Question
Posted on: March 6 2013Problem with miconazole in eye drops.
We have had a pati ë nt with mold keratitis which was treated with itraconazole eye drops. Apparently there was a problem with the solubility of the product, because the cornea of the Pati ë NT got a white batter, which after stopping the treatment disappeared badly slowly. There is very little concrete information on such products; And in the Netherlands if it is not in an official compendium, it is not possible to get such preparations. Can you help me with formulations?
Answer
One finds mainly formulations for ear drops because given the insolubility in water of both miconazole and Miconazole nitrate, the leespace in terms of solvents is slightly wider as for eye drops. The following formulations can be used for eye drops:
Rinse a tarred mortar with stamper with Isopropanol 70% and allow to dry. Apply the micoinazole in the mortar and add 5 ml of Cremophor EL. Mix into a homogeneous paste and then gradually add the remaining Cremophor EL. Edit all Agglomerates and homogenize. Add lactic acid and mix. Take a vial of 100 ml of sterile water and apply about 30 ml in the mortar. Homogenize the mixture and place mortar and pestle on the balance. Bring on weight with the residual sterilized water.
Check the pH (= 3.7) and filter 10 ml through a 0.22 µ m sterilized filtration in a sterilized eye dropper vials. Repeat this operation until the whole solution is filled.
FORMULATION I
R/Miconazole 500 mgcompound Benzalkonium chloride solution:
cremophor EL 12 g
benzalkonium chloride solution 10 g
NaCl 700 mg
after Monohydrogen phosphate 12 Aqua 250 mg
Water for injections up to 100 g
Benzalkonium chloride 88 mgTHIS SOLUTION can be Sterilized by autoclaving and preserved for subsequent preparations.
Di Na EDTA 2 aq 1 g
water for injections up to 100 g
Preparation:
after preparing the solution WITH MICONAZOLE, it is filtered on a sterilized membrane filter Pori ë n diameter 0.25 micrometer in pre-sterilised 10 ml eyedropper vials.
Note:
When used, ë the patients should be monitored closely to determine whether or not irritation occurs and whether the eye drops are well tolerated. After all, there is a tensio active in this formulation. Tensio-active substances are not common in eye drops but here this product is absolutely necessary for putting in solution.
FORMULATION II
R/miconazole 1gPreparation:
Cremphor EL 12ml
Lactic acid 44% 1ml
water for inject. Up to 100ml
Rinse a tarred mortar with stamper with Isopropanol 70% and allow to dry. Apply the micoinazole in the mortar and add 5 ml of Cremophor EL. Mix into a homogeneous paste and then gradually add the remaining Cremophor EL. Edit all Agglomerates and homogenize. Add lactic acid and mix. Take a vial of 100 ml of sterile water and apply about 30 ml in the mortar. Homogenize the mixture and place mortar and pestle on the balance. Bring on weight with the residual sterilized water.
Check the pH (= 3.7) and filter 10 ml through a 0.22 µ m sterilized filtration in a sterilized eye dropper vials. Repeat this operation until the whole solution is filled.