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Insights into the Role of Polymer-Surfactant Complexes in Drug Solubilisation/Stabilisation During Drug Release from Solid Dispersions

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ABSTRACT

Purpose

To evaluate the role of polymer-surfactant interactions in drug solubilisation/stabilisation during the dissolution of spray-dried solid dispersions and their potential impact on in vivo drug solubilisation and absorption.

Methods

Dissolution/precipitation tests were performed on spray-dried HPMC-Etravirine solid dispersions to demonstrate the impact of different surfactants on the in vitro performance of the solid dispersions. Interactions between HPMC and bio-relevant and model anionic surfactants (bile salts and SDS respectively) were further characterised using surface tension measurements, fluorescence spectroscopy, DLS and SANS.

Results

Fast and complete dissolution was observed in media containing anionic surfactants with no drug recrystallisation within 4 h. The CMCs of bile salts and SDS were dramatically reduced to lower CACs in the presence of HPMC and Etravirine. The maximum increases of the apparent solubility of Etravirine were with the presence of HPMC and SDS/bile salts. The SANS and DLS results indicated the formation of HPMC-SDS/bile salts complexes which encapsulated/solubilised the drug.

Conclusions

This study has demonstrated the impact HPMC-anionic surfactant interactions have during the dissolution of non-ionic hydrophilic polymer based solid dispersions and has highlighted the potential relevance of this to a fuller understanding of drug solubilisation/stabilisation in vivo.

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ACKNOWLEDGMENTS AND DISCLOSURES

The authors would like to acknowledge STFC for provision of neutron beamtime and Drs Stephen King and Sarah Rogers for their technical support and the financial support from Pharmaceutical Research and Development, Johnson & Johnson, Belgium. The authors would also like to thank Prof. Duncan, Q.M. Craig, Jody Voorspoels, Marcus Brewster for their constructive discussion, and Dr Francesca Baldelli Bombelli from the University of East Anglia for her assistance on DLS data processing.

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Authors and Affiliations

  1. School of Pharmacy, University of East Anglia, Norwich, Norfolk, NR4 7TJ, UK

    Sheng Qi, Claudia Pigliacelli & Madeleine Rogerson

  2. School of Chemistry, University of Bath, Bath, BA2 7AY, UK

    Steve Roser & Karen J. Edler

  3. Pharmaceutical Research and Development, Johnson & Johnson, Beerse, Belgium

    Ilse Weuts & Sigrid Stokbroekx

  4. SEPS Pharma, Ghent, Belgium

    Frederic Van Dycke

Authors
  1. Sheng Qi
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  2. Steve Roser
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  3. Karen J. Edler
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  4. Claudia Pigliacelli
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  6. Ilse Weuts
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  8. Sigrid Stokbroekx
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Correspondence to Sheng Qi.

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Qi, S., Roser, S., Edler, K.J. et al. Insights into the Role of Polymer-Surfactant Complexes in Drug Solubilisation/Stabilisation During Drug Release from Solid Dispersions. Pharm Res 30, 290–302 (2013). https://doi.org/10.1007/s11095-012-0873-7

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  • DOI: https://doi.org/10.1007/s11095-012-0873-7

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