[e-drug] RFI: frusemide oral liquid from injection (or tablet?) for a child

e-drug
1

E-DRUG: RFI: frusemide oral liquid from injection (or tablet?) for a child
--------------------------------------------------------------------------

Dear e-druggers,

I am the chief pharmacist at King Faisal Hospital
Kigali, Rwanda. This is a tertiary level hospital.

I need to extemporaneously prepare an oral solution
(or supension?) of frusemide 1mg/ml for a child
currently admitted in the hospital. This drug has
stability issues and physicochemical properties which
make preparation of an oral solution challenging.

Any ideas on how to go about it? I invite your
suggestions. Thanks in anticipation.

Evans Sagwa
Chief Pharmacist
King Faisal Hospital-Kigali, Rwanda
Tel +250588888 ext 1316
esagwa@yahoo.com

2

E-DRUG: RFI: frusemide oral liquid from injection (or tablet?)(2)
----------------------------------------------------------------

Dear Sagwa,
   
We use Emixture tool in our hospital to guide in preparation of extemporaneously medications. Its comprehensive but some of the materials recommended may not be readily available. You may contact the providers at
emixt@pharminfotech.co.nz or http://www.pharminfotech.co.nz.
  
See info on frusemide preparation below.

Frusemide Oral liquids are commercially available world-wide and all attempts should be made to obtain them.
This information is included for use only in emergencies when there are supply problems.

Frusemide is practically insoluble in water. The injection (frusemide sodium) is prepared with the aid of sodium hydroxide and has a pH of 8 - 9.3. Frusemide undergoes hydrolysis in acidic media and is most stable in alkaline solution.1,2 Tablets and solutions are light sensitive.

NOTES

Recommendations
    
If practical, disperse or crush the tablet (or the fraction which corresponds to the dose) in a small volume of liquid immediately prior to administration.

Give the injection orally. If dilution is necessary use sterile water and maintain the pH at 8 - 9. Refrigerate, protect from light. Expiry date: 7 days maximum.

In theory mixtures from tablets can be prepared. Adjustment to pH 8 - 9 with sodium hydroxide should produce a solution of frusemide sodium.
Ethanol increases, whereas sugar solutions decrease, the stability of frusemide in aqueous systems.1 The best choice of vehicle is a mixture of sorbitol and water, preferably with 5 - 10% ethanol. Parabens are compatible with frusemide solutions.1

REFERENCES

Ghanekar A.G., Das Gupta V., Gibbs C.W. Stability of furosemide in aqueous systems.
J Pharm Sci 1978; 67 (6): 808-811.

Addicks W. Furosemide. In: Connors K.A., Amidon G.L., Stella V.J.
Chemical Stability of Pharmaceuticals. New York: John Wiley, 1986: 474-77.

Regards
   
Dr Patrick Boruett
The Mater Hospital
Nairobi, Kenya

3

E-DRUG: RFI: frusemide oral liquid from injection (or tablet?) (4)
-----------------------------------------------------------------
[OK, thanks for the suggestions; discussion closed. I hope the little child benefitted from these responses? Wilbert, moderator]

Dear Mr. Evans,

In the Netherlands we have two accepted ways of preparing a liquid furosemide oral formulation (Source: National Pharmacist Lab), one for an oral suspension and one for an oral solution.

In both cases a lot of additional chemicals are necessairy for the
preparation. I can very well imagine that your pharmacy doesn't have chemicals like trometamol, Bentonit, etc, etc.....

As far as I know, the only problem with furosemide in a fluid is it's
solubillity, which is quite low in a Ph-neutral- or acidic-environment.

Most generic versions of furosemide injectables ONLY contain furosemidum
(base, NOT HCl) together with sodiumchloride (for the proper osmolarity) and
sodiumhydroxide (to provide a basic environment) and aqua injectabile. The
final product should have a pH of about 7.4.

Most generic versions of furosemide tablets contain furosemide (base) and m.c. cellolose, lactosemonohydrate, starch and magnesiumstearate.

In my opinion the easiest way to make a ad-hoc preparation of a liquid oral
formulation in your case be to simply use the furosemide injection as a
source. You can simply dillute this solution for injection to a 1 mg/ml oral
solution by dilluting it with aqua injectabile. But please make sure that the final product has an pH of about 7.4. If not, the furosemide might
precipitate. You can do this by measuring the pH and adding NaOH-solution
until you reach the requested pH.

Please note that you have to check the injections if there are no other
chemicals present in the solution, this might completelly change the preparation.

Please also note that this solution for oral use is NOT conserved and can
there only be used for a maximum period of 1 month.

If anybody is interested in receiving 2 alternate German ways of preparation, which are rather difficult and need a lot of additional chemicals, please let me know.

Good luck and please let us know what your findings are.

Best regards,

Mechiel Weits, Msc. Pharm,
consultant in essential medicines issues
PharmacationEdu,
The Netherlands
m_weits@hotmail.com