How To Prepare Fortified Eye Drops

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To Prepare Fortified eye drops means to increase the effectiveness of eye drops by additional ingredients. Fortified ophthalmic solutions are commonly used in severe keratitis for better corneal penetrations. These kinds of fortified ophthalmic preparations are not commercially available. The meaning of fortified means adding a parenteral antimicrobial to a commercially available product to make a higher or non-available concentration.

Things to know before preparing fortified eye drops

Before Preparing fortified antimicrobial eye drops please remember the following instructions.
  • The Fortified eye drop making process should be only done by an eye care practitioners or pharmacist inside a sterile chamber or an Operation Theater where contamination can prevent. Prepare it under sterile condition.
  • Always use a sterile disposable syringe while preparing the fortified antimicrobial eye drops. After preparing the drop please mention the preparation date and expiry date label on the eye drop vial.
  • Please give the proper instruction to the patient about the frequency of using eye drops and storage instruction. Drops that are to be refrigerated at 4degree Celcius can be kept on the refrigerator door. (2)

 

Commonly used fortified eye drops preparation

Fortified Gentamicin (14mg/ml)

To prepare fortified Gentamicin we need, Gentamicin Ophthalmic Solution 0.3%  and Gentamicin IV injection 40mg/ml and a sterile disposable syringe. With a syringe, Add 2ml (80mg) Gentamicin Injection directly into a 5 ml Gentamicin eye drop 0.3% (15mg).
After mixing it total of 7ml preparation of Gentamicin ophthalmic solution (fortified) will be formed about the concentration of 13.6mg/ml.
Shelf Life: 1 week in the refrigerator at 4 degrees C
Fortified Gentamicin Ophthalmic Solution 14mg

Fortified Tobramycin 

To prepare fortified Tobramycin eye drop we need, Tobramycin Ophthalmic Solution 0.3%  and Tobramycin IV injection 40 mg/ml and a sterile disposable syringe. With a syringe, Add 2ml (80mg) Gentamicin Injection directly into a 5 ml Tobramycin eye drop 0.3% (15mg).
After mixing it total of 7ml preparation will be formed about the concentration of 13.6mg/ml.
Shelf Life: 1 week in the refrigerator at 4 degrees C

Fortified Amikacin 40 mg/ml

The intravenous formulation of Amikacin can be used (80 mg/2 cc ampules). (3)

Fortified Cefazolin (50 mg/ml)

To make fortified cefazoline eye drop, first of all, take 250mg dry cefazolin for injection and mix it with 5 ml sterile distilled water for injection. If you have 500mg Cefazolin, add 10 ml sterile distilled water for injection to make 50mg/ml concentrations.

Shelf life: At Normal Room temperature usually discards it after 3 days and 7  days If refrigerated at 4 degrees C.

Fortified Vancomycin

Vancomycin 15 mg/ml, Vancomycin 25 mg/ml, or Vancomycin 50 mg/ml

First of taking a 500-mg vial of vancomycin and follow these steps by AAO (3)

  1. To prepare Vancomycin Ophthalmic solution of 15 mg/ml concentration,  Add 33 ml of 0.9% sodium chloride for injection USP (no preservatives) or artificial tears
  2. Add 20 ml of 0.9% sodium chloride for injection USP (no preservatives) or artificial tears to produce a
    solution of 25 mg/ml.
  3. Add 10 ml of 0.9% sodium chloride for injection USP (no preservatives) or artificial tears to produce a
    solution of 50 mg/ml.

Refrigerate and shake well before installation.

 

Old Methods to Prepare Vancomycin 50 mg/ml

Mix 500mg Vancomycin powder with 10 ml sterile water for injection. Its concentration will be 50 mg/ml, which Expires in 4 days if refrigerated.

Fortified Amphotericin-B (1.5mg/ml) 0.15%

Mix 10 ml of sterile water for injection in 50 mg of Amphotericin-B powder for Injection. This will give a 5mg/ml solution. After that on the second steps take 3 ml (15mg) from the above solution and mix 7 ml of sterile water. This will give you 15mg/10ml i.e. 1.5mg/ml i.e. 0.15%

Keep this solution in a refrigerator. Drops are clear yellow in colour if they turn milky then discard them.

 

Another New Method (Mixing with Artificial Tears)

Add 10 ml distilled or sterile water for injection to parenteral 50mg of amphotericin B powder for injection. Draw 3 ml of this and add to 7ml of artificial tears eye drops, so it will give 1.5mg/10 ml which is Fortified Amphotericin-B Eye Drop 0.15% concentration.

Shelf life: 7 days in a refrigerator at 4 Degree Celsius and 4 days at room temperature.

 

Topical voriconazole eyedrops (1%)

Nowadays brand name Vozole composition Voriconazole 1% eye drops manufactured by Aurolab India is available in Nepal. It contains 30 mg sterile lyophilized dry Voriconazole powder. To get 1% (10 mg/ml) solution, this powder has to be reconstituted with 3 ml of Water for Injection.

 

Another Method

Voriconazole powder (200 mg) is reconstituted with 19 ml of sterile water for injections in order to obtain 20ml of a 10-mg/ml voriconazole solution: Voriconazole eyedrops (1%) (5)
Storage: Refrigerate at 4°C and shake well before installation

 

Trimethoprim/sulfamethoxazole

A 16-mg/ml / 80-mg/ml commercial preparation can be used.

 

Colistin 0.19%

Intravenous colistimethate sodium powder 1 million IU/75 mg to 10 ml of distilled water to produce 7.5 mg/ml (0.75%). Add 1 ml of this solution to 3 ml of distilled water. So the final preparation will be 0.19%.

 

Disclaimer: This article is for educational purpose only. The shelf life of drugs may vary with practitioners view. Consult with an Ophthalmologist for preparation and shelf life advice. Do not take these articles guides for the treatment. 
References
1. Chiquet C, Romanet JP. Prescrire les collyres fortifiés [Prescribing fortified eye drops]. J Fr Ophtalmol. 2007 Apr;30(4):423-30. French. doi: 10.1016/s0181-5512(07)89618-5. PMID: 17486040.
2. Nixon HK. Preparation of fortified antimicrobial eye drops. Kerala J Ophthalmol [serial online] 2018 [cited 2021 May 27];30:152-4. Available from: http://www.kjophthal.com/text.asp?2018/30/2/152/239986
3. American Academy of Ophthalmology. Available from https://www.aao.org/preferred-practice-pattern/bacterial-keratitis-ppp-2018
4. Aurolab India voriconazole eye drops. Available from https://www.aurolab.com/voriconazoleeyedrops.asp
5. Dupuis A, Tournier N, Le Moal G, Venisse N. Preparation and stability of voriconazole eye drop solution. Antimicrob Agents Chemother. 2009 Feb;53(2):798-9. doi: 10.1128/AAC.01126-08. Epub 2008 Nov 10. PMID: 19001119; PMCID: PMC2630666.

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