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Category Antiviral.

      Idoxuridine contains not less than 98.0 per cent and not more than 101.0 per cent of C₉H₁₁IN₂O₅, calculated on the dried basis.

Description White or almost white, crystalline powder

Solubility Slightly soluble in water and in ethanol; practically insoluble in ether.

Stability Aqueous solutions are most stable when the pH is adjusted to between 2º and 6º; they should be freshly prepared and kept in a refrigerator. Some decomposition products are more toxic than idoxuridine and reduce its antiviral activity

Warning

      1. It should be used with caution in conditions when there is deep ulceration involving the stromal layers of the cornea, as delayed healing has resulted in corneal perforation. Prolonged topical use should be avoided.

      2. It may cause hypersensitivity i.e. itching, redness, swelling, pain, or other signs of irritation not present before therapy, allergic reactions, corneal clouding, or punctate defects in the corneal epithelium; or increase sensitivity of eyes to light. Prolonged use may cause follicular conjunctivitis, punctal occlusion or conjunctival scarring.

      3. Idoxuridine has been reported to be cytotoxic and potentially mutagenic, carcinogenic and teratogenic; its systemic use is thus not recommended.

      4. Boric acid preparations should not be applied to the eye in patients also receiving ocular preparations of idoxuridine as irritation ensues.

      5. Since safety for topical use in pregnancy or in the nursing mothers has not been established, risk-benefit should be considered before use.

Precaution

      1. Periodic ophthalmologic, including slit-lamp, examinations are recommended during therapy.

      2. The medication should be continued for 5 to 7 days more after the lesion is apparently healed, otherwise recurrence may occur.

Additional information

1. Patients sensitive to iodine or iodine-containing preparations may be sensitive to this medication also.

2. Corticosteroids can accelerate the spread of viral infections and are usually contra-indicated in superficial herpes simplex virus keratitis. However, steroids may be used concurrently with idoxuridine in the treatment of herpes simplex infections with stromal lesions, corneal edema, or iritis. Prolonged administration with corticosteroids may be required. Idoxuridine should be continued for a few days after the steroid has been discontinued. 

Packaging and storage Idoxuridine shall be kept in well-closed containers, protected from light.

Identification

      A. The infrared absorption spectrum is concordant with the spectrum obtained from Idoxuridine RS (Appendix 2.1) or with the reference spectrum of Idoxuridine.

      B. Examine the chromatograms obtained in the test for Related substances: the principal spot in the chromatogram obtained from Test solution (b) is similar in position and size to the principal spot in the chromatogram obtained from Reference solution (c).

      C. Heat 5 mg in a test-tube over a naked flame: violet vapour is evolved.

      D. Disperse 2 mg in 1 ml of water and add 2 ml of diphenylamine TS. Heat in a water-bath for 10 minutes: a persistent light-blue colour develops.

pH 5.5 to 6.5, in a 0.10 per cent w/v solution (Appendix 4.11).

Loss on drying Not more than 1.0 per cent w/w after drying at 60º at a pressure not exceeding 2.7 kPa (about 20 Torr) over phosphorus pentoxide desiccant for 2 hours (Appendix 4.15).

Specific rotation +28º to +32º, calculated on the dried basis, determined in a 1.0 per cent w/v solution in 1 M sodium hydroxide (Appendix 4.8).

Sulfated ash Not more than 0.1 per cent w/v (Appendix 5.3).

Related substances Carry out the test as described in the “Thin-layer Chromatography” (Appendix 3.1), using silica gel  GF254 as the coating substance and a mixture of 10 volumes of strong ammonia solution, 40 volumes of chloroform and 50 volumes of 2-propanol as the mobile phase.

      Solvent mixture Mix 1 volume of strong ammonia solution and 5 volumes of methanol.

      Test solution (a) Dissolve 200 mg of the test substance and dilute to 5 ml with Solvent mixture.

      Test solution (b) Dilute 1.0 ml of Test solution (a) to 10 ml with Solvent mixture.

      Reference solution (a) Dissolve 20 mg of 5-iodouracil, 20 mg of 2’-deoxyuridine and 20 mg of 5-bromo-2’- deoxyuridine and dilute to 100 ml with Solvent mixture.

      Reference solution (b) Dissolve 200 mg of the test substance in 5.0 ml of Reference solution (a).

      Reference solution (c) Dissolve 20 mg of Idoxuridine RS and dilute to 5 ml with Solvent mixture.

      Reference solution (d) Dilute 1.0 ml of Test solution (b) to 20.0 ml with Solvent mixture.

      Procedure Apply separately to the plate 5 μl of each solution. After removal of the plate, allow it to dry in a current of cold air and examine in ultraviolet light (254 nm). In the chromatogram obtained from Test solution (a): any spots corresponding to 5-iodouracil, 2’-deoxyuridine and 5-bromo-2’-deoxyuridine are not more intense than the corresponding spots in the chromatogram obtained from Reference solution (a) (0.5 per cent); any spot, apart from the principal spot and the spots corresponding to 5-iodouracil, 2’- deoxyuridine and 5-bromo-2’-deoxyuridine, is not more intense than the spot in the chromatogram obtained from Reference solution (d) (0.5 per cent). The test is not valid unless the chromatogram obtained from Reference solution (b) shows four clearly separated spots.

Inorganic iodide Not more than 0.1 per cent w/w. Dissolve 250 mg of the test substance in 25 ml of 0.1 M sodium hydroxide, add 5 ml of dilute hydrochloric acid and dilute to 50 ml with water. Allow to stand for 10 minutes and filter. To 25.0 ml of the filtrate, add 5 ml of hydrogen peroxide TS (10 volumes) and extract with 10.0 ml of chloroform. Any pink colour in the organic layer is not more intense than that in a standard prepared at the same time in the same manner using 1.0 ml of a 0.033 per cent w/v solution of potassium iodide instead of the test substance.

Assay Dissolve about 300 mg of Idoxuridine, accurately weighed, in 20 ml of dimethylformamide. Titrate with 0.1 M tetrabutylammonium hydroxide VS, determining the end-point potentiometrically (Appendix 6.1). Perform a blank determination, and make any necessary correction. Each ml of 0.1 M tetrabutylammonium hydroxide is equivalent to 35.41 mg of C₉H₁₁IN₂O₅.