Formulation in Pharmacy Practice  

ISONIAZID
 
The solubility of isoniazid in water is approximately 1 in 8.  The pH of a 1% aqueous solution is 5.5 - 6.5.  The pH of isoniazid injection is adjusted to 6 - 7.  Isoniazid may crystallise from solution at low temperatures.  If this occurs products should be gently warmed to room temperature to redissolve.  No formal stability studies of isoniazid oral liquids have been located.
Formula A is based on information published in the British Pharmaceutical Codex (BPC 1973) and Martindale (29th Edition).  Formula B is a suggested alternative.

Formula A

Isoniazid Solution 50mg per 5mL
 
Isoniazid powder BP 1000  mg
Citric acid monohydrate 250  mg
#Sodium citrate 1200  mg
Glycerol 20  mL
Parabens 0.1  %
Water to   100  mL
 
The original formula contained chloroform water as a preservative.
Parabens is suggested as an alternative.  Concentrated anise water has also been omitted.
#The inclusion of sodium citrate is preferred to provide a pH buffer system.  However, citric acid alone is probably sufficient for an expiry date not exceeding 30 days.
 
Expiry:  30 days
 
Storage:  Room temperature (less than 25°C) or refrigerate.
If stored in a refrigerator check for crystallisation and warm to room temperature to redissolve if necessary.
Protect from light and store in amber containers.
 
Shake well before use
 
NOTES
  1. Do not use syrups (glucose, fructose, sucrose etc.) in the formulation due to incompatibility with isoniazid.
  2. If isoniazid powder is not available crushed tablets could be used but insoluble excipients will form a suspension.  A suspending agent such as 1% methylcellulose is recommended.
  3. A modified version of Formula A using crushed tablets is as follows:
    Isoniazid tablets qs; Citric acid monohydrate 250mg; Glycerol 20mL; Parabens 0.1%; Methylcellulose 1%, 50mL; Water to 100mL.
    It is essential to shake this preparation before use as drug may be bound to excipients or may have precipitated from solution.
 

 
Formula B1

Isoniazid Suspension 100mg per 5mL
 
Isoniazid tablets 100mg 30   
HPMC 1% mucilage 75  mL
Water 20  mL
Sorbitol solution 70 % to   150  mL
 
Expiry:  30 days
 
Storage:  Refrigerate.   Protect from light.   Use amber containers.
 
Shake well before use
 
NOTE
  1. Nahata and Hipple2 have described the following formulation also using sorbitol:
    Isoniazid tablets (10 x 100mg) crushed and mixed with 10mL of water and made up to 100ml with sorbitol 70%.  A stability period of 21 days under refrigeration was stated although no formal testing was carried out.
 

 
REFERENCES
  1. Personal Communication:  Ron Chambers, PMH, Perth, Western Australia.
  2. Nahata MC, Hipple TF.  Pediatric Drug Formulations. Cincinnati, Ohio: Harvey Whitney Books
    Company; 1992.

 
Formulation in Pharmacy Practice
2nd Edition