IPEC e-newsletter - Excipients Insight August 2017 - 11-08-17


Inside this issue


Gender affects excipient functionality - in rats

Researchers in the UK have demonstrated that the excipient-mediated bioavailability of a drug product can be altered by the gender of the recipient.

The team from University College London (UCL) School of Pharmacy made the observation in a study that compared various drugs formulated with polyethylene glycol 400 (PEG 400) in male and female rats. PEG 400 is widely-used to increase the solubility and bioavailability of active pharmaceutical ingredients (APIs).

They found that PEG 400 significantly increased the bioavailability in male rats compared to females for some drugs, but not others, and set out to test the hypothesis that the difference depended on interactions between the excipient and P-glycoprotein (P-gp), a molecule involved in the transport of some drugs across cell membranes.

They compared ampicillin, a drug known to be bind to P-gp and transported out of cells, to metformin, which does not interact with P-gp. PEG 400 significantly increased the bioavailability of ampicillin in male but not female rats, something that has also been seen with ranitidine, another P-gp substrate.

In contrast, there was no difference between male and female rats in the bioavailability of PEG 400-formulated metformin.  As a further test, they pre-treated the animals with a P-gp inhibitor - cyclosporin A - and found that this eliminated the differences between the genders for ampicillin and ranitidine, and had no effect on metformin bioavailability.

"The work reported in this paper further enhances our understanding of the influence of the supposedly inactive excipient PEG 400 on drug bioavailability," write the authors in the European Journal of Pharmaceutical Sciences

"Given that many compounds are P-gp substrates and/or modulate P-gp activity, increasing attention to this topic is needed for an optimal usage of excipients."




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