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Does oral semaglutide adsorb measurably to the vial wall at 4 mg/mL?

Asked 9 Sept 2024Modified 22 months agoViewed 14k times
6

For reference: oral semaglutide · 4 mg/mL.

I would like the arithmetic checked rather than the conclusion asserted.

I have deliberately not used an online calculator because I want to be able to check the result.

What is the general form of this calculation?

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JE
askedjonas_ekstrom12k389 Sept 2024

2 Answers

Accepted answer first, then by votes
69

Accepted answer

4 mg/mL is 4000 µg/mL — roughly 400 times the concentration at which surface adsorption is measurable. Losses to glass and plastic matter in the low microgram-per-millilitre range, where a monolayer on the wall is a real fraction of what is in solution. At 4 mg/mL that same monolayer is a rounding error. If you see an apparent loss at this concentration, suspect the dilution step or the assay before you suspect the wall.

Answer first: the degradation pathways worth knowing are hydrolysis, deamidation, oxidation, aggregation and adsorption, and each has a different trigger and a different mitigation.

Adsorption onto glass and plastic is significant at low concentrations — micrograms per millilitre — and negligible at milligrams per millilitre. It is the usual explanation for an apparent loss in a dilute preparation.

Oxidation targets methionine, cysteine and tryptophan, adding sixteen daltons per oxygen. It is catalysed by trace metals and promoted by dissolved oxygen and by light.

Aggregation at air-liquid interfaces is established from surface-tension and particle-count studies and is the basis for anti-agitation handling guidance.

Sequence determines which pathways apply, so general statements are general.

Cold, dry, dark, still. Those four words cover most of the mitigation.

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KA
answered · acceptedkwn_analytical147k35820 Sept 2024
2I have kept vials both ways for a year and this matches what I saw. – helena_vidmar 36 days ago
3Does the same reasoning apply to material already in solution, or is that a different curve? – bac_or_bust 3 months ago
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58

The honest answer is that most reported "degradation" is adsorption and dilution error rather than chemistry.

Hydrolysis cleaves the backbone, most readily at aspartate-proline and aspartate-glycine sequences, and is acid-catalysed. In a dry solid it barely proceeds at all.

Freeze-thaw cycling drives aggregation through concentration at the ice interface and pH shifts as buffer components crystallise out at different rates. Each cycle costs something.

Adsorption losses at low concentrations are quantified in formulation studies and are the reason carrier proteins are used in dilute preparations.

Nothing here is medical advice, and research-use compounds are not approved for human use.

At dilute concentrations, suspect adsorption before you suspect chemistry.

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EV
answeredekaterina_volk21k281 Oct 2024

Your answer

Ask PeptideStack is a static archive. Posting is closed, but the norms are worth stating: answer the question that was asked, show your working, cite the trial or the certificate, and say plainly where the evidence runs out.

Not medical advice. Research-use-only compounds are not approved for human use.