• N&PD Moderators: Skorpio | someguyontheinternet

Intranasal delivery: An approach to bypass the blood brain barrier

BilZ0r said:
^ Drugs don't need to be water soluble to be insuflated

Ehh...You sure 'bout that? Goes against most info here on BL, but then again, I have been out of the loop for a while... Can you elaborate on how non-water soluble drugs are absorbed through the nasal membrane?
 
They need to be lipid soluble and yeah, most of that info on BL has been wrong all along.
 
A logical extension of what you're saying is that we all can begin snorting benzos if we need a quicker onset?
 
No, you're both wrong. For one, benzos can be snorted. Secondly, ALL membranes can only be crossed by fat solubile drugs, unless there is an carrier/channel for it.

Read this post, and then get back to me.
 
BilZ0r said:
No, you're both wrong. For one, benzos can be snorted. Secondly, ALL membranes can only be crossed by fat solubile drugs, unless there is an carrier/channel for it.

Read this post, and then get back to me.


complete crap. it's the negative charge not the esterification per say or the partition coefficients that resulted in one of the esterified carboxyl moiety of L-tyrosine having faster absorption rates than regular L-tyrosine. You also have to take into account that it had to convert to the parent compound, L-tyrosine for it to be absorbed intranasally. Is this conversion going to happen for all drugs? i don't think so.

O-acyl-L-tyrosine esters and N-acetyl-L-tyrosine resulted in the same absorption rates as L-tyrosine. And you are talking only about L-tyrosine which is easily absorbed by the nasal passages esterified or not. This is not true for ALL drugs!

re-read the conclusion of your 1st study: " the differences in the rates of nasal absorption could not be attributed solely to partition coefficient. The enhancement in the rate of absorption observed for these esters was attributed instead to the absence of the negative charge on the carboxylate moiety. It is a result of this negative charge that the rates of nasal absorption of L-tyrosine, O-acyl-L-tyrosine esters and N-acetyl-L-tyrosine are similar, despite significant differences in their partition coefficients."


Your second example of benzoic acid absorption has all to due with PH of the drug! Again, it all depends on the particular drug's PH!

This is the quote from your 2nd study: "The nasal absorption of benzoic acid was found to depend on the pH of the perfusate with the benzoate anion being absorbed at a rate one-fourth of that of benzoic acid."

Obviously, there are many parameters when it comes to the absorption rates of the mucuos membrane. no one is saying that all lipid soluble drugs cannot be absorbed. But, it's just basic physiology that a water soluble drug will be much more likely to be absorbed by the thin mucous membrane of the nasal cavity. Of course there are many parameters as seen in your studies, but can you actually say that most lipid soluble drugs can be absorbed and better absorbed than a water soluble drug intranasally? no way, jose!

and what a headache that was. I've always hated reading journals and studies especially doing pubmed research papers. i'm done with grad school and finished reading all those studies and writing papers for many years now. Don't make me do it again, please!
 
I don't understand your comments in regards to the first study.

In response to your comment on the 2nd study; what else is the pH changing apart from the lipid solubility?

Do you have any comments on the third study?

I state that a drug has to be lipid soluble to be absorbed. And I stick by this fact. However, I did not refute that water soluble drugs can be absorbed via mucous membranes, and indeed, water soluble drugs can be absorbed via mucous mebranes.

But, it's just basic physiology that a water soluble drug will be much more likely to be absorbed by the thin mucous membrane of the nasal cavity.
By that I assume you mean, drugs with a lower o/w co-efficent are better absorbed. Well if this is such a basic physiologica fact, I'm sure you will have no problem finding an authoratative citation or two to support you.
 
BilZ0r said:

I'm sure you will have no problem finding an authoratative citation or two to support you.

source: DR. AznRaver

You're lucky i even read your post and responded. i don't have time to play with you anymore. maybe someone with time and formal medical/chemistry education can answer your Q's.

i gotta goto work now with my patients. maybe we can play later, but i hate reading studies for personal reasons from the past. i'm an expert at reading them, but i hate it! that's why i never became a researcher!
 
AznRaver said:
source: DR. AznRaver

You're lucky i even read your post and responded. i don't have time to play with you anymore.

I think we can all agree to be very happy about this and I'll celebrate by singing a song.
 
AznRaver said:
complete crap. it's the negative charge not the esterification per say or the partition coefficients that resulted in one of the esterified carboxyl moiety of L-tyrosine having faster absorption rates than regular L-tyrosine. You also have to take into account that it had to convert to the parent compound, L-tyrosine for it to be absorbed intranasally. Is this conversion going to happen for all drugs? i don't think so.

Uhh... What it's saying is that the the negative charge vector was interfering w/ absorption. Ions, and polar molecules don't cross membranes very well. And for the most part, lipid solubility is the best predictive tool for crossing membranes, unless there is a channel/carrier protein. For example, in the case of alkaloids, water solubility of the salt helps by maximizing interface with the membrane, but as a cation, it's not going to cross. The small amount which exists as the freebase when dissolved is what will cross (and of course this will be replaced, LeChatelier or better, like Hendelson-Hasselbach for the Dr (A title means nothing, sources mean everything in science. If you pass w/ 1 percent higher than a failing grade from med school, the person still gets the title too. Why wear your credentials on your sleeve?). BilZ0r's comments were in context.
 
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