Formulation in Pharmacy Practice   2nd Edition

Chlorothiazide is very slightly soluble in water, slightly soluble in alcohol, and soluble in dilute solutions of alkali hydroxide.  Chlorothiazide is a weak acid with pKa values of 6.8 and 9.4.   At low pH (0 - 3.5) the rate of degradation is extremely slow.  Basic solutions of chlorothiazide are much less stable1 as they undergo hydrolysis on standing or heating.  Therefore, it is more appropriate to formulate an acidic suspension than a basic solution for stability reasons.
The USP lists a chlorothiazide suspension and suggests a pH of 3.5 - 4.0 for maximum stability.
In some countries a suspension is commercially available (Diuril® MSD) which contains ethanol, benzoic acid and parabens and has a pH of 3.2 - 4.0.
No published stability studies on suspensions made from tablets have been located.  Various formulations have been developed by individual hospitals.  With some formulations there are considerable problems with caking and dose uniformity.2  At Dunedin Hospital we have developed the following formula.


Chlorothiazide 50mg per mL suspension
Chlorothiazide tablets 500mg 10   
*Sodium carboxymethylcellulose g
Parabens 0.1  %
Glycerol 10  mL
Citric acid monohydrate 500  mg
Water to   100  mL
*Alternatively, use a base of methylcellulose 1%.
Expiry:  30 days
Storage:  Refrigeration.  Protect from light.
SHAKE THE BOTTLE:  This is extremely important and the significance should be explained to caregivers.

  1. Preservative free formulation:
    Omit the parabens.  An expiry date of 7 days suggested.

  1. Longer M.A. In: Conners K.A., Amidon G.L., Stella V.J.  Chemical Stability of Pharmaceuticals.
    New York: John Wiley, 1986: 345-50.
  2. Tucker I.G., Geddes J.A., Stewart P.J.  Dose variations from an extemporaneously prepared chlorothiazide suspension.  Aust J Hosp Pharm 1982; 12: 59-63.

Formulation in Pharmacy Practice
2nd Edition