Formulation in Pharmacy Practice   2nd Edition

ITRACONAZOLE
 
 
Itraconazole is insoluble in water and very slightly soluble in alcohols.
Oral liquids have been prepared extemporaneously but studies have shown that the absorption of itraconazole from these preparations is highly variable, and in general the bioavailability is much lower than that from the capsules.2,3  An oral solution is commercially available in some countries and this is specially formulated with cyclodextrins.  Manufacturer's literature should be consulted for information about the absorption characteristics of the commercially available solution compared with capsules.
If an oral liquid preparation of itraconazole is required the commercially available liquid should be used whenever possible.
The following information is provided as a guide but the possibility of altered bioavailability should be considered.

Formula 1

Itraconazole Suspension 40mg per mL
 
Itraconazole capsules  100mg 24   
Ethanol 95% mL
Syrup to   60  mL
 
Empty the beads from the capsules into a glass mortar and add the 95% ethanol.  Allow to stand for several minutes until the beads have softened.  Grind to a paste, and then eventually to a fine powder once the ethanol has evaporated.  Add the syrup in portions and make up to volume.
 
Expiry:  30 days
 
Stability:   Chemically stable for 35 days.
 
Storage:  Refrigerate.
 
Shake well before use
 

 
NOTES
  1. A subsequent study2 demonstrated that the bioavailability of itraconazole from this suspension is much lower than that from capsules.
  2. Simple Syrup NF was used in this study.  This is preserved with 0.1% sodium benzoate.  Other suitably preserved syrup could be used instead.
  3. The final product tasted sweet with a musty aftertaste.
  4. Alternatively, the pellets can be formed into a slurry by allowing them to stand in a solution of citric acid for about half an hour.  This should not affect short term drug stability as the pellets are not enteric coated and an acidic medium is normally preferred for absorption.  The preparation of an itraconazole suspension using 1.5% citric acid solution has been described in the literature.3  Doses prepared in this way should be administered immediately.
    As with the extemporaneously prepared suspension the bioavailability of itraconazole may be much lower than that with capsules.3

REFERENCES
  1. Jacobson PA, Johnson CE, Walters JR.  Stability of itraconazole in an extemporaneously compounded oral liquid.  Am J Health-Syst Pharm 1995; 52: 189-91.
  2. Kintzel PE, Rollins CJ, Yee WJ et al.  Low itraconazole serum concentrations following administration of itraconazole suspension to critically ill allogenic bone marrow transplant recipients.Ann Pharmacother 1995; 29: 140-43.
  3. Christensen KJ, Gubbins PO, Gurley BJ, Bowman JL, Buice RG.  Relative bioavailability of itraconazole from an extemporaneously prepared suspension and from marketed capsules.Am J Health-Syst Pharm 1998; 55: 261-5.

 
Formulation in Pharmacy Practice
2nd Edition