eevee🏳️‍⚧️(the pokémon)

🏳️‍⚧️ Hunter Schafer appears in a Prada ad 🏳️‍⚧️

Right-wing men: finally, they're putting hot women in ads again!

SECTOR ://EXTRACTS In a not-to-distant future, a breakthrough in technology revolutionizes the computing - with a catch: it can't be turned off. From research to video games, developers use this advanced technology and ...

SECTOR ://EXTRACTS Chapter 2 posted! This one actually gives you a little bit instead of just being a tease 😅

www.royalroad.com/fiction/1483...

www.scribblehub.com/series/21118...

Can't believe I'm more nervous about putting this on AO3 than publishing it on KDP 😅 "Be kind, I'm new"

archiveofourown.org/works/777374...

the line that keeps going through my head and coloring my days recently has been:

“I’m fine, but I’m not okay.”

and…well….yeah.

i can't help but wonder if he's in to it and consented

uhm...lemme do some math....

*a couple minutes later*

about 5,000 to 5300 kcal (based on weight....which probably isn't the best weigh to do it but)

it does xD

did you know that the average adult human body contains about 125,000 to 150,000 kcal?

holy...wow. I. I'm kind of glad i have not even considered watching season five yet.

oof but fingers crossed! it must be so frustrating :/

I was wondering what was going on with your plex server 🫂 you got this imi!!

"In 1929, Quinn and Meyer illustrated how aspiration of these substances could occur imperceptibly: iodized oil instilled into the nose of sleeping patients was detectable on their chest roentgenograms the following morning despite an uneventful night."

this is a paper on lipoid pneumonia; it describes what it is, how it happens, and more.

an important bit: ⬇️next⬇️post⬇️

*nods* but it’s still a risk that needs to be mitigated

the aspiration risk and concurrent risk of lipoid pneumonia means oil is a no go...

side note on precipitation:

this not only means precipitation of the API in the spray bottle, but also at the time of spraying due to shear forces and directly on the epithelial surface; these last two can negatively impact absorption.

sorry to leave you in suspense...but i'll finish this later, my brain needs a bit of a break.

obligatory, none of this is advice, nor recommended, to anyone. this is just a fun brain puzzle.

...that loves water.

the idea would be to create a cyclodextrin inclusion system with progesterone encapsulated within. theoretically, this should solve the solubility and precipitation side of the problem. it should also help permeation and mucosa adhesion, but, if we add one more excipient..

6/?

cyclodextrins are cyclic oligosaccharides composed of glucose linked by glycosidic bonds. they exhibit a 3D toroidal structure with a hydrophilic outer surface and a hydrophobic cavity within, and have the ability to selectively encapsulate molecules.

eli5: cyclodextrins act as a wrapper...

5/?

thankfully, there are much better options for excipients.

so.

what we *need* is something to increase the solubility of progesterone in water, help permeation along, increase nasal residence(think glue,) and of course, reduce precipitation.

enter cyclodextrins.

4/?

...inconsistent dosing, and no guarantees on permeation, let alone consistent permeation; this is insufficient. (the one benefit of the excipient i used was it acts almost like glue but it can cause osmotic stress to epithelial cells and cause irritation(and damage) long term.)

3/?

oils are not an option due to aspiration risk and risk of lipoid pneumonia, and are not (generally) used in intranasal preparations.

so we're back to water-based.

when i first came at this problem, it was from the angle "emulsification is sufficient for delivery"...but with dubious efficacy,

2/?

since i'm thinking about it again...might as well post about my current thoughts on *how* to make a nasal progesterone spray work.

what it comes down to is a solubilization and permeation problem. progesterone is *not* water soluble and tho it *is* oil soluble, this is not an option.

1/?

I have always thought that a snuff bullet would work REALLY well for intranasal prog powder :3

ANYWAY

i am pretty keen to explore powder inhalers as a delivery mechanism for progesterone.

(this girl said 'serious' instead of 'series' lol)

progesterone isn't water soluble, but if you can get it to stay in solution using a USP emulsifier, it kinda sorta works, though efficacy is a crap shoot.

(if i could have afforded it, i would have done a serious of blood tests to see serum levels of progesterone, but alas)

I did the thing. Took me long enough 😂 Would appreciate any feedback! But yeah, trigger warning - read the tags and description before jumping in.

bsky.app/profile/ezia...

@halfbakedrhymes.com - here ya go!

if it drains me, defines me, and demands clarity…it’s a trap.