Selected article for: "characteristic diffraction and Methocel pre dissolved HPMC presence"
Author: Salas-Zúñiga, Reynaldo; Rodríguez-Ruiz, Christian; Höpfl, Herbert; Morales-Rojas, Hugo; Sánchez-Guadarrama, Obdulia; Rodríguez-Cuamatzi, Patricia; Herrera-Ruiz, Dea
Title: Dissolution Advantage of Nitazoxanide Cocrystals in the Presence of Cellulosic Polymers
  • Document date: 2019_12_25
    • ID: 034w5afv_30
    Snippet: Powder dissolution profiles of pure NTZ and the NTZ-GLU/NTZ-SUC cocrystals were measured in pH 7.5 phosphate buffer solution in the absence and presence of pre-dissolved polymer (0.5%, w/v; 5 mg/mL). The corresponding graphs are shown in Figure 2 . In the absence of polymer, there is no statistically significant difference (p > 0.05) between the profile of NTZ and those obtained for the cocrystals (Figure 2a) , maintaining on average a saturated .....
    Document: Powder dissolution profiles of pure NTZ and the NTZ-GLU/NTZ-SUC cocrystals were measured in pH 7.5 phosphate buffer solution in the absence and presence of pre-dissolved polymer (0.5%, w/v; 5 mg/mL). The corresponding graphs are shown in Figure 2 . In the absence of polymer, there is no statistically significant difference (p > 0.05) between the profile of NTZ and those obtained for the cocrystals (Figure 2a) , maintaining on average a saturated NTZ concentration of 0.5 mg/mL. On the contrary, in the presence of pre-dissolved HPMC and Methocel ® 60 HG, the NTZ dissolution profiles of the pure form and the cocrystals are significantly different (p < 0.05) (Figure 2b ,c). Thus, starting from the cocrystals, pre-dissolved HPMC and Methocel ® 60 HG enable the generation of transient drug concentrations (approximately 2 mg/mL) that are 4 times above NTZ solubility, following a spring-parachute profile as postulated by Guzman et al. [48] . This supersaturation state is sustained for approximately 30 min, for both cocrystals. The decay of the NTZ concentration is attributed to precipitation of pure NTZ, as indicated by PXRD analyses of the solid residues recovered after the dissolution experiments with NTZ-GLU and NTZ-SUC, that showed characteristic diffraction peaks of pure NTZ (Figures 3-5) . Overall, this analysis shows that indeed NTZ-GLU and NTZ-SUC have superior dissolution properties compared to the parent drug, suggesting that dissolution kinetics of the cocrystalline phases is extremely rapid, supersaturating the solution and precipitating in a short time period (~1-5 min), which is in agreement with our previous studies on the solution-phase stability of NTZ-GLU and NTZ-SUC in PBS pH 7.5 [8] . However, in the presence of pre-dissolved HPMC and Methocel ® 60 HG, the precipitation of pure NTZ is delayed by a time interval long enough to envision a potential improvement of the bioavailability (~30 min, see Discussion section).

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