Abstract:
PURPOSE:An asymmetric membrane (AM) tablet was developed for a soluble model compound to study the in vitro drug release mechanisms in challenge conditions, including osmotic gradients, concentration gradients, and under potential coating failure modes. Porous, semipermable membrane integrity may be compromised by a high fat meal or by the presence of a defect in the coating that could cause a safety concern about dose-dumping. METHODS:The osmotic and diffusional release mechanisms of the AM tablet were independently shut down such that their individual contribution to the overall drug release was measured. Shut off of osmotic and diffusional release was accomplished by performing dissolution studies into receptor solutions with osmotic pressure above the internal core osmotic pressure and into receptor solutions saturated with drug, respectively. The effect of coating failure modes on in vitro drug release from the AM tablet was assessed through a simulated high-fat meal and by intentionally compromising the coating integrity. RESULTS:The predominant drug release mechanism for the AM tablet was osmotic and accounted for approximately 90-95% of the total release. Osmotic release was shutoff when the receptor media osmotic pressure exceeded 76 atm. Diffusional release of the soluble drug amounted to 5-10% of the total release mechanism. The observed negative in vitro food effect was attributed to the increased osmotic pressure from the high fat meal when compared to the predicted release rates in sucrose media with the same osmotic pressure. This suppression in drug release rate due to a high fat meal is not anticipated to affect in vivo performance of the dosage form, as the rise in pressure is short-lived. CONCLUSIONS:Drug release from the AM system studied was determined to be robust to varying and extreme challenge conditions. The conditions investigated included varying pH, agitation rate, media osmotic pressure, media saturated with drug to eliminate the concentration gradient, simulated high fat meal, and intentionally placed film coating defects. Osmotic and diffusional shut off experiments suggest that the mechanism governing drug release is a combination of osmotic and diffusional at approximately 90-95% and 5-10%, respectively. In addition, the coating failure mode studies revealed this formulation and design is not significantly affected by a high fat meal or by an intentionally placed defect in the film coating, and more specifically, did not result in a burst of drug release.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Am Ende MT,Miller LAdoi
10.1007/s11095-006-9142-ysubject
Has Abstractpub_date
2007-02-01 00:00:00pages
288-97issue
2eissn
0724-8741issn
1573-904Xjournal_volume
24pub_type
杂志文章abstract:PURPOSE:In vitro and in vivo permeation studies were conducted to evaluate the characteristic of percutaneous administration of high hydrophilic drug L-carnitine (LC) by Functional MicroArray (FMA) painless intradermal delivery system. METHODS:In vitro study was designed to assess the effects of various skins, donor c...
journal_title:Pharmaceutical research
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journal_title:Pharmaceutical research
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journal_title:Pharmaceutical research
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pub_type: 杂志文章
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更新日期:2003-03-01 00:00:00
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journal_title:Pharmaceutical research
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更新日期:1999-02-01 00:00:00
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journal_title:Pharmaceutical research
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更新日期:2016-06-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章,评审
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更新日期:1990-01-01 00:00:00
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更新日期:2014-01-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
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journal_title:Pharmaceutical research
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更新日期:2004-05-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
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更新日期:2010-02-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
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更新日期:2003-12-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
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更新日期:2003-08-01 00:00:00