RECONSTITUTION, STABILITY AND STERILITY OF

INJECTABLE DRUGS

Presenter:

Deus D. Sinibagiye (Pharmacist)

PHARMACY DEPARTMENT
Presentation Outline
• Introduction

• Stability of different drugs after reconstitution

• Use and sterility of drugs packaged in Ampoules

• Drug Interaction
Introduction

• Drugs administered by injections are packaged in several ways.

• Those that deteriorate in solution are usually dispensed as

powders and reconstituted immediately before administration

• Stable drugs in solution are packaged in ampoules (single

dose/unit dose), bottles or vials in an aqueous, oily, emulsion and
suspension
• Many drugs used as sterile products, especially antibiotics are made as
dry powder form.

• It is extremely important that the correct diluents be selected and

appropriate calculations performed to ensure correct concentrations
and stability of finished product.

• Antibiotics in powder form generally have an extended shelf life;

however, once diluted most antibiotics lose their potency after a
relatively short period of time
Reconstitution
• Reconstitution is a process of combining dry form of a mixture
with a vehicle to achieve a usable state.

• It is also the process of diluting liquid concentrate to achieve a

usable state.
Diluent
• Diluent is a clinically inactive ingredient/liquid used to dilute or
reconstitute a medication.

• It is also used to convert a dry form of a substance to a liquid form.

• When reconstituting medications, read the directions to find out

which diluent needs to be used.

• Water or normal saline (NS) solution is often used to dilute
medicines and to liquefy dry powdered forms of medicines.

• Diluents are typically inserted with a syringe through the rubber

stopper of the medication vial for injectable drugs.

• For Oral or topical suspension, the diluent is measured properly,

added to the medication container and shaken really well to ensure
powders are dissolved properly
 Stability of drugs after reconstitution
DRUG NAME STABILITY AFTER STORAGE(°C) DILUENT
RECONSTITUTION
AMPICILLIN INJ 8HRS <25 NS/WFI

CLOXACILLIN INJ 24HRS/48HRS <25/(2-8) NS/WFI/D5W

BENZYL PENICILLIN INJ 24HRS/7DAYS <25/(2-8) NS/WFI/D5W

BENZATHINE PENICILLIN INJ. 24HRS/7DAYS <25/(2-8) NS/WFI/D5W

FORTIFIED PROCAIN PENICILLIN 24HRS/7DAYS <25/(2-8) NS/WFI/D5W/lidocain

(PPF) INJ

CEFTRIAXONE 3DAYS/10DAYS <25/(2-8) WFI/D5W/D10%

CEFOTAXIME INJ 12HRS/5-7DAYS <25/(2-8) WFI

MEROPENEN INJ 1HR <25 WFI/NS/D5%/D10%

HYDROCORTISONE INJ 4HRS <25 WFI/D5%/NS

CHLORAMPHENICOL INJ 24HRS <25 WFI

ARTESUNATE INJ 1HR <25 0.9%NS

Amoxicillin +Clavulanic acid injection
• AUGMENTIN intravenous should be given by slow intravenous
injection over a period of 3-4 minutes and within 20 minutes of
reconstitution.

• It may be injected directly into the vein or via a drip tube.

• To prepare AUGMENTIN for intravenous infusion, add without
delay 600mg reconstituted solution to 50mL normal saline infusion
or 1.2g reconstituted solution to 100mL normal saline infusion
fluid

• Infuse over 30-40 minutes and complete within the time stated.

• Satisfactory Augmentin concentrations are retained at 5°C and at

room temperature (25°C) in the recommended volumes of the
following infusion fluids.

• If reconstituted and maintained at room temperature, infusions

should be completed within the time stated
Intravenous Infusion Stability Period
250C
Water for Injection BP 4Hr

Sodium Chloride Intravenous Infusion B.P. (0.9% W/V) 4HR

Sodium Lactate Intravenous Infusion B.P. (M/6) 4HR

Compound Sodium Chloride Injection B.P.C 1959 (Ringer’s) 3HR

Compound Sodium Lactate Intravenous Infusion B.P 3HR

(Ringer – Lactate: Hartmann’s)
Potassium Chloride and Sodium Chloride Intravenous 3HR
Infusion B.P
• Any residual Augmentin solutions should be discarded.

• AUGMENTIN vials are not suitable for multi-dose use.

• AUGMENTIN intravenous is less stable in infusions containing glucose,

dextran or bicarbonate.

• Reconstituted solution should, therefore, not be added to such infusions

but may be injected into the drip tubing over a period of 3-4 minutes.
Ampicillin Stability
• I.V minimum volume: Concentration should not exceed 30mg/ml
due to concentration stability restrictions
Stability at Room Temp(250C)
DILUENT CONC STABILITY PERIOD

Sterile water for injection Up to 30mg/ml 8hrs

Isotonic sodium chloride Up to 30mg/ml 8hrs

5% dextrose in water 10 to 20mg/ml 1hr

5% dextrose in water Up to 2mg/ml 2hrs

5% dextrose in 0.45%NaCl Up to 2mg/ml 2hrs

Lactated Ringer’s solution Up to 30mg/ml 8hrs

Stability when Refrigerated (40C)
DILUENT CONC STABILITY

Sterile water for injection 30mg/ml 48hrs

Sterile water for injection Up to 20mg/ml 72hrs

Isotonic sodium chloride 30mg/ml 24hrs

Isotonic sodium chloride Up to 20mg/ml 48hrs

Lactated Ringer’s solution Up to 30mg/ml 24hrs

5% dextrose in water Up to 20mg/ml 1hr

Lactated Ringer’s solution Up to 10mg/ml 1hr

Meropenem Injection
• Meropenem for Injection to be used for bolus
intravenous injection should be constituted
with sterile Water for Injection (10mL per 500
mg Meropenem).

• This provides an approximate available

concentration of 50 mg/mL.

• Reconstituted solutions are both clear and

colourless to pale yellow
• Meropenem Injection to be used for
intravenous infusion may be directly
reconstituted with a compatible
infusion fluid and then further diluted
(50 to 200 mL) with the compatible
infusion fluid
• Shake reconstituted solution before use

• Standard aseptic technique should be employed during

reconstitution and administration
Ampoules

• An ampoule is a glass flask that contains a single dose of

medication for parenteral administration
• There is no way to prevent air bone
contamination of any unused portion
of medication after an ampule is
opened.

• If all the medications is not used, the

remainder must be discarded.

• All drugs which are in ampules when

are opened, they have to be used once
due to stability and sterility of the
drug.
Examples
• ATROPINE

• Calcium Gluconate IV

• Digoxin IV

• Dobutamine-within 6hrs

• Adrenaline

• Gentamicin

• Phenobarbitone

• Vitamin k-shortly after preparation

Interactions
• Some powdered drugs (injectable) tend to interact with some
diluent hence they are not suitable to be used together

• Ceftriaxone interact with ringer lactate(due to calcium) and form

precipitates which will affects the kidney and lungs of the patient

• Not recommended to be used together.

• Vancomycin, aminoglycosides, and fluconazole are incompatible with
ceftriaxone in admixtures.

• When any of these drugs are to be administered concomitantly with

ceftriaxone by intermittent intravenous infusion, it is recommended that
they be given sequentially, with thorough flushing of the intravenous lines
(with one of the compatible fluids) between the administrations
• Probenecid decreases the renal tubular secretion of amoxicillin

• Concomitant use with AUGMENTIN may result in increased and

prolonged blood levels of amoxicillin, but not of clavulanic acid

• Concomitant use of probenecid is not recommended

• Concomitant use of allopurinol during treatment with amoxicillin

can increase the likelihood of allergic skin reactions
• A clinically significant reduction in serum valproic acid
concentration has been reported in patients receiving carbapenem
antibiotics resulting a 60-100% decrease valproic acid levels in
about two days

• The concomitant use of meropenem and valproic acid/sodium

valproate/valpromide is not recommended.

Probenecid competes with meropenem for active tubular secretion and thus
inhibits the renal excretion of meropenem with the effect of increasing the
elimination half-life and plasma concentration of meropenem
Clinical Relevance
• Reconstituted medications for multidose use are the one exception to
the rule, “Never give a medication prepared by someone else”

• The exception may be made only if the label is clearly marked with
all the requires data

• Reconstituted medications with labels that are annotated with all

the required data must be discarded to avoid giving an ineffective
drug or a spoiled liquid
• Because of the cost and short shelf life of reconstituted
medications, it is appropriate that the nurse review the patient’s
records and recent orders to be sure that the medication order has
not expired before preparing the medication
References

• Neonatal Parenteral medications stability Manual King Abdullah

University Hospital

• New Zealand Data Sheet of Meropenem

• hydrocortisone sodium succinate for injection, USP

• Lippincot photo atlas of medication administration
THANK YOU