Amorphous solid dispersion enhances permeation of poorly soluble ABT-102: true supersaturation vs. apparent solubility enhancement
Amorphous solid dispersions (ASDs) represent a promising formulation approach for poorly soluble drugs. We explored the formulation-related impact of ASDs on permeation rate, apparent solubility and molecular solubility of the poorly soluble drug ABT-102. The influence of fasted state simulated inte...
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| Main Authors: | , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
20 August 2012
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| In: |
International journal of pharmaceutics
Year: 2012, Volume: 437, Issue: 1, Pages: 288-293 |
| ISSN: | 1873-3476 |
| DOI: | 10.1016/j.ijpharm.2012.08.014 |
| Online Access: | Verlag, Volltext: http://dx.doi.org/10.1016/j.ijpharm.2012.08.014 Verlag, Volltext: http://www.sciencedirect.com/science/article/pii/S0378517312008095 
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| Author Notes: | Kerstin J. Frank, Karin M. Rosenblatt, Ulrich Westedt, Peter Hölig, Jörg Rosenberg, Markus Mägerlein, Gert Fricker, Martin Brandl |
| Summary: | Amorphous solid dispersions (ASDs) represent a promising formulation approach for poorly soluble drugs. We explored the formulation-related impact of ASDs on permeation rate, apparent solubility and molecular solubility of the poorly soluble drug ABT-102. The influence of fasted state simulated intestinal fluid (FaSSIF) as dispersion medium was also studied. ASDs were prepared by hot-melt extrusion. Permeation rate was assessed by the Caco-2 transwell assay. Cell viability and barrier integrity were assured by AlamarBlue©, TEER and permeability of the hydrophilic marker carboxyfluorescein. Apparent solubility and molecular solubility were evaluated by using centrifugation and inverse dialysis, respectively. The in vitro permeation rate of ABT-102 from aqueous dispersions of the ASD was found 4 times faster than that from the dispersions of the crystals, while apparent solubility and molecular solubility of ABT-102 were increased. Yet, a further increase in apparent solubility due to micellar solubilization as observed when dispersing the ASD in FaSSIF, did not affect molecular solubility or permeation rate. Overall, a good correlation between permeation rate and molecular solubility but not apparent solubility was seen. |
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| Item Description: | Gesehen am 23.04.2018 |
| Physical Description: | Online Resource |
| ISSN: | 1873-3476 |
| DOI: | 10.1016/j.ijpharm.2012.08.014 |