Albendazole vs. albendazole sulphate in the fasted upper gastrointestinal lumen based on ex vivo and in vitro data

A Kourentas, M Vertzoni, Ibrahim Khadra, Gavin Halbert, Hugh Clark, James Butler, Christos Reppas

Research output: Contribution to conferencePoster

Abstract

To evaluate the impact of salt form on solubility in upper gastrointestinal (GI) lumen and on concentrations of albendazole (ABZ) in upper small intestine following oral administration of simple aqueous suspensions in the fasted state, using ex vivo and in vitro data. A crystalline stable sulfate salt of albendazole (ABZ-S) was recrystallized from tetrahydrofuran. Differential scanning calorimetry and elemental analysis confirmed the salt formation. Solubility of ABZ and ABZ-S was measured in human aspirates and in fasted state simulating gastric and intestinal fluid. GI transfer of ABZ and ABZ-S suspensions (each at two dose levels, 200 mg and 50 mg) was simulated by using an optimized in vitro methodology which has been shown to be useful in evaluating luminal events relating to the GI transfer (Psachoulias et al. Pharm Res. 2012; Symillides et al. 5 th BBBB Int. Conference, 2013). The effect of precipitation inhibitors was evaluated by including HPMC E5 and PVP (Kollidon® 30) in the suspensions. ABZ was assayed with HPLC in all cases. Equilibrium solubility data in aspirates and simulated GI fluids indicated that, compared to base, ABZ-S is at least 3 times more soluble in stomach and at least two times more soluble in upper small intestine. The in vitro transfer data indicated extensive precipitation and limited supersaturation leading to similar duodenal compartment concentrations for both ABZ and ABZ-S. By decreasing the dose to 50 mg duodenal compartment concentrations were increased. In addition, concentrations in duodenal compartment were slightly increased when HPMC E5 was included in the gastric compartment. For ABZ, a weak base which is expected to precipitate extensively in the upper small intestine, the use of a salt with clearly improved solubility characteristics in the upper GI lumen does not seem to greatly increase the concentrations in simulations of the upper small intestine. The impact of precipitation inhibitors seems to be also small. Acknowledgement This work was performed within the OrBiTo project which is funded by the Innovative Medicines Initiative Joint Undertaking under Grant Agreement No 115369. The authors would like to thank Biorelevant.com for providing SIF powder original.

Conference

ConferenceAmerican Association of Pharmaceutical Scientists
CountryUnited States
CityArlington
Period2/11/146/11/14

Fingerprint

Albendazole
Sulfates
Solubility
Small Intestine
Salts
Stomach
Suspensions
In Vitro Techniques
Povidone
Differential Scanning Calorimetry
Powders
Oral Administration

Keywords

  • albendazole
  • tetrahydrofuran
  • upper gastrointestinal lumen

Cite this

Kourentas, A., Vertzoni, M., Khadra, I., Halbert, G., Clark, H., Butler, J., & Reppas, C. (2014). Albendazole vs. albendazole sulphate in the fasted upper gastrointestinal lumen based on ex vivo and in vitro data. Poster session presented at American Association of Pharmaceutical Scientists, Arlington, United States.
Kourentas, A ; Vertzoni, M ; Khadra, Ibrahim ; Halbert, Gavin ; Clark, Hugh ; Butler, James ; Reppas, Christos. / Albendazole vs. albendazole sulphate in the fasted upper gastrointestinal lumen based on ex vivo and in vitro data. Poster session presented at American Association of Pharmaceutical Scientists, Arlington, United States.
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abstract = "To evaluate the impact of salt form on solubility in upper gastrointestinal (GI) lumen and on concentrations of albendazole (ABZ) in upper small intestine following oral administration of simple aqueous suspensions in the fasted state, using ex vivo and in vitro data. A crystalline stable sulfate salt of albendazole (ABZ-S) was recrystallized from tetrahydrofuran. Differential scanning calorimetry and elemental analysis confirmed the salt formation. Solubility of ABZ and ABZ-S was measured in human aspirates and in fasted state simulating gastric and intestinal fluid. GI transfer of ABZ and ABZ-S suspensions (each at two dose levels, 200 mg and 50 mg) was simulated by using an optimized in vitro methodology which has been shown to be useful in evaluating luminal events relating to the GI transfer (Psachoulias et al. Pharm Res. 2012; Symillides et al. 5 th BBBB Int. Conference, 2013). The effect of precipitation inhibitors was evaluated by including HPMC E5 and PVP (Kollidon{\circledR} 30) in the suspensions. ABZ was assayed with HPLC in all cases. Equilibrium solubility data in aspirates and simulated GI fluids indicated that, compared to base, ABZ-S is at least 3 times more soluble in stomach and at least two times more soluble in upper small intestine. The in vitro transfer data indicated extensive precipitation and limited supersaturation leading to similar duodenal compartment concentrations for both ABZ and ABZ-S. By decreasing the dose to 50 mg duodenal compartment concentrations were increased. In addition, concentrations in duodenal compartment were slightly increased when HPMC E5 was included in the gastric compartment. For ABZ, a weak base which is expected to precipitate extensively in the upper small intestine, the use of a salt with clearly improved solubility characteristics in the upper GI lumen does not seem to greatly increase the concentrations in simulations of the upper small intestine. The impact of precipitation inhibitors seems to be also small. Acknowledgement This work was performed within the OrBiTo project which is funded by the Innovative Medicines Initiative Joint Undertaking under Grant Agreement No 115369. The authors would like to thank Biorelevant.com for providing SIF powder original.",
keywords = "albendazole, tetrahydrofuran, upper gastrointestinal lumen",
author = "A Kourentas and M Vertzoni and Ibrahim Khadra and Gavin Halbert and Hugh Clark and James Butler and Christos Reppas",
year = "2014",
month = "11",
day = "2",
language = "English",
note = "American Association of Pharmaceutical Scientists ; Conference date: 02-11-2014 Through 06-11-2014",

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Kourentas, A, Vertzoni, M, Khadra, I, Halbert, G, Clark, H, Butler, J & Reppas, C 2014, 'Albendazole vs. albendazole sulphate in the fasted upper gastrointestinal lumen based on ex vivo and in vitro data' American Association of Pharmaceutical Scientists, Arlington, United States, 2/11/14 - 6/11/14, .

Albendazole vs. albendazole sulphate in the fasted upper gastrointestinal lumen based on ex vivo and in vitro data. / Kourentas, A; Vertzoni, M; Khadra, Ibrahim; Halbert, Gavin; Clark, Hugh; Butler, James; Reppas, Christos.

2014. Poster session presented at American Association of Pharmaceutical Scientists, Arlington, United States.

Research output: Contribution to conferencePoster

TY - CONF

T1 - Albendazole vs. albendazole sulphate in the fasted upper gastrointestinal lumen based on ex vivo and in vitro data

AU - Kourentas, A

AU - Vertzoni, M

AU - Khadra, Ibrahim

AU - Halbert, Gavin

AU - Clark, Hugh

AU - Butler, James

AU - Reppas, Christos

PY - 2014/11/2

Y1 - 2014/11/2

N2 - To evaluate the impact of salt form on solubility in upper gastrointestinal (GI) lumen and on concentrations of albendazole (ABZ) in upper small intestine following oral administration of simple aqueous suspensions in the fasted state, using ex vivo and in vitro data. A crystalline stable sulfate salt of albendazole (ABZ-S) was recrystallized from tetrahydrofuran. Differential scanning calorimetry and elemental analysis confirmed the salt formation. Solubility of ABZ and ABZ-S was measured in human aspirates and in fasted state simulating gastric and intestinal fluid. GI transfer of ABZ and ABZ-S suspensions (each at two dose levels, 200 mg and 50 mg) was simulated by using an optimized in vitro methodology which has been shown to be useful in evaluating luminal events relating to the GI transfer (Psachoulias et al. Pharm Res. 2012; Symillides et al. 5 th BBBB Int. Conference, 2013). The effect of precipitation inhibitors was evaluated by including HPMC E5 and PVP (Kollidon® 30) in the suspensions. ABZ was assayed with HPLC in all cases. Equilibrium solubility data in aspirates and simulated GI fluids indicated that, compared to base, ABZ-S is at least 3 times more soluble in stomach and at least two times more soluble in upper small intestine. The in vitro transfer data indicated extensive precipitation and limited supersaturation leading to similar duodenal compartment concentrations for both ABZ and ABZ-S. By decreasing the dose to 50 mg duodenal compartment concentrations were increased. In addition, concentrations in duodenal compartment were slightly increased when HPMC E5 was included in the gastric compartment. For ABZ, a weak base which is expected to precipitate extensively in the upper small intestine, the use of a salt with clearly improved solubility characteristics in the upper GI lumen does not seem to greatly increase the concentrations in simulations of the upper small intestine. The impact of precipitation inhibitors seems to be also small. Acknowledgement This work was performed within the OrBiTo project which is funded by the Innovative Medicines Initiative Joint Undertaking under Grant Agreement No 115369. The authors would like to thank Biorelevant.com for providing SIF powder original.

AB - To evaluate the impact of salt form on solubility in upper gastrointestinal (GI) lumen and on concentrations of albendazole (ABZ) in upper small intestine following oral administration of simple aqueous suspensions in the fasted state, using ex vivo and in vitro data. A crystalline stable sulfate salt of albendazole (ABZ-S) was recrystallized from tetrahydrofuran. Differential scanning calorimetry and elemental analysis confirmed the salt formation. Solubility of ABZ and ABZ-S was measured in human aspirates and in fasted state simulating gastric and intestinal fluid. GI transfer of ABZ and ABZ-S suspensions (each at two dose levels, 200 mg and 50 mg) was simulated by using an optimized in vitro methodology which has been shown to be useful in evaluating luminal events relating to the GI transfer (Psachoulias et al. Pharm Res. 2012; Symillides et al. 5 th BBBB Int. Conference, 2013). The effect of precipitation inhibitors was evaluated by including HPMC E5 and PVP (Kollidon® 30) in the suspensions. ABZ was assayed with HPLC in all cases. Equilibrium solubility data in aspirates and simulated GI fluids indicated that, compared to base, ABZ-S is at least 3 times more soluble in stomach and at least two times more soluble in upper small intestine. The in vitro transfer data indicated extensive precipitation and limited supersaturation leading to similar duodenal compartment concentrations for both ABZ and ABZ-S. By decreasing the dose to 50 mg duodenal compartment concentrations were increased. In addition, concentrations in duodenal compartment were slightly increased when HPMC E5 was included in the gastric compartment. For ABZ, a weak base which is expected to precipitate extensively in the upper small intestine, the use of a salt with clearly improved solubility characteristics in the upper GI lumen does not seem to greatly increase the concentrations in simulations of the upper small intestine. The impact of precipitation inhibitors seems to be also small. Acknowledgement This work was performed within the OrBiTo project which is funded by the Innovative Medicines Initiative Joint Undertaking under Grant Agreement No 115369. The authors would like to thank Biorelevant.com for providing SIF powder original.

KW - albendazole

KW - tetrahydrofuran

KW - upper gastrointestinal lumen

UR - http://www.aaps.org/Career_Center/Professional_Development/2014_AAPS_Annual_Meeting_and_Exposition_Webcasts/

M3 - Poster

ER -

Kourentas A, Vertzoni M, Khadra I, Halbert G, Clark H, Butler J et al. Albendazole vs. albendazole sulphate in the fasted upper gastrointestinal lumen based on ex vivo and in vitro data. 2014. Poster session presented at American Association of Pharmaceutical Scientists, Arlington, United States.