Download 16 June 2016 Reconstitution Stability andSterility of injectable drugs.

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
RECONSTITUTION
STORAGE(°C)
DILUENT
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
(PPF) INJ
24HRS/7DAYS
<25/(2-8)
NS/WFI/D5W/lidocain
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
(Ringer – Lactate: Hartmann’s)
3HR
Potassium Chloride and Sodium Chloride Intravenous
Infusion B.P
3HR
• 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
reconstitution and administration
should
be
employed
during
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