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The following message was posted to: PharmPK
I need your expert opinion on this question. I understand that the drug
in solution as part of a liquid dosage form doesn't require dissolution
and disintegration and will pass quietly through the stomach into the
intestine.
A small lipophilic drug which administered per orally in solution form,
the rate-limiting step for absorption is gastric-emptying.
True or False.
Regards,
Naushad
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The following message was posted to: PharmPK
Hi Naushad
> I understand that the drug in solution as part of a liquid dosage form
doesn't require dissolution and disintegration and will pass quietly through
the stomach into the intestine.
I think you are assuming that the administrated drug in solution stays in
solution, however this may not be necessarily true and for many drugs
precipitation can happen in particular when the drug reaches small intestine
(e.g. weak basic drugs).
> A small lipophilic drug which administered per orally in solution form,
the rate-limiting step for absorption is gastric-emptying.
Assuming precipitation is not an issue, you have made another assumption
that the drug permeability is high. Please note that if permeability is
relatively low then in addition to gastric-emptying the small intestine
transit time can become a rate limiting factor for absorption, please see
figure 3 in the following paper:
http://www.pharmagateway.net/ArticlePage.aspx?DOI=10.1208/s12248-009-9099-y
Regards
Masoud
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Dear Naushad,
In my opinion the statement is wrong. Presence of fat in the intestine will influence the rate of absorption of small lipophilic compounds and not their emptying rate from the stomach.
Best wishes,
Khalid M Alkharfy
College of Pharmacy
King Saud University
Riyadh, Saudi Arabia
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The following message was posted to: PharmPK
Dear Naushad,
A solution formulation of drug does not mean that the drug will remain in solution in git after peroral/oral administration. It can remain in solution however, if the solubility of the drug is pH-independent; or else, the dose administered is so low, that the dissolved fraction always remains above the pH solubility curve; or else if the constituents of the formulation are good enough to keep it in solution at the administered dose during its transit through varying pH of gastro-intestinal tract. In this scenario, the rate limiting step for absorption could predominantly be gastric emptying.
In a different scenario however, the drug despite being administered as a solution, may phase out from solution due to either to pH dependent solubility (either at gastric or intestinal pH) or dilution of solubilizer used to keep the drug in solution and then dissolution can equally be important specially if it precipitates/disproportionate at intestinal pH.
A pH solubility profile therefore is a useful information to have before making assessment in this direction. However, in both these situations, the role of pre-systemic metabolism is not considered.
Hope this will answer your queries.
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Dear Nushad,
You are right it does not require disintegration or dissolution and pass through stamach rapidly to intestine. Please look at the class of the drug in Biopharmaceutics Drug classification system. and also consider that stomach is Fed state or empty and the pKa value of the drug.
Dr Zafar
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