Formulation in Pharmacy Practice -eMixt

Azathioprine
 
 This information is provided by Pharminfotech           Please read disclaimer before using this information          Back to Formulation Index Page

A New Zealand standardised formulation is available Formula and Batch Sheet
This formula uses Ora-Blend/SF or Ora-Plus and Ora-Sweet/SF; 1:1, and has been approved by the Extemporaneous Compounding Pharmacists' Group.
Alternatives are given below.


Azathioprine is a weak base with a pKa of 8.2.  Azathioprine is practically insoluble in water, but dissolves in dilute solutions of alkali hydroxides.  The USP injection is azathioprine sodium and has a pH of 9.8 - 11.0.

Azathioprine is stable in acidic or neutral conditions but is hydrolysed to mercaptopurine at alkaline pH.1  Therefore it is more appropriate to make a suspension with a neutral pH than a solution at an alkaline pH.

A suspension prepared from azathioprine tablets and a base consisting of one third methylcellulose solution 9% (Cologel) and two thirds of cherry flavored syrup, is reportedly chemically stable for at least 14 days at room temperature and under refrigeration.2

Azathioprine 50mg per mL prepared from tablets in a vehicle of Ora-Sweet and Ora-plus 1:1 or Ora-Sweet SF and Ora-Plus 1:1 or cherry syrup is chemically stable for 60 days at 5 or 25°C protected from light.3  The final pH of these preparations was in the range 3.5 - 4.3.  Microbial testing was not performed.

Whenever possible azathioprine suspension should be made in accordance with the directions of the published studies2,3 but if commercial suspending vehicles are not available the following is suggested based on evaluation of the literature:


Formula
(
only if ingredients above are not available)

Azathioprine Suspension 50mg per mL
Azathioprine tablets qs 
*Methylcellulose 1% 50  mL
Syrup 20  mL
Parabens 0.1  %
Water to   100  mL
*Use either 50mL of a 1% solution or 0.5g per 100mL.  If the final product is too viscous reduce the amount of methylcellulose.  Sodium carboxymethylcellulose is probably best avoided as it may give rise to a neutral or alkaline pH.
If possible check the pH and if necessary add a small amount of citric acid (50 - 100mg) to give a final pH in the range 4 - 5.
Expiry:  30 days suggested.
Storage:  Refrigerate.  Protect from light.
Shake well before use
 

 
REFERENCES
  1. Van Scoik K.  Azathioprine.  In: Conners K.A., Amidon G.L., Stella V.J.  Chemical Stability of Pharmaceuticals.  New York: John Wiley 1986.
  2. Dressman JB, Poust RI.  Stability of allopurinol and five antineoplastics in suspension.  Am J Hosp Pharm 1983; 40: 616-8.
  3. Allen LV, Erickson MA.  Stability of acetazolamide, allopurinol, azathioprine, clonazepam, and flucytosine in extemporaneously compounded oral liquids.  Am J Health-Syst Pharm 1996; 53: 1944-9.
 
 
     

Formulation in Pharmacy Practice
Page updated September 2011