PMC:7561592 / 35836-39057 JSONTXT

{"target":"http://pubannotation.org/docs/sourcedb/PMC/sourceid/7561592","sourcedb":"PMC","sourceid":"7561592","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7561592","text":"Assessing the Impact of In Vitro Hydrodynamics\nIn vitro drug dissolution from the formulations tested (montelukast: Singulair® granules; mesalazine: Pentasa® granules) was influenced by the hydrodynamic conditions, for all the scenarios tested (Figs. 8 and 9).\nFig. 8 Mean percentage of drug dissolved (± S.D.) of montelukast from Singulair® granules (top panel) and mesalazine from Pentasa® granules (bottom panel), after testing under two agitation rate conditions: 50 rpm (dashed bars) and 100 rpm (full bars). Dotted vertical lines represent the time of medium change\nFig. 9 Effect of dissolution hydrodynamics on AUC0–4 h of Singulair® (montelukast) and Pentasa® (mesalazine) granules. Asterisk symbol denotes a statistical difference in AUC0–4 h between drug dissolution when agitation rate was set at 50 (dashed bars) and 100 rpm (full bars)\nFor Singulair® granules, higher agitation conditions resulted in a higher percentage of drug dissolved (4 h) when the formulation was mixed with milk, orange juice, applesauce and plain yoghurt (increase in percentage of drug dissolved (4 h) = 16.1, 27.5, 1.4 and 8.6%, respectively). A significantly higher AUC0–4h was observed when the granules were mixed with these vehicles and tested at 100 rpm, in comparison with 50 rpm (Fig. 9). This is probably related to the effect of the increased hydrodynamics, which result in a better dispersion of the drug product-vehicle mixture and, consequently, facilitate drug dissolution from the vehicles (35). Dissolution testing of the granules mixed with blackcurrant squash at high agitation rate (100 rpm) resulted in a significantly lower AUC0–4h in comparison with the dissolution testing at low agitation rate (50 rpm.) For the scenario of direct administration, drug dissolution was likely limited by the drug solubility in the media and not significantly affected by the increase in agitation rate (11).\nTesting at 100 rpm also resulted in a higher drug dissolution and significantly higher AUC0–4h, when the Pentasa® granules were mixed with milk, orange juice, plain yoghurt and applesauce, compared with 50 rpm (p \u003c 0.05).\nIn comparison with the results obtained when testing at 50 rpm, increasing the agitation rate to 100 rpm resulted in a reduced discrimination between drug dissolution profiles. Nevertheless, comparison of AUC0–4h of the dissolution profiles obtained at 100 rpm still revealed significant differences between direct introduction of the formulation and mixing with vehicles (p \u003c 0.05). Therefore, the differences in drug dissolution for co-administration with vehicles in comparison with direct administration of formulation were not due to the agitation speed set (50 rpm) since they were still observed when testing at a higher agitation rate.\nThe turbulent flow regime generated by USP II apparatus dissolution setups would not represent the relatively nonturbulent in vivo conditions (24,36,37). Therefore, differences observed in drug dissolution behaviour in vitro might not be observed in vivo in cases where peristalsis and contact with the lumen play a role. For example, meal viscosity has resulted in a slower tablet disintegration for BCS class III drugs co-administered with food (38).","divisions":[{"label":"title","span":{"begin":0,"end":46}},{"label":"p","span":{"begin":47,"end":848}},{"label":"figure","span":{"begin":261,"end":571}},{"label":"label","span":{"begin":261,"end":267}},{"label":"caption","span":{"begin":268,"end":571}},{"label":"p","span":{"begin":268,"end":571}},{"label":"figure","span":{"begin":572,"end":848}},{"label":"label","span":{"begin":572,"end":578}},{"label":"caption","span":{"begin":579,"end":848}},{"label":"p","span":{"begin":579,"end":848}},{"label":"p","span":{"begin":849,"end":1902}},{"label":"p","span":{"begin":1903,"end":2124}},{"label":"p","span":{"begin":2125,"end":2768}}],"tracks":[{"project":"2_test","denotations":[{"id":"33063245-19034672-28147","span":{"begin":1495,"end":1497},"obj":"19034672"},{"id":"33063245-32592045-28148","span":{"begin":1898,"end":1900},"obj":"32592045"},{"id":"33063245-23988843-28149","span":{"begin":2912,"end":2914},"obj":"23988843"},{"id":"33063245-29608886-28150","span":{"begin":2915,"end":2917},"obj":"29608886"},{"id":"33063245-15725550-28151","span":{"begin":2918,"end":2920},"obj":"15725550"},{"id":"33063245-22782559-28152","span":{"begin":3217,"end":3219},"obj":"22782559"}],"attributes":[{"subj":"33063245-19034672-28147","pred":"source","obj":"2_test"},{"subj":"33063245-32592045-28148","pred":"source","obj":"2_test"},{"subj":"33063245-23988843-28149","pred":"source","obj":"2_test"},{"subj":"33063245-29608886-28150","pred":"source","obj":"2_test"},{"subj":"33063245-15725550-28151","pred":"source","obj":"2_test"},{"subj":"33063245-22782559-28152","pred":"source","obj":"2_test"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"2_test","color":"#ec93bc","default":true}]}]}}