PMC:7561592 / 13795-17058 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":"In Vitro Dissolution Studies\nDissolution studies were performed with a mini-paddle apparatus (Agilent Technologies 708-DS apparatus configured with TruAlign 200-mL vessels and electropolished stainless steel mini-paddles; Agilent, USA). Experiments were conducted in a two-stage approach: in SGFsp pH 1.2 (total volume with sample: 100 mL), for 1 h, followed by SIFsp pH 6.8 (final volume: 200 mL), for 3 h. A dissolution study with a sequential media change mimics the passage of oral dosage forms through the GI tract, providing an understanding of the in vivo drug performance (28). Experiments were conducted at 37 ± 0.5°C and the agitation rate of the mini-paddle was set to 50 revolutions per minute (rpm). Sample collection took place at 5, 15, 30, 45, 60, 75, 90, 120, 180 and 240 min. Two-millilitre samples were withdrawn (with volume replacement with the corresponding media), using a 2-mL glass syringe (Fortuna Optima® fitted with a stainless tubing) through a cannula fitted with a full flow filter (10 μm). All experiments were performed without direct light exposure to avoid photodegradation of the drugs (29,30). After collection, samples were filtered through a GF/D (2.7 μm) filter and treated. Sample treatment was as follows: 1000 μL of acetonitrile (montelukast) or 10% (v/v) TFA/water (mesalazine) were added to 500 μL of sample. This mixture was vortexed (HTZ, UK) for 1 min and centrifuged (8000 rpm, 15 min, 4°C) (Beckman Coulter J2-MC centrifuge, UK). The supernatant was filtered through a RC (montelukast) or PTFE (mesalazine) (0.45 μm) filter, placed in an HPLC amber vial and analysed. The pH of the media was measured at the end of each experiment.\nThe effect of different administration scenarios and testing conditions was investigated by varying the dissolution test parameters, as described in Table II. These were as follows: (1) effect of co-administration of formulation with selected vehicles in comparison to direct administration of formulation; (2) effect of different mixing patterns (i.e. time between preparation and administration/testing of the formulation-vehicle mixture); and (3) effect of hydrodynamics (50 vs 100 rpm, in selected studies of Pentasa® and Singulair® granules).\nTable II Dosing Scenarios and Testing Conditions Investigated\nSetup Agitation speed (rpm) Scenario: direct introduction Scenario: mixing with vehicles Formulations Mixing pattern (h)\n1 50 ✓ M, OJ, BLS, PY, APSUK, F, OS, GY, APSDE All 0\n2 50 N/A M, OJ, BLS, PY, APSUK All 4\n3 100 ✓ M, OJ, BLS, PY, APSUK Singulair®, Pentasa® 0\nBLS, blackcurrant squash; OS, orange squash; M, milk; F, formula; OJ, orange juice; PY, plain yoghurt; GY, Greek yoghurt; APSUK, applesauce UK; APSDE, applesauce DE; N/A, not applicable\nAll experiments were performed in triplicate. Fresh calibration curves (concentration range: 0.5–100 μg/mL (montelukast) and 0.5–200 μg/mL (mesalazine)) were prepared in the corresponding media, by appropriate dilution of a 1000 μg/mL stock solution of the analytical standard in methanol (montelukast) or 0.05% TFA/water (mesalazine); the same treatment process was applied as described for the samples. Results were expressed as mean percentage of drug dissolved ± standard deviation (S.D.), at the given sampling time.","divisions":[{"label":"title","span":{"begin":0,"end":28}},{"label":"p","span":{"begin":29,"end":1681}},{"label":"p","span":{"begin":1682,"end":2741}},{"label":"table-wrap","span":{"begin":2230,"end":2741}},{"label":"label","span":{"begin":2230,"end":2238}},{"label":"caption","span":{"begin":2239,"end":2291}},{"label":"p","span":{"begin":2239,"end":2291}},{"label":"table","span":{"begin":2292,"end":2555}},{"label":"tr","span":{"begin":2292,"end":2412}},{"label":"th","span":{"begin":2292,"end":2297}},{"label":"th","span":{"begin":2298,"end":2319}},{"label":"th","span":{"begin":2320,"end":2349}},{"label":"th","span":{"begin":2350,"end":2380}},{"label":"th","span":{"begin":2381,"end":2393}},{"label":"th","span":{"begin":2394,"end":2412}},{"label":"tr","span":{"begin":2413,"end":2465}},{"label":"td","span":{"begin":2413,"end":2414}},{"label":"td","span":{"begin":2415,"end":2417}},{"label":"td","span":{"begin":2418,"end":2419}},{"label":"td","span":{"begin":2420,"end":2459}},{"label":"td","span":{"begin":2460,"end":2463}},{"label":"td","span":{"begin":2464,"end":2465}},{"label":"tr","span":{"begin":2466,"end":2502}},{"label":"td","span":{"begin":2466,"end":2467}},{"label":"td","span":{"begin":2468,"end":2470}},{"label":"td","span":{"begin":2471,"end":2474}},{"label":"td","span":{"begin":2475,"end":2496}},{"label":"td","span":{"begin":2497,"end":2500}},{"label":"td","span":{"begin":2501,"end":2502}},{"label":"tr","span":{"begin":2503,"end":2555}},{"label":"td","span":{"begin":2503,"end":2504}},{"label":"td","span":{"begin":2505,"end":2508}},{"label":"td","span":{"begin":2509,"end":2510}},{"label":"td","span":{"begin":2511,"end":2532}},{"label":"td","span":{"begin":2533,"end":2553}},{"label":"td","span":{"begin":2554,"end":2555}},{"label":"table-wrap-foot","span":{"begin":2556,"end":2741}},{"label":"p","span":{"begin":2556,"end":2741}}],"tracks":[{"project":"2_test","denotations":[{"id":"33063245-29380369-28136","span":{"begin":581,"end":583},"obj":"29380369"},{"id":"33063245-15497676-28137","span":{"begin":1126,"end":1128},"obj":"15497676"}],"attributes":[{"subj":"33063245-29380369-28136","pred":"source","obj":"2_test"},{"subj":"33063245-15497676-28137","pred":"source","obj":"2_test"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"2_test","color":"#97ec93","default":true}]}]}}