Formulation in Pharmacy Practice   2nd Edition

DIAZEPAM
 
 
Diazepam has a solubility in water of 0.05mg per mL; 41mg per mL in 95% ethanol and 17mg per mL in propylene glycol.  In aqueous solution diazepam is relatively stable at pH 4 - 8 with maximum stability at about pH 5.1,2  Stability and solubility is increased in mixed solvent systems of water, ethanol and propylene glycol.

Newton et al3 reported that a diazepam oral liquid prepared from tablets in a syrup base with 30% propylene glycol and 5% ethanol was stable for at least 14 days at room temperature in amber glass bottles.  The amount of propylene glycol in this formulation may be unacceptable.  In the same study, a 1mg per mL suspension compounded from tablets and unpreserved Syrup USP, was reported to be chemically stable, but dose uniformity may be erratic as the preparation is a solution/suspension of diazepam.

Strom4 studied the stability of a diazepam oral liquid prepared from tablets containing 3.6% v/v of ethanol 95% and 5% v/v of propylene glycol in a syrup base with 1% sodium carboxymethylcellulose and 2% magnesium aluminium silicate.  The pH was adjusted to 4.2 with hydrochloric acid.  The preparation was stable for 60 days at room temperature or under refrigeration.

Most tablet brands disperse rapidly and this option should be considered before making an oral liquid.

The following formulation is based on published studies and stability data.

Formula

Diazepam Oral Liquid
 
Diazepam tablets qs   
Ethanol 95% mL
Methylcellulose g
Parabens 0.1  %
Glycerol 20  mL
Water to   100  mL
 
Expiry:  30 days.
 
Storage:  Refrigerate
 
Shake well before use
 

 
NOTE
  1. Most of the diazepam may be in solution but this has not been validated.  A suspending agent has been included in case some of the drug is in suspension.

REFERENCES
  1. Dobrinska MR In: Connors KA, Amidon GL, Stella VJ.  Chemical stability of Pharmaceuticals.  New York: John Wiley, 1986: 412-20.
  2. Trissel LA.  Stability of Compounded Formulations.  Washington DC: American Pharmaceutical Association, 1996.
  3. Newton DW, Schulman SG, Becker CH.  Limitations of compounding diazepam suspensions from tablets.
    Am J Hosp Pharm 1976; 33: 450-2.
  4. Strom JG, Agbai KU.  Formulation and stability of diazepam suspension compounded from tablets.
    Am J Hosp Pharm 1986; 43: 1489-91.
 
 
     

 
Formulation in Pharmacy Practice
2nd Edition
© 2001 PharmInfoTech
ISBN 0-473-07577-6