoxic reactions [7]. Due to the rapid photodegradation kinetics in solution, DHPs are formulated almost exclusively in solid form, especially tablets. Currently on the market, only inmodipine (NM) and nifedipine (NF) are also formulated as hydroalcoholic solutions in amber glass containers. The bottle containing NF is in turn covered by a black plastic film, which certainly increases the degree of protection, but unfortunately prevents viewing of the content. The use of liquid formulations may be necessary in cases of difficulty in swallowing tablets. 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 cyclodext, 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. In the present work, the stability in hydroalcoholic solution of 11 DHPs, all currently used in antihypertensive therapy, was tested under transparent, amber, and red glass. The stability test was also carried out using a quartz container as a reference, as this material is known to be transparent at all wavelengths. The following DHPs were involved in this study: amlodipine (AM), clinidipine (CL), felodipine (FL), isradipine (IS), lacidipine (LC), manidipine (MN), nicardipine (NC), nifedipine (NF), immodipine (NM), nisoldipine (NS), and nitrendipine (NT).