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In Vitro Gastrointestinal Lipolysis of Four Formulations of Piroxicam and Cinnarizine with the Self Emulsifying Excipients Labrasol® and Gelucire® 44/14

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Abstract

Purpose

Labrasol® and Gelucire® 44/14 are defined admixtures of acylglycerols and PEG esters which are substrates for digestive lipases.

Methods

We investigated their in vitro gastrointestinal lipolysis to understand which compounds are, after digestion, responsible for keeping poorly water-soluble drugs in solution. The precipitation of piroxicam and cinnarizine formulated in these excipients during the gastrointestinal lipolysis was also studied.

Results

Monoacylglycerols and PEG monoesters are the largest compounds present at the end of gastric phase whereas PEG-monoesters are the largest compounds after the duodenal phase. The precipitation of piroxicam is mainly due to the gastric lipolysis. In the control experiments performed without digestive lipases, cinnarizine formulated in Labrasol® was found to precipitate upon dilution of the gastric medium to form the solution mimicking the duodenal medium. In the presence of gastric lipase, Labrasol® was hydrolyzed and the precipitation of cinnarizine was not observed in this case. When the cinnarizine was formulated with Gelucire® 44/14 the precipitation was only due to the dilution of the gastric medium.

Conclusion

Our study highlights the importance of the gastrointestinal lipolysis and the associated phenomena such as the dilution of chyme by biliary and pancreatic secretions in vivo, on the solubilisation of poorly water-soluble drugs formulated with lipid-based excipients.

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ACKNOWLEDGEMENTS

We are grateful to Cédric Miolane and Christophe Voustinas for their help for the HPLC analysis of piroxicam and cinnarizine, respectively. Sylvie Fernandez’s PhD research was supported by a CIFRE contract from Association Nationale de la Recherche Technique (ANRT, France).

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Authors and Affiliations

  1. Laboratoire d’Enzymologie Interfaciale et de Physiologie de la Lipolyse, CNRS UPR 9025, 31 chemin Joseph Aiguier, 13402, Marseille cedex 20, France

    Sylvie Fernandez & Frédéric Carrière

  2. Gattefossé SAS, 36 chemin de Genas, 69804, Saint-Priest, France

    Sylvie Fernandez, Stéphanie Chevrier, Nicolas Ritter, Bruno Mahler, Frédéric Demarne & Vincent Jannin

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  1. Sylvie Fernandez
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  2. Stéphanie Chevrier
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  3. Nicolas Ritter
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  6. Frédéric Carrière
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  7. Vincent Jannin
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Correspondence to Vincent Jannin.

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Fernandez, S., Chevrier, S., Ritter, N. et al. In Vitro Gastrointestinal Lipolysis of Four Formulations of Piroxicam and Cinnarizine with the Self Emulsifying Excipients Labrasol® and Gelucire® 44/14. Pharm Res 26, 1901–1910 (2009). https://doi.org/10.1007/s11095-009-9906-2

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