Comparative Pharmaceutical Evaluation of Candesartan and Candesartan Cilexetil: Physicochemical Properties, In Vitro Dissolution and Ex Vivo In Vivo Studies was written by Amer, Ahmed M.;Allam, Ahmed N.;Abdallah, Ossama Y.. And the article was included in AAPS PharmSciTech in 2018.Computed Properties of C33H34N6O6 This article mentions the following:
The aim of the present work is to answer the question is it possible to replace the ester prodrug candesartan cilexetil (CC) by its active metabolite candesartan (C) to bypass the in vivo variable effect of esterase enzymes. A comparative physicochem. evaluation was conducted through solubility, dissolution, and stability studies; addnl., ex vivo permeation and in vivo studies were assessed. C demonstrated higher solubility over CC at alk. pH. Moreover, dissolution testing using the pharmacopeial method showed better release profile of C even in the absence of surfactant in the testing medium. Both drugs demonstrated a slight degradation in acidic pH after short-term stability. Instead, shifting to alk. pH of 6.5 and 7.4 showed superiority of C solution stability compared to CC solution The ex vivo permeation results demonstrated that the parent compound C has a significant (P < 0.05) enhanced permeation compared to its prodrug from CC, that agreed with in vivo results in which C suspension reached significantly (P < 0.05) higher Cmax of 1.39 ± 0.59μg/mL at Tmax of 0.66 ± 0.11 h, while CC suspension reached Cmax of 0.47 ± 0.22μg/mL at Tmax of 2.00 ± 0.27 h, a lag period of 40 min is needed prior to detection of any absorbed CC in plasma. Those findings are not in agreement with the previously reported rationale on the prodrug formation owing to the poor permeability of the parent compound, suggesting the possibility of marketing the parent drug candesartan for clin. use similarly to azilsartan and its prodrug. In the experiment, the researchers used many compounds, for example, 1-(((Cyclohexyloxy)carbonyl)oxy)ethyl 1-((2′-(2H-tetrazol-5-yl)-[1,1′-biphenyl]-4-yl)methyl)-2-ethoxy-1H-benzo[d]imidazole-7-carboxylate (cas: 145040-37-5Computed Properties of C33H34N6O6).
1-(((Cyclohexyloxy)carbonyl)oxy)ethyl 1-((2′-(2H-tetrazol-5-yl)-[1,1′-biphenyl]-4-yl)methyl)-2-ethoxy-1H-benzo[d]imidazole-7-carboxylate (cas: 145040-37-5) belongs to imidazole derivatives. Imidazole derivatives generally have good solubility in protic solvents. Simple imidazole derivatives, such as 1H-imidazole, 2-methyl-1H-imidazole, and 1,2-dimethylimidazole, have very high solubility in water. Imidazole has been usedin the lysis, wash and elution buffer for the purification of histidine tagged Sonic Hedgehog(shh-N) protein, in elution buffer in stepwise gradient for the purification of histidine tagged aldo keto reductases using nickel affinity chromatography, as a component of homogenization buffer for the purification of phagosomal compartments from dendritic cells.Computed Properties of C33H34N6O6
Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem