Stability of Dicloxacillin Sodium

in Elastomeric infusion
pumps

J. Nejatbakhsh, H. Omestad and H. Jespersen

Hospital Pharmacy Aarhus,
Aarhus University Hospital, Denmark
Email: yousneja@rm.dk

Background
The ambition for the Hospital Pharmacy Aarhus is to deliver drugs ready
to use. The drugs have to be quality assured according to microbiology
and stability.
Several published studies demonstrate advantages of using portable
elastomeric pumps for outpatient parenteral antimicrobial therapy. An
increase in mobility, a decrease in inpatient days and a decrease in
nosocomial infections are some of the advantages. At Department of
Orthopaedics, Aarhus University Hospital, the most common parenteral
agent for treating osteomyelitis is dicloxacillin 2 g three times a day for
2 weeks. Using portable elastomeric pumps for this treatment gives the
patients opportunity to stay at home most of the time. Data on the
stability of dicloxacillin (see figure 1) in elastomeric pumps was not
available. Therefore the pharmacy initiated a study to investigate the
stability prole of dicloxacillin sodium 10 mg/ml in sodium chloride 0.9%
in elastomeric infusion pumps.
Figure 2: HPLC chromatogram of dicloxacillin sodium standard

CI

O
O

NH
CH3

CH3 , H2O

CI

CO2Na

CH3

Figure 1: Dicloxacillin sodium structure

Method
Three batches of dicloxacillin sodium (Diclocil, Bristol-Myers Squibb) 10
mg/ml in sodium chloride 0.9% solution in elastomeric infusion pumps
(Intermate, Baxter) were prepared aseptically at the Hospital Pharmacy
Aarhus.
The dicloxacillin concentration was assayed by HPLC. HPLC analysis was
performed by using an Elite LaChrom system employing a DAD detector.
Each sample and standard was injected in duplicate. The HPLC method
was validated in accordance to detection limit, linearity r2 = 0,999 and
precision RSD < 1%. The detection limit was dened as three times the
baseline noise, being 1.5 g/ml. During the development of the method
a dicloxacillin solution was stressed by temperature and afterwards
analyzed by HPLC to determine the degradation prole of dicloxacillin,
see gure 2 and 3.
Further more pH and particle content were measured. The microbiological
status was examined by Test for Sterility and Container Closure
Integrity Test.
The quantitative content and pH of the solution were measured after 0,
22, 70, 94 and 167 hours of storage at 53C. The samples were kept at
room temperature for at least one hour before they were analyzed.

Figure 3: HPLC chromatogram of decomposed dicloxacillin sodium. Peaks from

the decomposition products do not interfere with the dicloxacillin peak
Tabel 1: Measured concentrations of dicloxacillin sodium
Time of
analysis (h)

Sample concentration (% of initial concentration )

Batch 1

Batch 2

Batch 3

(9,46 0,13 mg/ml)

100

(9,76 0,09 mg/ml)

100

(9,53 0,05 mg/ml)

100

22

101,59

101,54

101,68

70

101,8

100,72

100,63

94

101,8

100,41

100,21

167

101,59

99,9

100,94

Intermate
Infusion System

Results and Discussion

Conclusion
Dicloxacillin sodium 10 mg/ml in sodium
chloride 0.9% in elastomeric infusion pumps remained
stable during 167 hours at 53C followed by 1 hour at
room temperature, protected from direct sunlight.
The hospital pharmacy now offers to prepare
dicloxacillin sodium 10 mg/ml in sodium chloride 0.9% in
elastomeric infusion pumps.

Layout: Department of Communication, Aarhus University Hospital, Skejby TT0210LB

The content of dicloxacillin practically remained stable during the 167

hours of storage at 53C followed by 1 hour at room temperature, see
table 1. It was not possible to detect any degradation products during
the test period. A slight decrease in pH was observed, probably as a
result of hydrolysis of the -lactam ring in dicloxacillin.
No growth of micro-organisms occurred during the test period.