#Circadium Rhythms

[justashadetalkative]

Status

Well, needless to say, writing didn’t happen this weekend. Sorry y’all! Combo of being out of town yesterday, then yet more family business + sheer exhaustion knocking me flat today, fff.

In all honesty I think I’m just gonna have to play things by ear this month. I’d like to get back to writing soon! But at the moment, I’m barely even glancing at the dash most days. I’m still sorting out where various things can fit into my routine now that I’m trying not to let myself stare at my phone all day and night, hah.

[aeoneris]

being on tumblr in the 2010s is what actually made me become aware of narcolepsy/hypersomnia bc of ppl talking about it and going to a sleep study to get my diagnosis. Weirdly though the meds i was prescribed then didn't work well, i've only gotten better in recent years when the adhd and hashimoto's disease got treatment (which explains. a lot lmao) but sometimes i do get fits usually with pms where i physically can't stay awake and i still can't believe ppl don't experience that. like in hindsight it's horrifying and also i still wind up sleeping for 15 hours on weekends. like so much of my life goes to waste bc i can't stop sleeping so much

[rhineboycowstone]

I love working the graveyard shift because 65% of the time it’s like. Mm yes, “working” (sitting in the office doing nothing because we finished the night’s task hours ago).

No gods no supervisors no rules just stay barely conscious enough to be woken up when someone calls over the radio

[unlicensed-field-medic]

can you tell the time without a watch? and do you have your own internal compass? and do you wake up n' sleep with the sun? and does daylight savings mess you up? and are you weak during eclipses? and are you stronger during summer solstice? are you a portable furnace? do you burst into flames when you're burnt out? do you hate the winter? are you bothered by these questions? should i stop? do you like mitski?

[Will blinks as the questions are thrown at him one after another before holding up his hands] im not bothered, just hold on or im going to forget them.

[Will starts counting on his fingers as he answers the questions] for the time thing, it depends? Like if im outside and the suns out kind of but only like to the hour or half hour its not that accurate.

[He shakes his head as he counts up again] and no i just use common sense. Sun rises in the east and sets in the west but its more north during summer and more south in winter. [Will seems genuinely unaware that this perhaps is not common sense]

Oh, this one is actually used to [will says, glad he can give a positive answer for once] my circadium rhythm is crazy strong so I have all these lamps in the infirmary for late nights. I can still sleep during the day if I have to technically but it feels like literally anyone breathing will wake me up so its not really worth it.

[That joy of a positive answer quickly fades though] yeah, no i hate daylight savings. They're not saving anything, just confusing people and making me late for things when I do sleep.

[Will pauses then, trying to remember before shaking his head] yeah, no, sorry I really dont pay attention to that, I have no clue

And im stronger in the summer [will lowers his hand as he loses count, going a bit more rapid fire] but the summer solstice doesnt specifically make me like super powerful or anything.

I am actually super warm, its pretty nice. Ive been told apparently I give good hugs because of it.

Flames seems a bit dramatic. Burnt out mentally wont do anything weird. Magically though I just tend to get really feverish and hot. Which im a lot more resilient to so it can get... pretty high. Furnace high. But I dont think ive ever reach flame high before passing out first.

I mean i dont hate it. I like the snow, which we dont really get in camp but whatever. Its just the seasonal depression and all. I dont think that has anything to do with... actually it might be an apollo kid thing now that I think about it.

I dont hate them. Im just confused if youre about to send an assassin after me or something. So you can keep going or stop either way.

I mean yeah she has nice music, its not really my favorite though

[the-litwtc-archivist]

Episode 1: Sex, Drugs, and Yugioh Cards

Below the cut is all of my notes from the first episode of LITWTC. Be forewarned, it is long.

Characters/Creatures

Mole people

- Live underground

Gigaworms

- Gigantic 3 headed earthworms

- Live underground

- They will get you if your bunker is not fortified enough

Dig boys

- Live underground

Children of the Drill

- Live underground

Flesh-eating irradiated zombies

- They come out of the ground at the graveyard and everywhere

- If you take away the gravestones at the graveyard, they won’t know where the surface is, so they might just dig down forever

- They’ve got rotten brains

- They were brought back to life through dark science and the folies of man

Vampires

- They’ll get in if they want to get in

- They can get into “your house” without permission, because it is not your house, it is a dwelling and that is a myth that is not true

- You need spiritual defenses against them, not physical ones

-- Garlic

-- Puttanesca Sauce

-- The blood of a priest

-- Smear these things on the threshold of your front door 

- You might want to let them in, and get bit to become a vampire for the advantages

- They worry about the sunlight as much as anybody else

-- Although, it might be difficult to have interpersonal relationships if you want to drink everyone’s blood

Locusts 

- 9 legs

- 15 eyes

- 12 feet tall

- 4 arms

- Very strong

- Speak spanish 

- They will have eaten most people

Teenagers

- Susceptible to glass

Giant mosquitos

6 headed lions

- Originated in Africa

- Very fast

- Very strong

- 4 arms

- Can swim

- Might be able to fly, might have wings

War boys

- If you listen to LITWTC after the apocalypse you will have to become Chris and Will’s war boys

- There are many war boys subcategories, such as madmax war boys, bone veil war boys, and war boys with 4 arms who are very strong

- You will never be able to see their faces because they will be covered up by the shroud of pain which is made of chainmail of human bone

- If you’re 7 feet tall and have fake abs then the war boys will follow you, for they respect your power and you will lead them into Valhalla

- If you’re small and weak then you run because they will chain you to their cars and use your blood

Dead Horses

- Some dead horses will rise from the dead due to radiation

- These horses will be carnivorous

Events

N/A

Setting/General Universe/Fun Facts

There will be blood tornadoes

There will be a lot of sand

- If you don’t expose yourself to sand, your skin will never become coarse and caloused

There will be omega waves

You gotta go through the fire in order to become the diamond

People in bunkers will be weak and unprepared

You can avoid blood poisoning by being in a bunker 

Being underground is not better than being above it

You’re gonna want to fortify your home

- Ex: Use tombstones as a barricade

Graveyards will be a meeting place for death cults, street toughs, teenagers (but now they’ve got swords), all kinds of unsavory elements

- Without the gravestones, they won’t know to congregate there

You’re gonna want to keep your windows covered/boarded up

- Windows are bad news, nobody wants ‘em

- You might wanna see the sun, but the sun can kill you and will only be coming out in short bursts in order to kill you

- Windows will inhibit your ability to sleep in the most effective way

- Glass is sharp, there will be many explosions, it might cut you

The only thing protecting you from the deadly ultraviolet rays of the sun will be the thick cloud of radioactive ash that covers the sun at all hours

- There will be a hole in this miasma, if you go near this hole your skin will be burned off

This world will be better than the world we currently live in, by a long shot

Circadium rhythms are no longer important in the world to come, neither is vitamin D

You should be taking 20 minute naps throughout the day to maximize the time you’re awake, and thus the amount of time that no one can stab you in the back and take your goods

- AKA The Pomodoro method

Throw out all your glass items

- Glass is sharp, there will be many explosions, it might cut you

- Use it as defense against the teenagers

The death cults are not very concerned about pain

- They might have glass sticking out of them that they put there

The world to come will not be run by the jews 

There is no love in the wasteland, only pleasure

- You may find something that reminds you of love in that pleasure, but do not mistake it for that because you cannot trust anyone except yourself, Chris Dunne, and Will Wood

- If you allow yourself to trust you will wake up chained to a radiator, missing a kidney which they took so they could sell it to the War Boys and you can’t get mad because you were gonna do the same thing

- Love is one of the things we will have to sacrifice in the world to come

Familial love may exist, but will be difficult to achieve

- Your babies will be ugly, very strong, and have many arms

- Many terrible sons with many powerful arms

Love might still exist, but it will be difficult and an unfamiliar form of love

- It could look like you and the corpse of your mother in your attic for 20 years

- Stealing your partner’s kidney and selling it to the warboys could be worked into your idea of love

- Never ever forget that they are waiting to betray you and you can have an intimate relationship

- In the wasteland, you find love wherever you can

Many people will have 4 arms and be very strong, or have radioactive blood, or skin made of stone, or have 8 arms and be very very strong

There’s going to be steam everywhere

- Things will run on steam again

Abandon your morals, you might want to hold people ransom

Speed dating in the future

- You will pay a person to facilitate it, they will give you options, 

There will be no police and no government similar to what we know as government today

In order to get Lexapro, you should drive to where they make Lexapro when the world ends

- Bring bullets, PVC pipes, 2x4s, a suit of armor that you made from trash cans, and a handful of glass to protect yourself from the other people at the Lexapro factory who had the same idea

- Your access to quality healthcare will be dependent on the resources you have 

- If you have a lot of purified water and bullets you’ll be able to get what you need

-- You can trade them for Lexapro 

-- Or, stock up on Lexapro to become the future’s pharmacist

-- Lexapro = water and bullets

Eventually Lexapro will no longer exist and you will need to find alternatives, ways to make yourself happy 

- Ex: blood horniness

-- Like bloodlust but horny, as a hobby

Kinkshaming won’t exist in the world to come

There will no longer be any social norms to abide by

See what drugs you can cook up in your basement, because if you can make drugs and bombs, you’ll be a king in the world to come

If you have many Yugioh cards you should hang on to them if you think you can use them

Money will have no value, spend all your money on Yugioh cards or whatever

- Magic the Gathering cards

- A gun

- A water purifier

There will be no gender binary

- Your dad won’t tell you what to wear anymore because he’ll be dead, a zombie, or a crossdresser. Your dad is gay and you will finally get to know him in the world to come

Everybody will be gay in the world to come, you won’t be able to afford not to be

God did this because of you, because of your nature, because of the darkest corners of your psyche, because of the things that we all hold deep down within our eids, because of the evil that lies in wait for all of us

God didn’t do this, we did.

Self hate will be very important, you want to be realistic about what behavoirs lead you to the situation you’re in

You should shoot ammonia into your veins and/or eyes

Don’t beat a dead horse, but do beat a dead horse that rose from the dead because of radiation. Only beat a dead horse if it’s coming for you, and beat it as hard as you can

Anything that comes back to life will be carnivorous

Fun Facts About Chris and Will (and the podcast itself)

Will strangles a cat now and again

God tried and failed to stop them from doing this podcast

Chris and Will will both survive the event, and so will you if you follow their instructions

[theotherwesley]

My sleep disorder is the bafflement of science. "it's like you don't even have a circadian rhythm" they say. WRONG. My circadiums have too much rhythm. they're syncopated, they're changing time signatures mid track, they're tuned to the solar cycle of the Experimental Jazz Fusion Planet, it's about the sleeps they don't play. sorry we're too sophisticated for you babes, I have to pass out for twenty hours and wake up feeling dead, it's noon 💅

[scottsafail]

Was listening to this broadcast today with Lynn Peeples, who recently wrote a book on an experiment she did looking into circadium rhythms. Including spending time in an underground bunker and exposing herself to Alaska's 24-hour sunlight.

I'm both shocked and not at all surprised by what they found. including how daylight saving time disrupts our circadian rhythms and how, depending on where you live in your current timezone, it could affect you from rates for cancer all the way to having statistically lower wages.

If you have the time to listen to the full broadcast, I fully recommend it. If not, they do summarize some main points, AND did I mention she's written a book. Haven't read it yet, so I can't speak for what's in it, but wanted to share!

[muburn]

General Drawing: Dusk & Trashcan

It's been a whole month since I last finished a drawing? Yikes, where did my motivation go?

Dusk and Trashcan present an interesting dichotomy to dissect. Given Dusk's general proactiveness, she's tried to make Trashcan more outgoing herself, efforts that bore little fruit.

The first pose has the two sharing a moment and a drink together. In quieter moments, Dusk will often share a drink with Trashcan, and he's more than happy to relax with her. The drawing process was simple enough, and I managed to get a proper grasp on how I want the eyes to look.

The second pose (the right-most one) has Trashcan throw Dusk. The two, on occasion, duel in friendly sparring sessions, and Trashcan is regularly able to get Dusk on the floor, though she's more than happy to continue; she enjoys both the duel, and the experience she gets out of it.

With regards to the drawing process of this pose, it was an interesting challenge. Since both the hair and clothes have to react with the movement of the characters wearing them, I had to draw them accordingly. The throw itself is called 'tomoe-nage'. I chose it because it's my favourite of the judo throws. When I originally drafted the poses, Trashcan's arm not only completely covered his entire face, but also part of Dusk's. Some compromises had to be made so that Dusk's face was completely visible. I would draw motion arcs on Dusk's legs to signify fast movement, but I couldn't get it to look good, so I just drew a simple arrow to convey direction of movement. I also experimented with pupil size to convey shock, leaving a bit of the 'eye outline' so it would be more in-line to how I draw eyes. All in all, I'm really happy with how it turned out.

The third pose has Dusk carry Trashcan in a fireman's carry. Trashcan is pretty much nocturnal, and he sleeps from 6h to 14h. His sleeping quirks don't stop there, though; this Circadium rhythm is absolute. The lesser of two problems is that it's practically impossible to wake him up while he's asleep, short of a natural disaster occurring, and if his sleep is somehow interrupted, he ends up feeling horrible throughout the day. However, what this also means is that, if he's not careful, Trashcan can just pass out while doing something else when the clock strikes six. Dusk, the earliest riser, took upon the opportunity to carry Trashcan to bed if he's passed out.

Unless he's up a tree. Then Anchor or Powder Keg can take care of that.

This pose in particular was... a rollercoaster to draw. A mishmash of overlapping limbs, hair, body parts, tails and equipment, this is where the layering system of digital drawing really shows its strengths. Nevermind drawing the actual poses, the arrangement of layers was a challenge in of itself. It took a really long time to get it to look good, but I am exceptionally happy with the end result. Sure, Dusk's arms may look a little janky, sure, Trashcan's bow is barely visible, sure, the carry itself is flawed, but the fact that I managed to draw something as structurally complicated as this really makes me proud of myself.

Overall, the relationship of Dusk and Trashcan is of two people who are more than happy to share a moment together, to spend time to relax and enjoy the small things in life, and to care for and look out for each other.

y'know, if i manage to get dusk's hair wrong not once, but twice, you'd imagine i'd try a hairstyle where lefts and rights isn't an issue

[iventshitsorrylmao]

i just want to throw my head cannon out there, i think that in warrior cats dewdrops are seen as "starclan remnants" cats that miss their loved ones are surrounded by stars each morning, as if their kin has visited them, protected them in their sleep. so over time more and more cats in each generation felt more at peace and hopeful during battles if they seen morning dew, at least in my headcannon this is why clan cats have evolved to have a different circadium rhythm. especially since cats are far more sensitve to light than us, so seeing a forest or field full of dewdrops in the dawn would be even more as if they're walking amongst the stars themselves. because of the extra shimery qualities and staying power of frost, it's seen as one of the better parts of leaf bare, starclan is with them for longer if not to guide them to prey then at least as encouragement and solidarity.

so dewdrops and frost are spiritually significant, so cat's with "dew" or "frost" in their prefix or suffix are seen as visited or touched by starclan.

so all this to say, imagine the extra betrayal mothwing would've felt when her own brother so accepted and beloved by his clan and named after the star's remnants themself, perverted the very idea of a message from starclan.

[drsixto]

Sleep is a survival instinct and is key to physical and mental health. "Historically, we humans followed our circadian rhythm sleep-wake cycle, this meant that as the light of day started weaning, we naturally started to wind down, and consequently, as the light of day started shining upon us, we started to feel awake for the brand new day. Even Mother Nature knew when she gave us fire as a light for nighttime use, to make it as to not interfere with our circadian sleep-wake cycle." Dr. Sixto Circadium Rhythm, cha, cha, cha! What is it about the time change in the Fall that drives me especially into a state of bewilderment until the days start to feel, or start to get longer, around mid-January? I am one who counts the number of days from the time that we go back to Standard Time, the first weekend in November until December 21st, the Winter Solstice. Countdown… from then on, let there be light! Yes, yes, time is just a construct, yet it affects my mood. In the dread of “falling back” around 6:00 pm I am ready to call it a day in its entirety. And although I am not one whose life is dictated by a clock, so I can be on to “wake up” with the sunlight and “wind down” with the onsetting sunset, the hard change to our societal clock of time does have an effect when I have to be places at a certain time. In general, this time change thing throws me off. Our clocks and watches abruptly tell us now that by 4’ish the night is coming. What time is it anyway? For my primitive self, light is light and I wake up, and dark is dark, and I hibernate for the evening. Those evenings become too long and I just can’t even see straight! Historically, we humans followed our circadian rhythm sleep-wake cycle, this meant that as the light of day started weaning, we naturally started to wind down, and consequently, as the light of day started shining upon us, we started to feel awake for the brand new day. Even Mother Nature knew when she gave us fire as a light for nighttime use, to make it [fire] at lumens low enough as to not interfere with the production of melatonin and therefore not interfere with our circadian sleep-wake cycle. It is said that “way back when” during the long nights of winter, humans would trek off to slumber when the sun went down, yes as early as 4:30 let’s say, and that they then would wake around 1 or 2 am and they would have a winter sleep sort of ritual to lull themselves back to sleep until the sun rose the next morning. And to reiterate, if there was a fire, the light emitted would not send the mind into wake mode. Very interesting huh! However, in modern-day times we have too much to interrupt our circadian rhythm. Just look around you, it is nighttime and your neighborhood could look like Disneyland, all bright and cheerful. There is increasingly more light pollution and more disruption from technology screens, and we wind up trying all sorts of sleep aids, including melatonin (naturally secreted) to help us drift off to sleep. Exposure to bright artificial light in the late evening can disrupt this process and prevent your brain from releasing melatonin. This can make it harder to fall asleep. Examples of bright artificial light include the light from a TV screen, a smartphone, or a very bright alarm clock. I for one use a mask to sleep, because one small detection that the light of the sun is coming up, I am right up with it even if I went to bed late or did not get enough rest. 23andMe says that generally, I am a night person, meaning that I am in bed by 10 and up by 7 am. Pretty accurate on the getting up part, but going to sleep, ugh. There are many interruptions. Although I have an alarm set for 9:04 pm or 21:04 to start winding down, meditate, and relax, my rewards system says, ah how about just a little bit more of doing this or watching that… Sleep hygiene is paramount, and is a habit to develop. I have a routine that most nights I do follow. Yet I still have a habit

to form, an automatic response to develop when that 9:04 pm time comes around (yes 9:04, the rebel in me, not the automatic 9:05), I head for the sleeping quarters and start my sleep hygiene routine. As we age it is even more important that our sleep hygiene does not get hijacked by automatic responses… remember what I just said… well let’s just change the last part… “the alarm goes off and my reward system says, ah, just one more episode, yet my executor knows better and says, no, no, start to wind down…” this is the type of automatic response I seek to respond to every single night of the year! Our brains, geeeezzzzz. What does light have to do with it?: Now let’s bring Mother Nature into the mix, she has something to do with light! When we look at Lumens 1800 to 2200K this is a very warm light with an almost pink tone. This type of light works very well for mood lighting, lighting that isn’t stimulating, romance lighting, the list goes on. Candles, for example, have a Kelvin temperature, we refer to it as Lumens, of around 1800 to 2200K, which is also the temperature that gives off the coziest light in a room. This lighting also does not interfere with Melatonin secretion which normally occurs when exposure to the bright white light diminishes. Bright light, we understand, releases Cortisol, and we do not need heavy amounts of Cortisol released at night as Cortisol serves as a wake-up call to the body, raising our core body temperature, heart rate, and blood pressure from a sleep state, and is also a factor in normal digestion. This natural release of Cortisol needs not be confused with the over-production of Cortisol that occurs during a stress response. A stress response is a whole different story! Responding to every stress trigger we may encounter throughout a given day, whether real or perceived, causes spikes in cortisol that disrupt this important, natural rhythm. If stress is a normal part of your daily life, then this has an even greater impact on your cortisol circadian rhythm and may mean that you need extra support to reestablish a healthy hormone balance in your sleep hygiene. A recent study by researchers at the Imperial College London in England published in Nature Neuroscience suggests that practicing a bedtime routine might be even more critical than experts once thought. Preparing for sleep may be a tendency embedded in the brains of all mammals, including humans, and is part of the survival instinct.1 In Summary, so much depends on sleep to stay healthy and bright. As a Holistic Health practitioner, I can't emphasize more the importance of sleep; the importance of a routine; the importance of meditation; the importance of a personal ritual every night, and of course good sleeping quarters such as a quality mattress, inviting sheets, and avoidance of any type of screens in the bedroom, this includes television). All of this helps in getting enough sleep to feel up to the game during wake hours. As early as the 1800s, those well-versed in sleep and its effect on human functioning, yes we will call them Sleep Experts, have recommended keeping good habits of healthy sleep hygiene. For further information on how you or a loved one could benefit from a Holistic Wellness, Whole Health path, please do not hesitate to contact me at sixto@drsixto.me. To your Whole Health and Wellness, naturally! Dr. Sixto J. Sicilia Holistic Health & Nutrition Practioner Founder, issimoUSA 1Getting ready for bed controlled by specific brain wiring in mice. (2023, September 21). Retrieved Nomer 25, 2003, from Imperial News. https://www.imperial.ac.uk/news/247873/getting-ready-controlled-specific-brain-wiring/

[lesbianrey]

my favorite part of middle/high school was getting gaslit by my teachers and parents that i was crazy for not being able to wake up at 6 am every morning and be mentally alert for classes

[juniperpublishers-gjpps]

Formulation and Evaluation of Chronomodulated Drug Delivery of Montelukast Sodium--Juniper Publishers

JUNIPER PUBLISHERS-OPEN ACCESS GLOBAL JOURNAL OF PHARMACY & PHARMACEUTICAL SCIENCES

An oral press coated tablet containing Montelukast sodium was formulated with an outer barrier layer of different compositions of hydrophobic polymer eythyl cellulose and hydrophilic polymer hydroxyl propyl methyl cellulose. This press coated tablet was prepared by using direct compression and wet granulation methods in order to achieve the predetermined lag time.

Keywords: Pulsatile drug delivery systems (PDDS); Nocturnal asthma(NA); Chronopharmacology; Circadium Rhythms; Burst release; Lag time

Abbreviations: EC: Ethyl Cellulose; HPMC: Hydroxy Propyl Methyl Cellulose; FTIR: Fourier Transform Infra Red; SLS: Sodium Lauryl Sulphate; IR: Immediate Release; ChrDDS: Chrono Modulated Drug Delivery Systems; PCT: Press Coated Tablets

Introduction

Controlled drug delivery systems [1] have acquired a centre stage in the area of pharmaceutical R &D sector. Such systems offer temporal &/or spatial control over the release of drug and grant a new lease of life to a drug molecule in terms of controlled drug delivery systems for obvious advantages of oral route of drug administration. These dosage forms offer many advantages, such as nearly constant drug level at the site of action, prevention of peak-valley fluctuation, reduction in dose of drug, reduced dosage frequency, avoidance of side effects and improved patient compliance. In such systems the drug release commences as soon as the dosage form is administered as in the case of conventional dosage forms. However, there are certain conditions, which demand release of drug after a lag time. Such a release pattern is known as pulsatile release [2-5]. The diseases currently targeted for chronopharmaceutical formulations are those for which there are enough scientific backgrounds to justify ChrDDS compared to the conventional drug administration approach. These include asthma, arthritis, duodenal ulcer, cancer, diabetes, cardiovascular diseases, hypercholesterolemia, ulcer and neurological diseases [6,7].

If the organization in time of living system including man is borne in mind, it is easy to conceive that not only must the right amount of the right substance be at right place but also this must occur at the right time. In the last decade numerous studies in animals as well as clinical studies have provided convincing evidence, that the pharmacokinetics &/or the drug effects -side effects can be modified by the circadian time &/or the timing of drug application within 24 hrs of a day [8]. A pulsatile drug delivery system that can be administered at night (before sleep) but that release drug in early morning would be a promising chronopharmaceutic system. Drug targeting to colon [9] would prove useful where intentional delayed drug absorption is desired from therapeutic point of view in the treatment of disease that have peak symptoms in the early morning such as nocturnal asthma, angina, arthritis.

Circadian rhythms are self-sustaining, endogenous oscillation, exhibiting periodicities of about one day or 24 hours. Normally, circadian rhythms are synchronized according to the body’s pacemaker clock, located in the suprachiasmic nucleus of the hypothalamus [8]. Asthma is a chronic inflammatory disease of the airways, characterized by hyper responsiveness to a variety of stimuli. The role of circadian rhythms in the pathogenesis and treatment of asthma indicates that airway resistance increases progressively at night in asthmatic patients. Circadian changes are seen in normal lung function, which reaches a low point in the early morning hours. The worsening of asthma at night commonly referred to as nocturnal asthma (NA) [10]. A drug delivery system administered at bedtime but releasing drug during morning hours would be ideal in this case. Nocturnal asthma is a variable exacerbation of the underlying asthma condition associated with increases in symptoms, need for medication, airway responsiveness, and/or worsening of lung function. Generally, a reduction in peak flow or forced expiratory volume in one second (FEV1) of at least 20% is implicit in this definition. Lung function (e.g., peak expiratory flow rate or FEV1) is usually highest at 4 PM and lowest at 4 AM the latter time is generally when asthma symptoms are most prevalent. . Consequently, the administration of a drug formulated in such a delivery system, i.e. taken at bedtime with a programmed start of drug release in early morning hours, could offer a more effective therapy than a typical controlled release drug delivery system, provided that the most appropriate drugs are administrated [11].

Pharmaceutical coatings [12] are an essential tool to achieve the desired formulation of pharmaceutical dosage forms. Coating techniques mostly used in pharmaceutical industry are aqueous or organic coating, which present some disadvantages: time consuming, stability for heat labile and hydrolysis of degradable drug and polluted environment problem. Thereby, non-solvent coating is introduced as alternative coating technique to overcome these disadvantages.

For the time controlled release system from compressioncoated tablets, the amount of the outer shell is a key factor for controlling the lag time. Higher amount of the outer coating added would prolong the lag time of drug release [13].

The aim of the present investigation was to develop and evaluate an alternative, simple, orally applicable one pulse drug delivery system based on a press-coated tablet preparation. The PCT investigated in the current study consisting of a rapidly disintegrating core tablet presscoated by a barrier layer consisting of varying concentrations of Hydroxy propyl methyl cellulose (HPMC) and Ethylcellulose (EC). HPMC is a disintegrant and had been used to cause rapid disintegration of tablets. The other component of the barrier layer, Ethylcellulose (EC) is a well-known water-insoluble polymer that has long been used as a rate-controlling membrane in medication dosage forms to regulate drug release. Although EC has also been added in tablet formulations to act as a retarding material, few papers have focused on the use of EC as a directly compressible excipient. It was postulated that when the barrier layer was exposed to dissolution media, the HPMC particles swell and erode [14], a process which was retarded to varying degrees depending upon the quantity of EC present, demonstrating that manipulation of both components controls the erosion rate.

Materials and Methods

Preparation of core tablets by direct compression

The ingredients depicted in the table except colloidal silicon dioxide and magnesium stearate were dry blended for 15 minutes followed by addition of quitted ingredients and dry blended for another 5 minutes. The mixed blend of drug and excipients was compressed using a single punch CADMACH punching machine to produce round tablets weighing 100mg with a diameter of 6mm. A minimum of 50 tablets were prepared for each batch.

Preparation of press-coated tablets

The core tablets were press-coated with 400mg of prepared barrier blend as per the mentioned formulas from X1 to X5. 200mg of barrier layer material was weighed and transferred into a 13mm die then the core tablet was placed manually at the center. The remaining 200mg of the barrier layer material was added into the die and compressed.

In vitro drug release study of core tablets

The In vitro release pattern of core tablets was studied as per method given by Chaudhari SP [15] Release pattern was studied visually by taking images of the core tablets in a petri plate containing dissolution medium at the specific time intervals 5sec, 10sec, 15sec. Also the sample was analyzed at 342nm using a UV spectrophotometer.

In vitro drug release study of press-coated tablets

In-vitro dissolution studies of press coated tablets were performed at 37 ± 0.5 °C using 0.5% w/v aqueous solution sodium lauryl sulfate in USP II paddle method at 50 rpm. 5 ml of filtered aliquot was manually withdrawn at pre-determined time intervals and replaced with 5 ml of fresh 0.5% sodium lauryl sulfate solution maintained at the same temperature. The samples were analysed at 342nm using a UV spectrophotometer. The lag time and percentage release was determined of the each formulation.

Results and Discussion

Design of Pulsatile release tablet

The pulsatile drug delivery system consisted of inner core tablet containing drug reservoir and outer coating layer with combination of water insoluble polymer Ethylcellulose and water soluble polymer HPMC. Ethyl cellulose was chosen because of its swelling and rupturable behavior. HPMC was chosen because of its eroding behavior.

In vitro dissolution of core tablets

The core tablet shows 73.97 % of drug release within 9 minutes upon contact with dissolution medium, core tablet get erode and release the drug as given in Figure 1.

Analytical methods

From the standard stock solution (1000 μg/ml), appropriate aliquot were transferred to series of 10 ml volumetric flasks and made upto 10 ml with desired solvents so as to get concentration of 5,10,15,20… or 2,4,6,8… μg/ml. the absorbance of the solution were measured at 342 nm for Montelukast sodium. This procedure was performed in triplicate to validate calibration curve. A calibration curve was plotted.

Compatibility Analysis

Fourier transform infra-red spectroscopy

FT-IR spectroscopy was employed to ascertain the compatibility of drugs with polymers. The individual drug and final formulation were scanned. Both the spectra were compared for confirmation of common peaks. Montelukast sodium with polymers showed no significant variation in height, intensity and position of peaks, suggesting that drug and excipients were compatible. There is no interaction between drug and polymer. Hence, it can be concluded that the drug is in Free State and can release easily from the formulation the spectra are reported in the Table no.6.3 and Figure 6.2-6.3.

Conclusion

In the 5 trials, the optimized formulation was X2 trial which releases the Montelukast sodium immediately after a lag time. The core was compared with the pure drug where it showed 46.26 % of drug release in 15 minutes whereas core exhibited 98.96% in 15 minutes.

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[biolums]

got excited bc i got a notification. it was my phone telling me to go the fuck to sleep. lads im gonna be honest. really took the L with this one.

[unlicensed-field-medic]

We have sun lamps actually. A lot of us do have it so I set a bunch of them up on shelves and desks in the Apollo cabin. I took one to tartarus actually. Or the underworld at least [will says before hearing the next bit]

I mean its very much the dark. [Will says quickly, his face flushing, which is true. His circadium rhythm is pretty extreme, and at night it always drains him a lot until the next morning where hes usually fine.] The energizing force that is Nico doesnt factor into it [he denies, defensively turning back to the papers on his desk] and this is just night 2 so its not that bad

-Open Starter-

[Will sits at his little desk in the infirmary, a desk covered in paper that looks wrinkled and folded and much less organized than the ones he usually makes nowadays, though they're still in his handwriting. The papers are stained with old blood from years ago, which is also different than the papers he usually is seen messing with.]

[There are also like three lamps in the room all turned on extremely bright and pointed right at him in contrast with the dark of night outside the infirmary as Will flips through papers, mumbling vaguely to himself, an opague water bottle by his side]

[He doesnt even seem to notice he has company in this room, less of a room and more just curtained off with dark light-blocking sheets]

(What do you do?)

Anyone can interact

Literally please I love any interaction

[dykestache]

have made the very smart and wise decision that if i get tired today i will just simply take more adderall

[edwardslostalchemy]

Have I mentioned I'm running on less than 4 hours of sleep? I slept late and I woke up at my usual 8:30 am time and then I couldnt sleep, so I read something and then fell asleep for 30 minutes. I just couldn't sleep. So now my face hurts and I'm doing assignments. I'm surprised at how awake I am. I should be feral right now. I should be moody. I should be irritated. Instead I'm super mellow. Like I even had the patience to make myself pancakes, which is something I dont do because it takes me forever. And I've finished 2 assignments, but I need 4 more so I'll try to get that done and maybe even get a nap in because I'm typing and I suddenly forgot how to thought process so haha oops.