Rational design, supramolecular synthesis and solid state characterization of two bicomponent solid forms of mebendazole

Abstract

Two novel bicomponent solid forms of mebendazole (MBZ), were developed as a mean to modulate its psychochemical and pharmaceutical properties. Supramolecular synthesis of MBZ A or C with perchloric or...

Pharmaceutical Salts of Fenbendazole with Organic Counterions: Structural Analysis and Solubility Performance

“…In this case, however, a proton transfer from O2 of the TSA to N1 of the FNB imidazole ring was seen to occur, indicating a possible tautomerism of FNB in solution. 67,72 The water molecule accepted the N−H•••O hydrogen bond from N2 of the imidazole group, disrupting the H-bonded chain structure seen in [FNB+TSA] (1:1) (Figure 5a). In addition, the H 2 O molecule acted as a hydrogen-bond donor for the sulfonate oxygens, connecting the TSA anions to form a distinct chain along the b axis with the C(4) graph set notation (Figure S8a).…”

“…Since the crystal structure of the parent FNB remains unknown, a detailed assignment of the drug IR and/or Raman spectra is not straightforward because of the tautomeric equilibrium, which is expected to exist in the compounds carrying the benzimidazole carbamate moiety . However, previous investigations on structurally related benzimidazole antihelmintic agents (albendazole, , mebendazole, − and flubendazole) enabled a tentative assignment of the bands associated with the main chemical groups of FNB and identification of the structural changes related to the formation of new multicomponent crystals. As Figure illustrates, the intense band at 3338 cm –1 was assigned to the N–H stretching mode of the carbamate moiety, while the broad band centered at ∼2650 cm –1 most likely corresponded to the a ν­(N–H) stretch of the benzimidazole ring, in accord with the literature data. , The carbamate carbonyl stretching vibrations (CO) appeared at 1708 cm –1 , and the N–H bending and the C–N stretching modes are expected for a relatively broad band centered at 1630 cm –1 .…”

“…3.1 and 3.7 times more soluble than form C of the drug in 0.1 M HCl solution at 37 °C after 780 min of a dissolution experiment . Under similar conditions, nitrate and perchlorate salts of mebendazole showed apparent solubility improvements by factors of 1.2 and 1.7, respectively, in comparison to polymorph C of the parent drug. , In the case of albendazole hydrochloride, a slightly higher advantage (∼4–9 times) in the apparent solubility has been observed under SGF (pH 1.2) conditions at 37.0 °C . As was mentioned above, the value of an apparent solubility is both system and condition specific, so that, in contrast to thermodynamic solubility, it can vary in a wide range, depending on the experimental setup and dissolution environment.…”

Structural features, dissolution performance and anthelmintic efficacy of multicomponent solid forms of fenbendazole with maleic and oxalic acids

“…FT-IR spectroscopy further supported the formation of novel multicomponent crystals made up of FNB and carboxylic acids. Based on prior research on structurally similar benzimidazole anthelmintic drugs (albendazole, 59,60 mebendazole, 61–63 and flubendazole 64 ), tentative assignment of the bands associated with the primary chemical groups of FNB and identification of structural modifications induced by the alteration of the crystalline environment were carried out. As Fig.…”

“…Similar spectral features were also observed for the previously reported FNB salts with methanesulfonic and p -toluenesulfonic acids 30 as well as flubendazole maleate 64 and other known salts of benzimidazole-based drugs. 59–63 According to the literature data, 60,61 the appearance of a new weak vibration band at 1583 cm −1 for [FNB + Mal] (1 : 1) and 1565 cm −1 for [FNB + Ox] (1 : 1) may be attributed to the partial loss of the double bond character by the C–N bond in the benzimidazole ring due to the nitrogen atom protonation, though confident band assignment in this region is not a straightforward task. While spectroscopic analysis indicates that the carbamate and benzimidazole groups of FNB are involved in intermolecular interactions with the corresponding acids in the studied multicomponent forms, the nature of the obtained adducts (cocrystal or salt) cannot be unambiguously determined based solely on FT-IR data.…”