Improving the Solid-State Photostability of Furosemide by Its Cocrystal Formation

Abstract

The photostability of three types of furosemide (FUR) cocrystal (FUR-caffeine, FUR-urea, and FURnicotinamide cocrystals) was studied under irradiation with a D65 fluorescent lamp. The coloration of the FUR-urea pellets was significantly faster than that of the intact FUR, whereas the coloration of FUR-nicotinamide was suppressed compared with that of intact FUR and the other cocrystals. In the case of FUR-urea, the chemical degradation of FUR increased by approximately 6.6% after irradiation for 90 d. On the other hand, FUR-nicotinamide showed better chemical stability, with only 1.3% of FUR degraded, which was significantly lower than the other cocrystals. The FUR-urea pellets showed a UV-Visible absorption spectrum similar to that of intact FUR, while the absorption range of FUR-nicotinamide shifted to a shorter wavelength. The light sensitivity of FUR-nicotinamide was improved because of the much lower emission of the D65 fluorescent lamp in the absorption range of the cocrystal.

Pharmaceutical cocrystals: A review of preparations, physicochemical properties and applications

“… API Coformer Ref. Furosemide Caffeine Nicotinamide 115 Brexpiprazole Catechol 108 Nifedipine Isonicotinamide 116 Progesterone Phloroglucinol 85 Antiprotozoal tinidazole p -Aminobenzoic acid 117 Salicylic acid 117 Levofloxacin Metacetamol 95 Epalrestat Betaine 104 Linagliptin Ferulic acid 118 Vitamin K3 1-Hydroxy-2-naphthoic acid 114 6-Hydroxy-2-naphthoic acid 114 Sulfamerazine 114 Tranilast Urea 119 Nicotinamide 119 Nitrofurantoin 4-Hydroxybenzoic acid 120 Vitamin D3 Vitamin D2 106

Figure 11 Diagram of the mechanisms by which cocrystals improve the chemical stability of APIs.

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Novel Drug–Drug Multicomponent Crystals of Epalrestat–Metformin: Improved Solubility and Photostability of Epalrestat and Reduced Hygroscopicity of Metformin

“…Solid-state EP is stable in the dark, and it undergoes E, Z to Z, Z isomerization when exposed to sunlight (even ambient) . From the viewpoint of crystal engineering, multicomponent crystals may provide a possibility to overcome this problem since multicomponent crystals form strong (charge-assisted) hydrogen bonds, ,− which might constrain the EP molecule in the crystal lattice and thereby slow down the E, Z to Z, Z isomerization compared to that in the pure EP.…”

“…According to Table , the order of the number of hydrogen bonds in the EP–MET crystal forms is EP–MET S ACE > EP–MET S ETOH‑H 2 O > EP–MET MH; meanwhile, the bond length of EP–MET S ACE is shorter, and the bond angle is closer to 180°, but the lengths of EP–MET MH and EP–MET S ETOH‑H 2 O are longer, and the bond angles are less than 180°, meaning that they are the strongest intermolecular interactions in the EP–MET S ACE among our multicomponent crystals, which is the reason that EP–MET S ACE have better performance in restricting photoisomerization and successfully stabilizing the conformation of EP molecules. Besides, the strong intermolecular interaction may cause a change of absorption wavelength range of the substance, so the solid-state UV experiment was carried out from 190 to 900 nm of EP and EP–MET crystal forms, as shown in Figure . Solid-state exhibits absorption over a broader range compared with EP–MET crystal forms, and EP–MET S ACE shows the smallest range among the EP–MET crystal forms.…”

Pharmaceutical Cocrystals: Molecules, Crystals, Formulations, Medicines

“…Moreover, that cocrystalline system exhibited substantial stability to temperature and humidity as shown by differential thermal analysis (DTA) and differential scanning calorimetry (DSC) results (Figure ) for a descent time interval of over a period of 13 weeks (Table ). After this study, a number of cocrystals were designed to tackle photodegradation of the APIs and nutraceutical materials. − …”