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Oh god what have I done?? Liquid suspension gone wrong?


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I made a liquid solution, I thought I did it right... started it 2 days ago.

 

Ativan .5mg per pill

1.125mg  (1 1/8 pill) per day

 

divided by 3 doses per day

1 dose = .375mg (3/4 of a pill)

 

30 day/90 dose Batch = 67.5 pills

 

thoroughly mixed 67.5 pills into 90mL of ORA-Plus solution

 

each dose of 1mL solution should = .375mg ativan right?

 

I've been having new horrible withdrawals ever since switching over.

 

This makes no sense of why I'm withdrawing so bad as if I dropped my dosage.  Being in the middle of a mild panic attack right now isn't helping, lol.

 

I haven't been stirring after the initial stirring... I assumed I don't have to with the ORA-Plus solution.

 

Any feedback is welcome.

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Hi DrugFreeGoals :hug:

 

each dose of 1mL solution should = .375mg ativan right?

I came up with the same result too.

 

I've been having new horrible withdrawals ever since switching over.

This makes no sense of why I'm withdrawing so bad as if I dropped my dosage.

It's normal. Many buddies have reported the same thing here in BB. While in few benzo forums it talks about a loss of about 5-10% by jumping to all liquid, many others reported a cold-turkey-like effect. It is likely your case and there is an explanation for it.

 

1.  Medicines must get where they need to go to do their work, without being lost in other areas of the body. Tablets, capsules, liquids, powders, suspensions, injections, and enemas are some of the key delivery modes to get the medicines into our bodies so they can do their jobs. Most of the medicines need protection from the harsh stomach environment, which could lower the effects, damage or at worst destroy them before they get a chance to work.

The enteric coating placed on tablets and capsules, a polymer barrier applied on oral medication, is a means of managing medication within the body by preventing its dissolution or disintegration in the gastric environment. In case of benzo, by its consistency and formulation the coating allows delayed release in the small intestine. By breaking and dissolving those tablets to prepare our solution, the coating is destroyed together with other excipients as binders, disintegrators ...While the deterioration of inactive ingredients will have little impact, the more time benzo as active component remains exposed in the "hostile" stomach environment, the more vulnerable it becomes to loss of efficacy.

 

2. Contrarily to a PG/alcohol "dissolved" solution, when taken as a "suspended" solution by using a dense suspended oral vehicle as ORA-Plus, a new player comes into the game. When you drink your dose, the dense solution is treated as food, the same way as with milk, fruit juice...It rapidly transits from the mouth where the slightly acidic saliva combines with the suspended solution and starts to break it down. When you swallow the suspended solution, it travels down the esophagus into the stomach. The pyloric sphincter separating the stomach from the small intestine closes to force the suspended solution to remain in the stomach and be digested by stomach acid. Gastric juices in the stomach come then into the game to break down the suspended solution further and kill any living bacteria. Then the pyloric sphincter opens and the stomach sends the processed suspended solution into the small intestine, where nutrients are absorbed. The small intestine is ideal for absortion work as it presents a much larger surface area for absorption compared to the stomach.

During the time it passed in the stomach environment, suspended solution as food has been submitted to the churning action of the stomach muscles that physically crushes and mixes the food combined with the acids and enzymes for the chemical breakdown of food. Since benzo can’t move into the small intestine immediately, this considerably reduces the absorption of benzo into the bloodstream.

 

What happens when alcohol is used as solvent instead of a suspended solution? Most alcohol absorption into the body happens in the small intestine. The solution will in this case rapidly transit by the empty stomach, where it leaves behind a small quantity due to the acid environment, to finish into the small intestine where it is absorbed into the bloodstream with minimum loss. From a dose viewpoint, this is the method that preserves most of the initial quantity.

 

What happens when the stomach is NOT empty? If one drinks benzo solution with food in the stomach, the solution will be considered as part of the food and together with existing food will be retained and processed in the stomach until it is ready to pass to the small intestine. Its efficacy will definitely reduce following this treatment although the enteric coating could minimize this loss. The same principle applies when the solution is a viscous compounded solution or a thick fruit juice taken right after to "wash". They will be both considered as food and will undergo the same treatment as food with the tablet broken pieces completely exposed with no coating in case of suspended solution.

 

To further clarify the different ways our digestive system treats "solid" food and "liquid" food, let's take the example of people who drink alcohol with empty stomach vs during a fatty meal. Actually the way the meal is processed by our stomach can reduce the peak blood alcohol concentration (BAC) up to 50% relative to that produced when alcohol is consumed in an empty stomach. This explains why it is easier to get intoxicated with the same quantity of alcohol when the stomach is empty.

 

How to minimize this problem?

Take the dose with most part in tablet where feasible, and the cut part in liquid. As 1 dose = .375mg (3/4 of a pill), take 1/4 pill in liquid (0.125mg) and 1/2 pill (0.250mg) as tablet. When the liquid part has been tapered off, then replace the next tablet 1/4 part by liquid and so on. Meanwhile your body has the time to gently adapt to the new solution.

 

Wish you all the best!

:smitten:

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Hello, DrugFreeGoals.

 

I know it’s scary but please take a deep breath.  You will be ok. We will help you figure this out but we need more information from you to do so. 

 

(1) How do you dose?  How many times a day?  What times? What amounts?

 

(2) When you switched to all liquid, did you also reduce your dose or did you keep it the same?

 

(3) What specific steps did you follow to prepare your homemade liquid?

 

For example, did you grind your regular tablets into a powder using a mortar and pestle first?  Did you then transfer the powder to a different container before adding the Ora-Plus?  What else? 

 

I ask because your homemade liquid may not have the concentration you think it does due to what pharmacists refer to as compounding loss. Based on what I’ve read in the medical literature, this can be as much as 10%. 

 

So, by switching to all liquid, all at once, you may have made up to a 10% reduction in your dose (or more if you also reduced your dose).  So, an increase in withdrawal symptoms is understandable.  It may take a while for them to settle down.

 

Fortunately, moving forward, there are strategies you can use to minimize compounding loss, including a clever technique developed by a team of pharmacists at the University of Utah College of Pharmacy, Primary Children’s Medical Center in Salt Lake City, and Children’s Hospital of Philadelphia. I’ll include the reference and URL below.  See the section titled “Preparation of Lorazepam Suspensions” on page 255.

 

You also might consider using a combination of regular tablets and liquid (many members do this).  But we need to know your daily dosing schedule to determine if this is a possibility for you.

 

I’ll end with one last note:

 

What you are preparing is a suspension, not a solution. So it is extremely important that you agitate your liquid vigorously before you measure your dose.

 

Reference

 

Wan-Man Ellaria Lee, Ralph A. Lugo, William J. Rusho, Mark MacKay, and John Sweeley. (2004). Chemical Stability of Extemporaneously Prepared Lorazepam Suspension at Two Temperatures. The Journal of Pediatric Pharmacology and Therapeutics: October 2004, Vol. 9, No. 4, pp. 254-258. Accessed online at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3469120/pdf/i1551-6776-9-4-254.pdf

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I'm so upset that this did not work out as planned (ofcourse a lot of that feeling is the withdrawals' influence).

 


 

Thank you Jim Hawk

 

As I'm in withdrawals right now I'm going to have to re-read your post several times to get it into my brain, but very interesting.  And I like the technique you posted at the end.  I think I'll do that.

 


 

Thank you Libertas.

 

I'm very fortunate though that I happen to have a large cache of spare pills.  I can't image my psychiatrist would write me a duplicate script because I screwed this up.

 

PRE-SOLUTION

 

For each dose I was cutting a .5mg pill in half, then one of the halves again, to achieve 3/4 pill for .375mg.  The pills are get crumbly and I rarely got an exact amount.

 

9am .375mg

2pm .375mg

7pm .375mg

 

I would let the dose dissolve under my tongue.

 

SOLUTION PREPARATION

 

When I switched to liquid I kept the same dose amount and dosing times.

 

1 pill = .5mg

aim was to make a 30 day (90 dose) supply.

weighed 10 pills to get an average weight per pill of .06 grams.

calculated .06g (pill weight) x (.75) x 90 doses = 4.050g of pills

 

NOTE: last night (2 days after using the solution) I weighed an equivelant 67.5 pills to check the weight and it ended up coming out to 4.146 for a difference of .096 per batch, which is ~2% higher than what I used for my solution

 

grinded up my entire bottle of 270 pills with a pill crusher and then into a fine powder with steel mortar.

 

calibrated my scale, then tared the scale with the scale's small cup.

 

weighed out 4.05g of pills into the scale's cup.

*I did not use the 50g weight while weighing because the manufacturer states it is accurate > .005g.

 

used a 10mL syringe to transfer 90mL of oragel into a 4oz glass canning jar.

 

using the syringe, transferred small amount of oraplus gel from the 90mL in jar to the powder in the cup to create a paste (I forgot where I read to do this this)

 

using a measuring spoon, I scraped the paste from the scale cup into the 90mL in jar. dunked the scale cup in the solution several times and then tapped it out and scraped with spoon to get as much of it as possible into the solution.

 

In hindsight it would have been way better to have put the powder in the jar first, then make a paste and then add the remaining 90mL so there was less transferring loss.

 

I store the solution at room temperature

 

DOSING

 

When dosing, I use 100% of a 1mL syringe to extract and squirt into my mouth and swallow.

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Jim,

 

I’m going to be facing this cross to liquid in a few months. Right now, I’m battling a manufacturer change that is making me very sick .

 

Your solution by starting with 25% of dose as liquid and 75% as tablet is great.  How would I prepare 25% of the 1 mg liquid solution. I’m going to use whole milk.

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Hi Magnolis :hug:

 

Jim,

 

I’m going to be facing this cross to liquid in a few months. Right now, I’m battling a manufacturer change that is making me very sick .

 

Your solution by starting with 25% of dose as liquid and 75% as tablet is great.  How would I prepare 25% of the 1 mg liquid solution. I’m going to use whole milk.

Point me to a thread of yours and I'll reply from there.

:smitten:

 

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I made a liquid solution, I thought I did it right... started it 2 days ago.

 

Ativan .5mg per pill

 

thoroughly mixed 67.5 pills into 90mL of ORA-Plus solution

 

each dose of 1mL solution should = .375mg ativan right?

 

 

If you mixed 67 pills into 90 mL of ora-plus, my guess is your suspension is more than 90 mL. It could almost be 100 mL. 67 pills is (assuming 0.15 grams per pill) around 10 grams of pills! Not sure what the compact density of 67 pills would be. 10 grams of water is 10 mL. Your suspension concentration could be off by 10%. So you might have made a 10% jump.

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Hi DrugFreeGoals,

 

With Ora-Plus used as Oral Suspension Vehicle, a threshold during the mix with water must be respected. Water volume must NOT exceed 50% of the total solution to preserve the suspending capability of the liquid. Said differently, the most diluted solution allowed is 50% Ora-Plus + 50% water. I want to make sure your solution respects this constraint.

 

By the number of tablets you crushed, you must have really many tablets to use! Have you ever thought to prepare for just a few days, say 3, to make sure it works first?

 

Should you decide to taper with combined liquid+tablets then you will need much less liquid. Having large volume prepared may last more than you actually need.

:smitten:

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Hello again, DrugFreeGoals.

 

HopeToDoThis has made a good point.  The volume of the liquid you prepared might be more than 90mL due to the large number of tablets you combined with a relatively small volume of Ora-Plus.

 

Thank you for providing more details about how you prepared your homemade suspension.  I’m no expert but it seems to me you could simplify your procedure, minimize compounding loss, and minimize the volume issue HopeToDoThis has raised by considering the method Lee et al (2004) used. Here’s a topline summary:

 

Mark an appropriately sized bottle with a fill line.*

Put the tablet(s) in the bottle.

Add the minimum amount of sterilized water needed for tablet dispersion.

Shake the bottle until a slurry is formed.

Add the volume of suspending vehicle(s) needed to reach the fill line.

Press an adapter cap into the bottle opening.

Shake the bottle vigorously.

Measure the desired dose using an oral syringe.

 

*The fill line mark depends on the total volume of liquid (water + suspending vehicle) needed to achieve the desired concentration of liquid.

 

 

Do you know or could you find a trusted pharmacist who would be willing to consult with you about using the above method?

 

Thank you also for sharing your dosing schedule. If you decide to use a combination of regular tablets and liquid to taper, here’s a daily dosing schedule for your consideration:

 

Dose 1: 0.25mg in tablet form + 0.125mg in liquid form

Dose 2: 0.25mg in tablet form + 0.125mg in liquid form

Dose 2: 0.25mg in tablet form + 0.125mg in liquid form

 

You would reduce your dose via the liquid portion. The amount you reduce will be determined by the taper rate (the rule of thumb in this community is 5-10% of your current dose every 10-14 days) and taper interval (daily, weekly, every other week, every month) you choose to use.

 

If your 0.5mg tablets have a functional score line, it’s ok to split them in half.  Just be sure to take the resulting half tablets consecutively to ensure you are ingesting the full amount of the active drug substance in any given tablet.

 

Sending all best wishes your way for a successful taper ... Libertas

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I made a liquid solution, I thought I did it right... started it 2 days ago.

 

Ativan .5mg per pill

 

thoroughly mixed 67.5 pills into 90mL of ORA-Plus solution

 

each dose of 1mL solution should = .375mg ativan right?

 

 

If you mixed 67 pills into 90 mL of ora-plus, my guess is your suspension is more than 90 mL. It could almost be 100 mL. 67 pills is (assuming 0.15 grams per pill) around 10 grams of pills! Not sure what the compact density of 67 pills would be. 10 grams of water is 10 mL. Your suspension concentration could be off by 10%. So you might have made a 10% jump.

 

HopeToDoThis!!!!... This was one of those things in the back of my mind and was like 'huh... oh it'll be fine' and you nailed it.  Only exception is that my 67.5 pills weighs at ~4.146g... so more like 4.1%... but still enough to cause big unintended withdrawals!

 

I'm also curious/concerned about what the volumetric conversion between powder and liquid is so we may be a little off there too... Maybe a quick web search. 

 

As a result, I think with a little more research, I'd be more comfortable adding ~.4146g to the mixture, call it a day and go back to the 100% liquid dose.

 

Hello again, DrugFreeGoals.

 

HopeToDoThis has made a good point.  The volume of the liquid you prepared might be more than 90mL due to the large number of tablets you combined with a relatively small volume of Ora-Plus.

 

Thanks Libertas, I was concerned about making such a concentrated dose.  My motivations were purely based on being being cheap and not wanting to buy 10x as much oroplus to make 10mL doses.  I knew making such a concentrated mix would increase the risk.

 

Mark an appropriately sized bottle with a fill line.*

Put the tablet(s) in the bottle.

Add the minimum amount of sterilized water needed for tablet dispersion.

Shake the bottle until a slurry is formed.

Add the volume of suspending vehicle(s) needed to reach the fill line.

Press an adapter cap into the bottle opening.

Shake the bottle vigorously.

Measure the desired dose using an oral syringe.

 

*The fill line mark depends on the total volume of liquid (water + suspending vehicle) needed to achieve the desired concentration of liquid.

 

 

I agree with everything except, the oroplus is very viscous and I don't believe shaking it will distribute the drug particles, I think vigorous stirring will be best.

 

---

 

As outlined by Jim Hawk, there's also other factors that may influence it too.  I was letting the pill disolve under my tongue to get it directly into my bloodstream.  Whereas I was immediately swallowing the solution.  It may be best for me to hold the solution under my tongue for 60 seconds in hopes that it will get into my bloodstream faster. 

 

I would love to know if anyone has any good info on if a solution like the one I made can be absorbed sublingually as well as via the pill powder.

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You would want to confirm this, but I have read that OraPlus retains its suspending properties when diluted up to 50% with water.
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Hi All,

 

Update:

Thank you all (HopeToDoThis, Libertas) for your help with troubleshooting and educating me about liquid tapers.  I found that two factors could have contributed to my horrible wds. 

1. I was adding the powder after measuring the liquid and not compensating for that... so I've made a minor adjustment for that.

2. I wrongfully assumed that the oraplus was a true suspension and after the initial shaking I wouldn't have to shake it any more.  Well... I shook it up at night... all the particles settled down to the bottom, and for 2 days I was skimming from the TOP of the solution, pretty much guaranteeing I got zero dose for about 2 days. 

 

I've now fixed those problems and will start tapering soon.

 

So I'm at (Ativan)

9am .375mg (1mL liquid)

2pm .375mg (1mL liquid)

7pm .375mg (1mL liquid)

 

I'll make a post in tapering support to ask what the best plan of attack is.

 

With Ora-Plus used as Oral Suspension Vehicle, a threshold during the mix with water must be respected. Water volume must NOT exceed 50% of the total solution to preserve the suspending capability of the liquid. Said differently, the most diluted solution allowed is 50% Ora-Plus + 50% water. I want to make sure your solution respects this constraint.

 

Hi Jim Hawk (just noticed your reply)

 

Since oroplus calls for a 50% mixture with a sweetening syrup, and since I can't have sugar and I'm so sensitive to various things, I didn't want to take a chance with their sugar free sweetening chemicals, I decided to go for a 100% oroplus mixture.  Have I created a problem using pure oroplus?

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  • 2 weeks later...

How to minimize this problem?

Take the dose with most part in tablet where feasible, and the cut part in liquid. As 1 dose = .375mg (3/4 of a pill), take 1/4 pill in liquid (0.125mg) and 1/2 pill (0.250mg) as tablet. When the liquid part has been tapered off, then replace the next tablet 1/4 part by liquid and so on. Meanwhile your body has the time to gently adapt to the

Quote

 

I want to do this technique. Is cutting 1/4 of pill going to compromise it?

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Cutting the pill in any way (at least with the kind i have) would compromise the accuracy of the dosage because the pills are so small and they crumble when cut.
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