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Everyone and welcome to another video tutorial now in this presentation. Well be looking looking at reconstitution calculations all right so there are some apis and drugs that their very nature are unstable in the aqueous environment. Even when being exposed for short periods of time an example would be your entire biotics.
These are classic examples of drugs that are unstable in ets environment and so to increase or enhance the shelf life of these types of drugs. They are typically prepared or formulated as a dry powder. So they go through a freeze drying process or a line of fertilization process to get them as a dry powder.
The thing about these kind of drugs is if you are going to use them power and tea. Really you need to basically and put them back in to true solution before you can inject them so thats where we constitution comes into the picture. The constitution is essentially the process through which you take a dry powdered drug and completely dissolve.
It using a diluent and typically the diluent that youll be using a sterile water for injection back to your static water for injection and so on so you add a specified volume based on the formulation parameters to the of diluent to the dry powder and that gives you your reconstituted preparation you just want to keep in mind. That your final reconstituted solution should be free from particulates of any kind and should basically be clay those are few things you want to keep in mind all right so in this tutorial. Well be looking at the sources of the diluent.
I mean whered you get the information. How much volume of diagram to add well look at that then i will take you to take you to three strategic initial method examples one will illustrate how you calculate powder volume and ill talk about that parameter down the line and then the other example. Well look at how you determine the dose calculation.
Once you have got a reconstituted preparation. And then the last example will illustrate how you compute the volume of dial. And given the other variables.
Alright so before we get into the main calculation section on some level. We are all familiar with reconstitution. A classic example would be the kool aid and which typically most kids really love alright.
So when you look on the package. It gives you some directions. It tells you how much water to use to dissolve a packet of the kool aid.
So that you get the flavor so it tells you to use for each packets just put that into a. 169 flower ounce bottle of water or 05. Liters of liter bottle of water add the packet to it dissolve.
It and then you should have your kool aid. Now for most people actually tastes okay and that would be a certain specified concentration alright. But if its too sweet for you you probably would then add a little bit more water.
So that its good for your taste. And that means it to be more diluted and if you like it extra sweet you probably will use a little bit less of the water that has been specified so just keep that analogy in mind as we go through some of the examples that we need to look at all right so first of all lets talk about where we find the information on how much volume of diluent to add the first place you get that information is on the vial label. So the label has the devourer have a label and on that label.
Most of the time you find how much volume to use so in this example way of the zithromax powder it tells you under to constitute to a hundred milligrams per milliliter with 48. Ml of sterile water for injection. So the volume to add has been given as four point eight milliliters now for the a few of us who already be curious.
And we note that this is a 500 milligram. Preparation how do you then add. 48.
Mls. And ill end up with a hundred milligrams per milliliter. Thats because the paradise is contributing some volume and in this case.
I can tell its point two. But well look at powered up on him down the line. So the first place to find that information is on the label of the vial all right now.
Sometimes you do not find the information on the vial like in this example it gives you a whole bunch of information. It tells you you have one gram of cefazolin. But you notice that there is no place on the vial label that you see the volume to add so in this instance.
What you want to do is look at the additional place. Where you can find that information and that will be in the package insert all right so im going to just show. You what you find out on the package.
Insert so now. When the package insert this is a for the product that i just showed you im just going to quickly take you to the page. Because i know it where the way.
This is on page eleven here say just go to it you navigate nicely through. Which it tells a whole bunch of good information. The doors in and so on.
But for this particular time youre interested in how much volume to add so where it says preparation of solutions of test csf. We can see how much diluent to add if we look at the second column so in the second column. It gives us amount of diamonds to be added.
And it tells you what to do whether you are given intramuscularly or intravenously. So for i am on intramuscular injection for the one gram vial. It tells you to add three millimeters and once you do that the total volume in there will be about 36.
Ml. And then youll find our concentration is to 18 milligrams. Per.
Milliliter. Now notice that if we are given an iv infusion for the one gram and two gram vasya required to add 10 ml of the diluent. However your final concentrations are slightly different for the one gram iv.
If you infusion you end up with a final volume of about ten point six and your concentration. Is 95 milligrams. Per.
Ml. And you notice for the two gram. You end up with about 180 milligrams per.
Ml as concentration. So the second place you can find information on how much volume to add is in your package. Insert so now that that is clear lets talk about powder volume.
So we notice in a few of the examples that even though were given the amount of volume to add if we simply divided the quantity of the dry powder in the vial by that volume. Well end up with a different concentration than what was specified now that difference actually has to do with what is known as powered up volume. So parallel volume is essentially the space or volume occupied by the powder in the dry powder preparation so there are some instances.
Where you find out that the power of volume is negligible. So your volume of the diluent would essentially be the same as the final volume and an example would be what we see when we look at the val size 125 milligram in this particular table the diluent volume was 1 ml our final volume is 1 ml. And so the peridot volume the contribution from the powder is essentially zero all right now.
There are several instances where the volume of the powder is not negligible. It actually contributes some significant amount and so you wanna factor that into consideration because it effects in some ways your final concentration. Thats what would have little effect so we look at the five hundred.
Milligrams you add 18. Ml of diluent. You end up with a final volume of 2.
Ml and the part of volume is 02. Ml. Thats because you subtract the diluent of the volume of the diluent from the final.
Volume to determine the powder volume same thing for the 2. Grams. 68.
Ml of diluent gives you final. Volume of 8. Ml and you end up with the powder volume of 12.
So there is more significant apart of volume. The more difference to make in terms of factoring that in when you calculating the final concentration. So this actually is the most important equation.
When it comes to computing or calculations. Involving reconstitution and it says your final volume is equal to the volume of the diluent plus. The paddle volume all right so this equation is what you want to have stenciled in your mind.
Okay so i already talked about how the final volume is equal to volume of dye 11. Plus padovani. However you will notice that there sometimes.
When you do these calculations that they dont i mean directly give you the final volume and then students always get confused to what do i do now so. What i recommend is a variation of this equation. And that would be understanding that the final volume is related to the quantity of the drug and the final concentration.
Those three parameters all are interrelated and so the way you could also think about it is to notice that your final volume is equal to the quantity of the drug divided by the final concentration. So if you understand our relationship and you substitute that information into the original equation you come up with a derivative of that equation. Which i find to be more than fish out to students when it comes to some types of calculations regarding country constitution okay so thats this quantity of our final concentration equals volume of diluent plus power volume is a very powerful equation that you can use all right so now well jump into those three examples.
I was talking about well first start off by looking at the calculation. Involving and determine the powder volume. And then well look at the next example where we are using the reconstituted preparations concentration to determine the dose force particular patient and then in the third example well look at how you determine the volume of diluent given the other parameters presented in the equation all right so lets jump right in all right.
So the question like i was saying says one gram of substance. A dime must be diluted with three ml sterile water for injection prior to ensure muscle. Administration.
The resulting solution contains a thousand. Im 218 milligrams. Per ml.
What is the powder volume of the drug. All right so notice that youve been given a few numbers in here the 1 gram is the original quantity of drug in the vial. The 3 ml is the volume of your diluent and the 280 milligrams per milliliter is your final concentration.
So we are supposed to find the powder volume all right so the equation that you want to use is says. Final volume should be equal to the volume of your diluent. Plus.
The powder volume. But like i said you are not given your final volume directly so we want to use that derivative that i was recommending this is something i teach all the students that i come across and that would be the quantity of your drug divided by the final concentration should be equal to the volume of the diluent plus. The powder volume and so we do know the final concentration is to 18 milligrams.
Per. Milliliter and our quantity is 1 gram. So just to keep the units consistent.
We want to convert the grams to milligrams. And a gram is a thousand milligrams. So a thousand milligrams divided by 2 80.
Milligrams per. Milliliter should be equal to the volume of your diluent. Which is 3 ml.
Plus. What we do not know the power down volume and so according to the calculator and a. Thousand divided by.
280 that should give us about 35. 7. Equals.
3. Ml plus x. And so we can easily solve for our unknown.
If we subtract.
3 point. 5 from both sides. Okay.
So. This will imply that x. Equal to 3.
Point. 5. 7.
Minus. 3 and that should be equal to. 057.
Mmm all. Right so the powder volume in this instance is going to be 05. 7.
Ml. Okay so just a recap notice that we start you want to use this form of the equation quantity of dry divided by final concentration equals volume of diluent of a powder volume thats because your final volume is basically the same as this ratio right here okay. So we do that the other key thing to note was we converted the grams to milligrams.
So that the units are consistent and then the rest was a he substituted the ratio based be calculated on the use calculator ended up. With. 35 ml and then we subtracted that 3 from.
35 to get 05. 7. Ml.
So that would be the volume or a part of volume in this particular example all right so lets look at the next example. Which talks about those calculations from reconstituted medications. So now.
Lets take a look at the second example. Which actually involves determining those calculation. Once you have the final concentration of a reconstituted.
Preparation so he says a medication order calls for 400000 units. Of penicillin g. Sodium to be added to one liter of d5w available and the pharmacy is a vial containing five million units.
The manufacturer directions are to add 8 ml of diluent to get a concentration of 500000 units per ml. How many milliliters of the we constitute a solution will be needed to prepare the other all right so at first glance you have so much going on. Here so many different numbers you have 400000 units.
You have 1 liter you have 5 million. Units you have 8 ml you have the concentration 500000 units per ml so what do you do all right now whenever you you have a situation where youre calculating the dose. And you know the final concentration.
You basically simply just set up a ratio thats what you do all right so were going to look at this equation we can analyze it some more the patient is supposed to be given 400000 units. Thats the the dose for the patient. But youre gonna give that as a volume okay and so we look through find out that this 400.
Unis target to 1 meter. Of d5w. So this 1 meter.
D5w and extras. 5. Is your career or your large volume parent or thats the back.
Where you are going to put the drug in okay. So we dont need this quantity for any of the calculations in this particular example. We once we figure out how much volume.
Were gonna need we are going to put down volume into this bag this one liter bag okay and also it tells you that you have a viaduct contains five million units. So thats the total quantity of drug in your vial. It gives you how much volume to our does the volume of the diluent.
But the thing about the question is it actually gives you the final concentration. How do we know its units per volume units per ml all right so because we know the final concentration. All we need to do is basically set up a.
Proportion so what we will say is since the concentration is 500000 units per ml immediate 500000 units in each. Milliliter we want to give our patient 400000 units. Thats what we want to do so.
What will be the volume okay so once you know the final concentration of your reconstituted preparation anytime. Youre going to give it those you set up a proportion or some kind of ratio. This way all right so were going to solve for.
X which is. Our unknown and that should. Be basically 400000 units divided by the.
500000 is the x one ml youre 500000 units. So units cancel out all these evils cancel out and so 4. 5 is essentially.
08. Ml so our. Volume this is.
L our volume is going to basically be. 08. Ml okay so as you notice.
There was a lot going on here so many numbers and so much information. But just to recap the thing you want to look out for is anytime. You are calculating the dose just make sure you know what the final concentration is if its not given you have to calculate it right in this question it so happens that it was given to us as 500000 units per ml and so we set up this proportion to basically determine our unknown.
We solve for x. And we can do that we end up with zero point. 8.
Milli litres all right so now lets look at the third example. Where we are determining the volume of a diluent all right so. What you want to do is it tells us that the label instructions indicate to add three milliliters of sterile water for injection.
To one gram of cefazolin to give a final concentration of 18 milligrams per liter. How many milliliters of your sterile. Water for injection should be used to prepare the following order all right so once again you have quite a bit going on here and lets just clarify whats going to happen.
We weve been told that if we looked on the label or the vial label or look in the package. And said. Were supposed add three of the diluent that sterile water for injection to one gram.
And that should give us two eighty milligrams per ml. So thats given. But whats happening is you have an order from a physician and this physician wants to end up with a concentration of 250 milligrams per ml.
So if you remember my analogy with the kool aid this would be one time. Where maybe the kool aid was too sweet and so you wanted to dilute it same thing here the concentration. That is specified by the company that from later this product is to 80 milligrams.
But the physician wants something. Which is a little bit lower to 15 milligrams per ml. So we can simply add the recommended volume of the diluent all right so what do we do were going to do this in two steps.
The first thing. We are going to do is use the information that has been given. Which is the three ml one gram and 218 milligrams per ml to find out what the part of volume is and once we know that well go back and use our quantity and the new concentration.
Together with the volume of the part of all um determine the volume of dial. One. So its what i mean first of all we know that the quantity of drug divided by the final concentration is going to be equal to the volume of your diluent.
Plus. The powder volume okay and so what that means is we have a thousand milligrams. And this is from the 1 gram.
Divided by the two eighty milligrams per. Ml. And that should give us three ml.
Plus. The parable in which we do not know okay so gonna pull this up a little bit. We are done with that piece of information and if we solve for our unknown.
Youre going to end up with on this side of the equation is three point five seven equals three ml plus x. So the x is going to be equal to three point five seven minus three which is zero point five seven ml. So thats the powder volume.
So now that we know that we are going to make use of the new concentration. Okay. So the new concentration is such that you have your powder volume so your new concentration is going to be quantity of drug of a final concentration being equal to volume of your diluent.
Plus. The powder volume and so what we will have to do now is use the new final concentration. And now a new final concentration is 250.
Okay so we end up with a thousand milligrams divided by 250 milligrams per ml and that should be equal to what we do not know. Plus. The powder volume that we just figured out which is zero point five seven ml so on this side.
Well have four milliliters. We dont know what the volume of the diluent is but we know the power. The volume.
Okay so we can now solve for the new. Volume which would be x equals four minus. 057.
Ml and that would be equal to three point four three milliliters all right so the volume of diluent is going to be three point four three and if we compare to the original volume is high and we expect that well need more diluent to have a lower concentration. All right so let me just quickly go through the high points. Once again because this was fairly long.
The first thing you want to do is use the information given here to determine the powder volume. Thats what we use the three ml one gram and to 18 milligrams per ml form that gives us powder volume which would be basically the zero point five seven okay so that gives us this as the part of volume. And i will make use of that information together with the desired concentration.
Which was 250 milligrams to determine the volume of powder. And thats what happens down here. Okay.
So now we have the powered up volume and the powder volume for a particular drug would not change for a given forgiving drug alright. So we use that information again and this time. We make use of the new final concentration.
And and that gives us at the end of the day. The volume of dialogue wants to be three point four three mili liters. So i hope you found this video tutorial useful.
If you like that just click the like button subscribe to the channel be sure to check out our website wwwlaxcampscom. For more information about pharmaceutical calculations. And if you have any questions be sure to send me an email at prof m.
Dank wha at ow calculations calm. .
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