Itraconazole

METHOD OF PREPARATION

Note: This preparation should be done in a laminar airflow hood in a cleanroom or via isolation barrier technology by a validated aseptic compounding pharmacist using strict aseptic technique.

1. Calculate the required quantity of each ingredient for the total amount to be prepared.

2. Accurately weigh and/or measure each ingredient.

3. Add the propylene glycol, hydrochloric acid to about 90% of the calculated quantity of sodium chloride irrigation and adjust the pH to 4.5.

4. Sterile filter the solution into a suitable sterile container.

5. Add the intraconazole injection and mix well.

6. Add sufficient sodium chloride injection to volume and mix well.

7. Package and label.

PACKAGING

Package in tight, light-resistant containers.1

LABELING

Keep out of reach of children. Use only as directed.

STABILITY

If no sterility testing is done, a beyond-use date of 24 hours at room temperature, 3 days at refrigerated temperature or 45 days at

USE

Intraconaxole nasal irrigation is used for fungal infections of the nasal and sinus cavities.

QUALITY CONTROL

Quality-control assessment can include weight/volume, physical observation, pH, specific gravity, osmolality, assay, color, clarity, paniculate matter, sterility and pyrogenicity.2,3

DISCUSSION

Itraconazole is not water-soluble so it presents many challenges to formulate as an acceptable nasal irrigation solution. Some have used capsules as the source of the drug while others have used the injection. The advantage to using the injection is that it is a sterile solution. The diluting liquid can be prepared, sterile-filtered and then used to dilute the injection if desired. This injection may precipitate out of solution over time but that should not adversely affect the efficacy of the drug, as this is a physical phenomenon.

Uraconazole (C^sub 35^H^sub 38^Cl^sub 2^N^sub 8^O^sub 4^, MW 705.63, Sporanox) occurs as a white-to-slightly yellowish powder. It is insoluble in water and very slightly soluble in alcohols. It has a pK^sub a^ of 3.70. Itraconazole injection is a sterile pyrogen-free clear, colorless-to-slightly yellow solution for intravenous infusion. Each mL contains 10 mg of itraconaxole, solubilized by hydroxypropyl-β-cyclodextrin (400 mg) as a molecular inclusion complex, with 3.8 µL hydrochloric acid, 25 µL propylene glycol and sodium hydroxide for pH adjustment to 4.5, in water for injection. Each 25-mL ampule contains 250 mg itraconazole packaged with a plastic bag of 0.9% sodium chloride injection in which it is diluted prior to infusion.1,4

Propylene glycol (C^sub 3^H^sub 8^O^sub 2^, MW 76.09) occurs as a clear, colorless, viscous, practically odorless liquid with a sweet taste, somewhat resembling glycerin. It miscible with acetone, 95% cthanol, glycerin and water.5

Hydrochloric acid (HCl, MW 36.46) occurs as a clear, colorless, fuming aqueous solution of hydrogen chloride that has a pungent odor. Concentrated hydrochloric acid is 36.5-38.0% w/w concentration. It has a specific gravity of 1.18 g/cm^sup 3^, is miscible with water and is soluble in ethanol. Hydrochloric acid should be stored in well-closed glass or other inert containers.6

Sodium hydroxide (NaOH, MW 40.00, caustic soda, soda lye) occurs as dry, very deliquescent, white or almost-white sticks, pellets or fused masses that are hard and brittle. It is strongly alkaline and corrosive and rapidly absorbs moisture and carbon dioxide when it is exposed to air. It is soluble 1 g in 1 mL of water and is freely soluble in alcohol. It should be stored in airtight, nonmetallic containers.7

Sodium chloride irrigation is Sodium Chloride Injection

USP that has been suitably packaged, and it contains no antimicrobial agents.1

REFERENCES

1. US Pharmacopeial Convention, Inc. United States Pharmacopeia 27-National Formulary 22. Rockville, MD: US Pharmacopeial Convention, Inc.; 2004: 1701, 1950, 2345-2349.

2. Allen LV Jr. Standard operating procedure for particulate testing for sterile products. IJPC 1998; 2: 78.

3. Allen LV Jr. Standard operating procedure: Quality assessment for injectable solutions. IJPC 1999; 3: 406-407.

4. Trissel LA. Handbook on injectable Drugs. 12 ed. Bethesda, MD: American Society of Health-System Pharmacists; 2003: 818-819.

5. Weller PJ. Propylene glycol. In: Rowe RC, Sheskey PJ, Weller PJ, eds. Handbook of Pharmaceutical Excipients. 4th ed. Washington, DC: American Pharmaceutical Association; 2003: 521-523.

6. Weller PJ. Hydrochloric Acid. In: Kibbe AH, ed. Handbook of Pharmaceutical Excipients. 3rd ed. Washington, DC: American Pharmaceutical Association; 2000: 238-239.

7. Reynolds JEF, ed. MARTINDALE: The Extra Pharmacopeia. 30 ed. London: Pharmaceutical Press; 1993: 1415.

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