Probing the molecular interactions between pharmaceutical polymeric carriers and bile salts in simulated gastrointestinal fluids using NMR spectroscopy

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A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä

Date

2019-09-01

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en

Pages

8

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Journal of Colloid and Interface Science, Volume 551, pp. 147-154

Abstract

The number of poorly soluble new drugs is increasing and one of the effective ways to deliver such pharmaceutically active molecules is using hydrophilic polymers to form a solid dispersion. Bile salts play an important role in the solubilisation of poorly soluble compounds in the gastrointestinal tract (gut)prior to absorption. When a poorly water-soluble drug is delivered using a hydrophilic polymer based solid dispersion oral formulation, it is still unclear whether there are any polymer-bile salt interactions, which may influence the drug dissolution and solubilisation. This study, using two widely used hydrophilic model polymers, Hydroxypropyl methylcellulose (HPMC)and polyvynilpirrolidone (PVP), and sodium taurocholate (NaTC)as the model bile salt, aims to investigate the interactions between the polymers and bile salts in simulated fed state (FeSSIF)and fasted state (FaSSIF)gut fluids. The nature of the interactions was characterised using a range of NMR techniques. The results revealed that the aggregation behaviour of NaTC in FaSSIF and FeSSIF is much more complex than in water. The addition of hydrophilic polymers led to the occurrences of NaTC-HPMC and NaTC-PVP aggregation. For both systems, pH and ionic strength strongly influenced the aggregation behavior, while the ion type played a less significant role. The outcome of this study enriched the understanding of the aggregation behaviour of bile salts and typical hydrophilic pharmaceutical polymers in bio-relevant media. Due to the high surface-activity of the bile salts and their ability to interact with polymers, such aggregation behaviour is expected to play a role in drug solubilisation in the gut when the drug is delivered by hydrophilic polymer based dispersions.

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Keywords

Bile salts, DOSY NMR, Polymer-surfactant interaction, Poorly water-soluble drugs, Solid dispersions

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Citation

Pigliacelli, C, Belton, P, Wilde, P & Qi, S 2019, ' Probing the molecular interactions between pharmaceutical polymeric carriers and bile salts in simulated gastrointestinal fluids using NMR spectroscopy ', Journal of Colloid and Interface Science, vol. 551, pp. 147-154 . https://doi.org/10.1016/j.jcis.2019.05.002