Reconstitution of Powders
A number of drugs are unstable in an aqueous environment, thus requiring packaging, storage, and shipping in a powder or lyophilized state to keep the product stable during its shelf life. These drugs will then have to be reconstituted, or mixed with sterile water for injection, or other sterile diluents such as normal saline at the time of administration. The most important factor to consider in reconstitution is the contribution of the dry powder to the volume of the reconstituted preparation. For example, Table B illustrates that if a vial of ampicillin for intravenous use has a very small amount of ampicillin (250 mg); it will be unlikely that the drug contributes significantly to the volume once reconstituted. Therefore, the concentration of the constituted drug in the vial will simply be the amount of drug in the vial divided by the volume of diluent. As seen in the table below, the concentration of the resulting solution is 250 mg/ 5 ml, which is 50 mg/ml. However, if the amount of ampicillin is large enough (2g); it will contribute to the volume once reconstituted. So in this case the concentration of the constituted drug is not equal to the amount of drug in the vial divided by the volume of the diluent. As seen in the table below, the concentration of the resulting solution is not 2 g/ 10 ml ( 200 mg/ml), it is less than that since the powder itself occupies volume which is 1 ml in this case.
Table B: Reconstitution of Ampicillin for Injection for Intravenous Use
Vial Size |
Diluent Added |
Approximate Withdrawable Volume |
Approximate Concentration Per ml |
|---|---|---|---|
| 250 mg | 5 ml | 5 ml | 50 mg |
| 500 mg | 5 ml | 5 ml | 100 mg |
| 1 g | 7.4 ml | 8 ml | 125 mg |
| 2 g | 10 ml | 11 ml | 180 mg |
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Solved Problem: A vial of 1 gram vancomycin when diluted with 20 ml of sterile water for injection results in a drug concentration of 50 mg/ml. Calculate the volume of injection occupied by the vancomycin powder. Approach: Divide the total amount of drug by the total volume of the diluent. Compare it to the final drug concentration achieved.
$$ { 1000 \ mg \over 20 \ ml } = {50 \ mg \over ml } $$ 1000mg/20 ml is equivalent to the final concentration of 50 mg/ml, thus the volume of injection occupied by the drug is negligible. Answer: Negligible |
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Solved Problem: Diluting 1 gram of ceftazidime with 3 ml of sterile water for injection results in a solution with ceftazidime concentration of 280 mg/ml. Calculate the volume of injection occupied by ceftazidime powder. Approach: If 280 mg is present in 1ml of solution, set up a proportion to calculate the volume for 1000 mg
$$ {280 mg \over ml} = {1000 mg \over x \ ml}; \ x = {3.6 \ ml \ (final \ volume)} $$ $$ { Final \ volume } = { 3.6 \ ml; } {\ Diluent \ volume \ } = { \ 3 \ ml } $$ $$ Volume \ occupied \ by \ the \ dry \ powder = {Final \ volume - Diluent \ volume } $$ $$ Volume \ occupied \ by \ the \ dry \ powder = {3.6 \ ml - 3 \ ml } = 0.6 \ ml $$ Answer: 0.6 ml |
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Solved Problem: A pharmacist receives a medication order of cefotaxime 1 gram to be added to 100 ml of D5W. The directions on the 2 gram vial state reconstitute with 10 ml of sterile water to yield 180 mg/ml of cefotaxime. How many milliliters of the reconstituted solution must be withdrawn and added to D5W? Approach: Use ratio and proportion to calculate the volume of the reconstituted solution. $$ { 180 \ mg \over 1 \ ml } = {1000 \ mg \over x \ ml } {; \ x } = 5.6 \ ml$$ Answer: 5.6 ml |
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Solved Problem: A hospital pharmacist received the following order for a patient: Medication order: 1500 mg Ampicillin IV q 6 hr
Approach: set up a proportion to calculate ml of the reconstituted solution equivalent to 1500 mg of Ampicillin. $$ { 250 \ mg \over ml } = { 1500 \ mg \over x \ ml } {; \ x } = {6 \ ml}$$ Answer: 6 ml b) What is the infusion rate in ml/hr? Approach: Use the infusion rate formula to calculate infusion rate $$ Infusion \ Rate = { Volume \ of \ infusion \ (ml) \over Time \ (min \ or \ hr )} $$ $$ Infusion \ Rate (ml/hr) = {100 + 6 \ ml \over 30 \ min } { \times } { 60 \ min \over hr } $$ Answer: 212 ml/hr c) With a drop factor of 20 drops per milliliter, calculate the infusion rate in drops per minute. Approach: Use the drip rate formula to calculate infusion rate in drops/min. $$ Drip \ rate = { Drop \ Factor \times Infusion \ Rate } $$ $$ Drip \ rate = {20} { gtt \over ml } { \times } {106 \ ml \over 30 \ min} \ = \ 70.6 \ = \ 71 \ drops $$ Answer: 71 drops/min |