Oral saquinavir mesylate solid dispersions: In vitro dissolution, Caco-2 cell model permeability and in vivo absorption studies
The aim of this study was to investigate the effects of solid dispersions (SDs) containing a mixture of PVP K30 and different carriers (PEG 4000 or Gelucire® 44/14) on in vitro dissolution and intestinal permeability of saquinavir mesylate (SQVM), and to evaluate their impact on the oral bioavailabi...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Caon, Thiago [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2015transfer abstract |
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| Umfang: |
7 |
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| Übergeordnetes Werk: |
Enthalten in: Role of sulfur in combating arsenic stress through upregulation of important proteins, and - Amna, Syeda ELSEVIER, 2020, an international journal on the science and technology of wet and dry particulate systems, Amsterdam [u.a.] |
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| Übergeordnetes Werk: |
volume:269 ; year:2015 ; pages:200-206 ; extent:7 |
| Links: |
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| DOI / URN: |
10.1016/j.powtec.2014.09.012 |
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| 520 | |a The aim of this study was to investigate the effects of solid dispersions (SDs) containing a mixture of PVP K30 and different carriers (PEG 4000 or Gelucire® 44/14) on in vitro dissolution and intestinal permeability of saquinavir mesylate (SQVM), and to evaluate their impact on the oral bioavailability of SQVM in a dog model by comparing with Svir® (commercial formulation). Although hydrophilic carriers such as PEG may provide advantages in terms of drug release, their limited solubilization capacity led to precipitation of drug and therefore to a reduced and variable oral bioavailability, as observed for SQVM from this carrier. On the other hand, self-emulsifying systems composed of Gelucire® 44/14 or oleic acid/Castor oil mixture (Svir®) were more effective at improving oral bioavailability of SQVM (approximately 5-fold higher than PEG-based formulations), probably due to the improved solubility of SQVM in GI tract, reduced particle size and inhibitory effects on P-gp (a 2.3-fold reduction of efflux ratio). The selection of carriers and other excipients which display a solubilizing effect and inhibitory effect on P-gp seems to be key factors for increasing the oral bioavailability of SQVM. Gelucire might be considered as a promising carrier for the development of a SQVM commercial formulation. | ||
| 520 | |a The aim of this study was to investigate the effects of solid dispersions (SDs) containing a mixture of PVP K30 and different carriers (PEG 4000 or Gelucire® 44/14) on in vitro dissolution and intestinal permeability of saquinavir mesylate (SQVM), and to evaluate their impact on the oral bioavailability of SQVM in a dog model by comparing with Svir® (commercial formulation). Although hydrophilic carriers such as PEG may provide advantages in terms of drug release, their limited solubilization capacity led to precipitation of drug and therefore to a reduced and variable oral bioavailability, as observed for SQVM from this carrier. On the other hand, self-emulsifying systems composed of Gelucire® 44/14 or oleic acid/Castor oil mixture (Svir®) were more effective at improving oral bioavailability of SQVM (approximately 5-fold higher than PEG-based formulations), probably due to the improved solubility of SQVM in GI tract, reduced particle size and inhibitory effects on P-gp (a 2.3-fold reduction of efflux ratio). The selection of carriers and other excipients which display a solubilizing effect and inhibitory effect on P-gp seems to be key factors for increasing the oral bioavailability of SQVM. Gelucire might be considered as a promising carrier for the development of a SQVM commercial formulation. | ||
| 700 | 1 | |a Kratz, Jadel Muller |4 oth | |
| 700 | 1 | |a Kuminek, Gislaine |4 oth | |
| 700 | 1 | |a Heller, Melina |4 oth | |
| 700 | 1 | |a Konig, Ricardo Augusto |4 oth | |
| 700 | 1 | |a Micke, Gustavo Amadeu |4 oth | |
| 700 | 1 | |a Koester, Letícia Scherer |4 oth | |
| 700 | 1 | |a Simões, Cláudia Maria Oliveira |4 oth | |
| 773 | 0 | 8 | |i Enthalten in |n Elsevier Science |a Amna, Syeda ELSEVIER |t Role of sulfur in combating arsenic stress through upregulation of important proteins, and |d 2020 |d an international journal on the science and technology of wet and dry particulate systems |g Amsterdam [u.a.] |w (DE-627)ELV005093252 |
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10.1016/j.powtec.2014.09.012 doi GBVA2015023000024.pica (DE-627)ELV029397480 (ELSEVIER)S0032-5910(14)00800-6 DE-627 ger DE-627 rakwb eng 660 660 DE-600 630 640 580 VZ BIODIV DE-30 fid 42.00 bkl Caon, Thiago verfasserin aut Oral saquinavir mesylate solid dispersions: In vitro dissolution, Caco-2 cell model permeability and in vivo absorption studies 2015transfer abstract 7 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier The aim of this study was to investigate the effects of solid dispersions (SDs) containing a mixture of PVP K30 and different carriers (PEG 4000 or Gelucire® 44/14) on in vitro dissolution and intestinal permeability of saquinavir mesylate (SQVM), and to evaluate their impact on the oral bioavailability of SQVM in a dog model by comparing with Svir® (commercial formulation). Although hydrophilic carriers such as PEG may provide advantages in terms of drug release, their limited solubilization capacity led to precipitation of drug and therefore to a reduced and variable oral bioavailability, as observed for SQVM from this carrier. On the other hand, self-emulsifying systems composed of Gelucire® 44/14 or oleic acid/Castor oil mixture (Svir®) were more effective at improving oral bioavailability of SQVM (approximately 5-fold higher than PEG-based formulations), probably due to the improved solubility of SQVM in GI tract, reduced particle size and inhibitory effects on P-gp (a 2.3-fold reduction of efflux ratio). The selection of carriers and other excipients which display a solubilizing effect and inhibitory effect on P-gp seems to be key factors for increasing the oral bioavailability of SQVM. Gelucire might be considered as a promising carrier for the development of a SQVM commercial formulation. The aim of this study was to investigate the effects of solid dispersions (SDs) containing a mixture of PVP K30 and different carriers (PEG 4000 or Gelucire® 44/14) on in vitro dissolution and intestinal permeability of saquinavir mesylate (SQVM), and to evaluate their impact on the oral bioavailability of SQVM in a dog model by comparing with Svir® (commercial formulation). Although hydrophilic carriers such as PEG may provide advantages in terms of drug release, their limited solubilization capacity led to precipitation of drug and therefore to a reduced and variable oral bioavailability, as observed for SQVM from this carrier. On the other hand, self-emulsifying systems composed of Gelucire® 44/14 or oleic acid/Castor oil mixture (Svir®) were more effective at improving oral bioavailability of SQVM (approximately 5-fold higher than PEG-based formulations), probably due to the improved solubility of SQVM in GI tract, reduced particle size and inhibitory effects on P-gp (a 2.3-fold reduction of efflux ratio). The selection of carriers and other excipients which display a solubilizing effect and inhibitory effect on P-gp seems to be key factors for increasing the oral bioavailability of SQVM. Gelucire might be considered as a promising carrier for the development of a SQVM commercial formulation. Kratz, Jadel Muller oth Kuminek, Gislaine oth Heller, Melina oth Konig, Ricardo Augusto oth Micke, Gustavo Amadeu oth Koester, Letícia Scherer oth Simões, Cláudia Maria Oliveira oth Enthalten in Elsevier Science Amna, Syeda ELSEVIER Role of sulfur in combating arsenic stress through upregulation of important proteins, and 2020 an international journal on the science and technology of wet and dry particulate systems Amsterdam [u.a.] (DE-627)ELV005093252 volume:269 year:2015 pages:200-206 extent:7 https://doi.org/10.1016/j.powtec.2014.09.012 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U FID-BIODIV 42.00 Biologie: Allgemeines VZ AR 269 2015 200-206 7 045F 660 |
| spelling |
10.1016/j.powtec.2014.09.012 doi GBVA2015023000024.pica (DE-627)ELV029397480 (ELSEVIER)S0032-5910(14)00800-6 DE-627 ger DE-627 rakwb eng 660 660 DE-600 630 640 580 VZ BIODIV DE-30 fid 42.00 bkl Caon, Thiago verfasserin aut Oral saquinavir mesylate solid dispersions: In vitro dissolution, Caco-2 cell model permeability and in vivo absorption studies 2015transfer abstract 7 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier The aim of this study was to investigate the effects of solid dispersions (SDs) containing a mixture of PVP K30 and different carriers (PEG 4000 or Gelucire® 44/14) on in vitro dissolution and intestinal permeability of saquinavir mesylate (SQVM), and to evaluate their impact on the oral bioavailability of SQVM in a dog model by comparing with Svir® (commercial formulation). Although hydrophilic carriers such as PEG may provide advantages in terms of drug release, their limited solubilization capacity led to precipitation of drug and therefore to a reduced and variable oral bioavailability, as observed for SQVM from this carrier. On the other hand, self-emulsifying systems composed of Gelucire® 44/14 or oleic acid/Castor oil mixture (Svir®) were more effective at improving oral bioavailability of SQVM (approximately 5-fold higher than PEG-based formulations), probably due to the improved solubility of SQVM in GI tract, reduced particle size and inhibitory effects on P-gp (a 2.3-fold reduction of efflux ratio). The selection of carriers and other excipients which display a solubilizing effect and inhibitory effect on P-gp seems to be key factors for increasing the oral bioavailability of SQVM. Gelucire might be considered as a promising carrier for the development of a SQVM commercial formulation. The aim of this study was to investigate the effects of solid dispersions (SDs) containing a mixture of PVP K30 and different carriers (PEG 4000 or Gelucire® 44/14) on in vitro dissolution and intestinal permeability of saquinavir mesylate (SQVM), and to evaluate their impact on the oral bioavailability of SQVM in a dog model by comparing with Svir® (commercial formulation). Although hydrophilic carriers such as PEG may provide advantages in terms of drug release, their limited solubilization capacity led to precipitation of drug and therefore to a reduced and variable oral bioavailability, as observed for SQVM from this carrier. On the other hand, self-emulsifying systems composed of Gelucire® 44/14 or oleic acid/Castor oil mixture (Svir®) were more effective at improving oral bioavailability of SQVM (approximately 5-fold higher than PEG-based formulations), probably due to the improved solubility of SQVM in GI tract, reduced particle size and inhibitory effects on P-gp (a 2.3-fold reduction of efflux ratio). The selection of carriers and other excipients which display a solubilizing effect and inhibitory effect on P-gp seems to be key factors for increasing the oral bioavailability of SQVM. Gelucire might be considered as a promising carrier for the development of a SQVM commercial formulation. Kratz, Jadel Muller oth Kuminek, Gislaine oth Heller, Melina oth Konig, Ricardo Augusto oth Micke, Gustavo Amadeu oth Koester, Letícia Scherer oth Simões, Cláudia Maria Oliveira oth Enthalten in Elsevier Science Amna, Syeda ELSEVIER Role of sulfur in combating arsenic stress through upregulation of important proteins, and 2020 an international journal on the science and technology of wet and dry particulate systems Amsterdam [u.a.] (DE-627)ELV005093252 volume:269 year:2015 pages:200-206 extent:7 https://doi.org/10.1016/j.powtec.2014.09.012 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U FID-BIODIV 42.00 Biologie: Allgemeines VZ AR 269 2015 200-206 7 045F 660 |
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10.1016/j.powtec.2014.09.012 doi GBVA2015023000024.pica (DE-627)ELV029397480 (ELSEVIER)S0032-5910(14)00800-6 DE-627 ger DE-627 rakwb eng 660 660 DE-600 630 640 580 VZ BIODIV DE-30 fid 42.00 bkl Caon, Thiago verfasserin aut Oral saquinavir mesylate solid dispersions: In vitro dissolution, Caco-2 cell model permeability and in vivo absorption studies 2015transfer abstract 7 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier The aim of this study was to investigate the effects of solid dispersions (SDs) containing a mixture of PVP K30 and different carriers (PEG 4000 or Gelucire® 44/14) on in vitro dissolution and intestinal permeability of saquinavir mesylate (SQVM), and to evaluate their impact on the oral bioavailability of SQVM in a dog model by comparing with Svir® (commercial formulation). Although hydrophilic carriers such as PEG may provide advantages in terms of drug release, their limited solubilization capacity led to precipitation of drug and therefore to a reduced and variable oral bioavailability, as observed for SQVM from this carrier. On the other hand, self-emulsifying systems composed of Gelucire® 44/14 or oleic acid/Castor oil mixture (Svir®) were more effective at improving oral bioavailability of SQVM (approximately 5-fold higher than PEG-based formulations), probably due to the improved solubility of SQVM in GI tract, reduced particle size and inhibitory effects on P-gp (a 2.3-fold reduction of efflux ratio). The selection of carriers and other excipients which display a solubilizing effect and inhibitory effect on P-gp seems to be key factors for increasing the oral bioavailability of SQVM. Gelucire might be considered as a promising carrier for the development of a SQVM commercial formulation. The aim of this study was to investigate the effects of solid dispersions (SDs) containing a mixture of PVP K30 and different carriers (PEG 4000 or Gelucire® 44/14) on in vitro dissolution and intestinal permeability of saquinavir mesylate (SQVM), and to evaluate their impact on the oral bioavailability of SQVM in a dog model by comparing with Svir® (commercial formulation). Although hydrophilic carriers such as PEG may provide advantages in terms of drug release, their limited solubilization capacity led to precipitation of drug and therefore to a reduced and variable oral bioavailability, as observed for SQVM from this carrier. On the other hand, self-emulsifying systems composed of Gelucire® 44/14 or oleic acid/Castor oil mixture (Svir®) were more effective at improving oral bioavailability of SQVM (approximately 5-fold higher than PEG-based formulations), probably due to the improved solubility of SQVM in GI tract, reduced particle size and inhibitory effects on P-gp (a 2.3-fold reduction of efflux ratio). The selection of carriers and other excipients which display a solubilizing effect and inhibitory effect on P-gp seems to be key factors for increasing the oral bioavailability of SQVM. Gelucire might be considered as a promising carrier for the development of a SQVM commercial formulation. Kratz, Jadel Muller oth Kuminek, Gislaine oth Heller, Melina oth Konig, Ricardo Augusto oth Micke, Gustavo Amadeu oth Koester, Letícia Scherer oth Simões, Cláudia Maria Oliveira oth Enthalten in Elsevier Science Amna, Syeda ELSEVIER Role of sulfur in combating arsenic stress through upregulation of important proteins, and 2020 an international journal on the science and technology of wet and dry particulate systems Amsterdam [u.a.] (DE-627)ELV005093252 volume:269 year:2015 pages:200-206 extent:7 https://doi.org/10.1016/j.powtec.2014.09.012 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U FID-BIODIV 42.00 Biologie: Allgemeines VZ AR 269 2015 200-206 7 045F 660 |
| allfieldsGer |
10.1016/j.powtec.2014.09.012 doi GBVA2015023000024.pica (DE-627)ELV029397480 (ELSEVIER)S0032-5910(14)00800-6 DE-627 ger DE-627 rakwb eng 660 660 DE-600 630 640 580 VZ BIODIV DE-30 fid 42.00 bkl Caon, Thiago verfasserin aut Oral saquinavir mesylate solid dispersions: In vitro dissolution, Caco-2 cell model permeability and in vivo absorption studies 2015transfer abstract 7 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier The aim of this study was to investigate the effects of solid dispersions (SDs) containing a mixture of PVP K30 and different carriers (PEG 4000 or Gelucire® 44/14) on in vitro dissolution and intestinal permeability of saquinavir mesylate (SQVM), and to evaluate their impact on the oral bioavailability of SQVM in a dog model by comparing with Svir® (commercial formulation). Although hydrophilic carriers such as PEG may provide advantages in terms of drug release, their limited solubilization capacity led to precipitation of drug and therefore to a reduced and variable oral bioavailability, as observed for SQVM from this carrier. On the other hand, self-emulsifying systems composed of Gelucire® 44/14 or oleic acid/Castor oil mixture (Svir®) were more effective at improving oral bioavailability of SQVM (approximately 5-fold higher than PEG-based formulations), probably due to the improved solubility of SQVM in GI tract, reduced particle size and inhibitory effects on P-gp (a 2.3-fold reduction of efflux ratio). The selection of carriers and other excipients which display a solubilizing effect and inhibitory effect on P-gp seems to be key factors for increasing the oral bioavailability of SQVM. Gelucire might be considered as a promising carrier for the development of a SQVM commercial formulation. The aim of this study was to investigate the effects of solid dispersions (SDs) containing a mixture of PVP K30 and different carriers (PEG 4000 or Gelucire® 44/14) on in vitro dissolution and intestinal permeability of saquinavir mesylate (SQVM), and to evaluate their impact on the oral bioavailability of SQVM in a dog model by comparing with Svir® (commercial formulation). Although hydrophilic carriers such as PEG may provide advantages in terms of drug release, their limited solubilization capacity led to precipitation of drug and therefore to a reduced and variable oral bioavailability, as observed for SQVM from this carrier. On the other hand, self-emulsifying systems composed of Gelucire® 44/14 or oleic acid/Castor oil mixture (Svir®) were more effective at improving oral bioavailability of SQVM (approximately 5-fold higher than PEG-based formulations), probably due to the improved solubility of SQVM in GI tract, reduced particle size and inhibitory effects on P-gp (a 2.3-fold reduction of efflux ratio). The selection of carriers and other excipients which display a solubilizing effect and inhibitory effect on P-gp seems to be key factors for increasing the oral bioavailability of SQVM. Gelucire might be considered as a promising carrier for the development of a SQVM commercial formulation. Kratz, Jadel Muller oth Kuminek, Gislaine oth Heller, Melina oth Konig, Ricardo Augusto oth Micke, Gustavo Amadeu oth Koester, Letícia Scherer oth Simões, Cláudia Maria Oliveira oth Enthalten in Elsevier Science Amna, Syeda ELSEVIER Role of sulfur in combating arsenic stress through upregulation of important proteins, and 2020 an international journal on the science and technology of wet and dry particulate systems Amsterdam [u.a.] (DE-627)ELV005093252 volume:269 year:2015 pages:200-206 extent:7 https://doi.org/10.1016/j.powtec.2014.09.012 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U FID-BIODIV 42.00 Biologie: Allgemeines VZ AR 269 2015 200-206 7 045F 660 |
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10.1016/j.powtec.2014.09.012 doi GBVA2015023000024.pica (DE-627)ELV029397480 (ELSEVIER)S0032-5910(14)00800-6 DE-627 ger DE-627 rakwb eng 660 660 DE-600 630 640 580 VZ BIODIV DE-30 fid 42.00 bkl Caon, Thiago verfasserin aut Oral saquinavir mesylate solid dispersions: In vitro dissolution, Caco-2 cell model permeability and in vivo absorption studies 2015transfer abstract 7 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier The aim of this study was to investigate the effects of solid dispersions (SDs) containing a mixture of PVP K30 and different carriers (PEG 4000 or Gelucire® 44/14) on in vitro dissolution and intestinal permeability of saquinavir mesylate (SQVM), and to evaluate their impact on the oral bioavailability of SQVM in a dog model by comparing with Svir® (commercial formulation). Although hydrophilic carriers such as PEG may provide advantages in terms of drug release, their limited solubilization capacity led to precipitation of drug and therefore to a reduced and variable oral bioavailability, as observed for SQVM from this carrier. On the other hand, self-emulsifying systems composed of Gelucire® 44/14 or oleic acid/Castor oil mixture (Svir®) were more effective at improving oral bioavailability of SQVM (approximately 5-fold higher than PEG-based formulations), probably due to the improved solubility of SQVM in GI tract, reduced particle size and inhibitory effects on P-gp (a 2.3-fold reduction of efflux ratio). The selection of carriers and other excipients which display a solubilizing effect and inhibitory effect on P-gp seems to be key factors for increasing the oral bioavailability of SQVM. Gelucire might be considered as a promising carrier for the development of a SQVM commercial formulation. The aim of this study was to investigate the effects of solid dispersions (SDs) containing a mixture of PVP K30 and different carriers (PEG 4000 or Gelucire® 44/14) on in vitro dissolution and intestinal permeability of saquinavir mesylate (SQVM), and to evaluate their impact on the oral bioavailability of SQVM in a dog model by comparing with Svir® (commercial formulation). Although hydrophilic carriers such as PEG may provide advantages in terms of drug release, their limited solubilization capacity led to precipitation of drug and therefore to a reduced and variable oral bioavailability, as observed for SQVM from this carrier. On the other hand, self-emulsifying systems composed of Gelucire® 44/14 or oleic acid/Castor oil mixture (Svir®) were more effective at improving oral bioavailability of SQVM (approximately 5-fold higher than PEG-based formulations), probably due to the improved solubility of SQVM in GI tract, reduced particle size and inhibitory effects on P-gp (a 2.3-fold reduction of efflux ratio). The selection of carriers and other excipients which display a solubilizing effect and inhibitory effect on P-gp seems to be key factors for increasing the oral bioavailability of SQVM. Gelucire might be considered as a promising carrier for the development of a SQVM commercial formulation. Kratz, Jadel Muller oth Kuminek, Gislaine oth Heller, Melina oth Konig, Ricardo Augusto oth Micke, Gustavo Amadeu oth Koester, Letícia Scherer oth Simões, Cláudia Maria Oliveira oth Enthalten in Elsevier Science Amna, Syeda ELSEVIER Role of sulfur in combating arsenic stress through upregulation of important proteins, and 2020 an international journal on the science and technology of wet and dry particulate systems Amsterdam [u.a.] (DE-627)ELV005093252 volume:269 year:2015 pages:200-206 extent:7 https://doi.org/10.1016/j.powtec.2014.09.012 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U FID-BIODIV 42.00 Biologie: Allgemeines VZ AR 269 2015 200-206 7 045F 660 |
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Enthalten in Role of sulfur in combating arsenic stress through upregulation of important proteins, and Amsterdam [u.a.] volume:269 year:2015 pages:200-206 extent:7 |
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Role of sulfur in combating arsenic stress through upregulation of important proteins, and |
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Caon, Thiago @@aut@@ Kratz, Jadel Muller @@oth@@ Kuminek, Gislaine @@oth@@ Heller, Melina @@oth@@ Konig, Ricardo Augusto @@oth@@ Micke, Gustavo Amadeu @@oth@@ Koester, Letícia Scherer @@oth@@ Simões, Cláudia Maria Oliveira @@oth@@ |
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Oral saquinavir mesylate solid dispersions: In vitro dissolution, Caco-2 cell model permeability and in vivo absorption studies |
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The aim of this study was to investigate the effects of solid dispersions (SDs) containing a mixture of PVP K30 and different carriers (PEG 4000 or Gelucire® 44/14) on in vitro dissolution and intestinal permeability of saquinavir mesylate (SQVM), and to evaluate their impact on the oral bioavailability of SQVM in a dog model by comparing with Svir® (commercial formulation). Although hydrophilic carriers such as PEG may provide advantages in terms of drug release, their limited solubilization capacity led to precipitation of drug and therefore to a reduced and variable oral bioavailability, as observed for SQVM from this carrier. On the other hand, self-emulsifying systems composed of Gelucire® 44/14 or oleic acid/Castor oil mixture (Svir®) were more effective at improving oral bioavailability of SQVM (approximately 5-fold higher than PEG-based formulations), probably due to the improved solubility of SQVM in GI tract, reduced particle size and inhibitory effects on P-gp (a 2.3-fold reduction of efflux ratio). The selection of carriers and other excipients which display a solubilizing effect and inhibitory effect on P-gp seems to be key factors for increasing the oral bioavailability of SQVM. Gelucire might be considered as a promising carrier for the development of a SQVM commercial formulation. |
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The aim of this study was to investigate the effects of solid dispersions (SDs) containing a mixture of PVP K30 and different carriers (PEG 4000 or Gelucire® 44/14) on in vitro dissolution and intestinal permeability of saquinavir mesylate (SQVM), and to evaluate their impact on the oral bioavailability of SQVM in a dog model by comparing with Svir® (commercial formulation). Although hydrophilic carriers such as PEG may provide advantages in terms of drug release, their limited solubilization capacity led to precipitation of drug and therefore to a reduced and variable oral bioavailability, as observed for SQVM from this carrier. On the other hand, self-emulsifying systems composed of Gelucire® 44/14 or oleic acid/Castor oil mixture (Svir®) were more effective at improving oral bioavailability of SQVM (approximately 5-fold higher than PEG-based formulations), probably due to the improved solubility of SQVM in GI tract, reduced particle size and inhibitory effects on P-gp (a 2.3-fold reduction of efflux ratio). The selection of carriers and other excipients which display a solubilizing effect and inhibitory effect on P-gp seems to be key factors for increasing the oral bioavailability of SQVM. Gelucire might be considered as a promising carrier for the development of a SQVM commercial formulation. |
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The aim of this study was to investigate the effects of solid dispersions (SDs) containing a mixture of PVP K30 and different carriers (PEG 4000 or Gelucire® 44/14) on in vitro dissolution and intestinal permeability of saquinavir mesylate (SQVM), and to evaluate their impact on the oral bioavailability of SQVM in a dog model by comparing with Svir® (commercial formulation). Although hydrophilic carriers such as PEG may provide advantages in terms of drug release, their limited solubilization capacity led to precipitation of drug and therefore to a reduced and variable oral bioavailability, as observed for SQVM from this carrier. On the other hand, self-emulsifying systems composed of Gelucire® 44/14 or oleic acid/Castor oil mixture (Svir®) were more effective at improving oral bioavailability of SQVM (approximately 5-fold higher than PEG-based formulations), probably due to the improved solubility of SQVM in GI tract, reduced particle size and inhibitory effects on P-gp (a 2.3-fold reduction of efflux ratio). The selection of carriers and other excipients which display a solubilizing effect and inhibitory effect on P-gp seems to be key factors for increasing the oral bioavailability of SQVM. Gelucire might be considered as a promising carrier for the development of a SQVM commercial formulation. |
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