Object:

To prepare and submit an aqueous injection of a poorly water-soluble drug using hydrotropic solubilization technique.

Principle:

The term hydrotropy has been used to designate the increase in solubility in water of various substances due to the presence of large amount of additives. The mechanism by which the effect occurs is not clear. Some workers have speculated that hydrotropy is another type of solubilization, with the solute dissolved in oriented clusters of the hydrotropic agent.

The influence of large concentrations of sodium benzoate on the solubility of caffeine is a classic example of this phenomenon applied to a pharmaceutical system (Caffeine injection made with the help of sodium benzoate is official in I.P. and U.S.P.) Other examples of hydrotropic solubilization include the solubilization of benzoic acid with sodium benzoate, and of theophylline with sodium acetate and glycinate.

Examples of some hydrotropic agents are – sodium benzoate, sodium citrate, sodium ascorbate, sodium salicylate, sodium gentisate, urea, niacinamide. A concentrated aqueous solution of sodium benzoate enhances the aqueous solubility of several poorly soluble drugs like ibuprofen, ketoprofen , flurbiprofen, indomethacin, norfloxacin, gatifloxacin, ornidazole, aspirin, salicylic acid, hydrochlorthiazide, frusemide, piroxicam, paracetamol, tinidazole and metronidazole. Similarly, concentrated aqueous solution of urea enhances the aqueous solubility of several poorly water-soluble drugs like atenolol, diclofenac sodium, paracetamol, aspirin, metronidazole, norfloxacin, salicylic acid, hydrochlorothiazide and tinidazole.

Formula for injection of salicylic acid:

  1. Salicylic acid500 mg
  2. Sodium citrate(dehydrate)2.5 g
  3. Water for injection q.s.10 ml

Procedure:

Take 2.5 g of sodium citrate (dihydrate) in a 10 ml volumetric flask and add 6 ml water for injection (see note no 1) and shake flask to dissolve sodium citrate (slight heating may be employed to hasten dissolution process). When clear solution results, add 500 mg of salicylic acid and shake the flask to get a clear solution of salicylic acid. Then make up the volume to 10 ml with water for injection (see the note no 2). Filter the solution to remove any foreign particles and fill 2-2 ml solution in four vials of 5 ml capacity (discard the remaining solution). Apply the rubber closures and aluminum seals on the mouth of vials. Sterilize the vials in autoclave for 30 minutes at 10 pounds per square inch pressure (pressure cookers can be employed for sterilization).

Each vial contains 100 mg of salicylic acid (as model drug) solubilized with the help of 500 mg of sodium citrate (as model hydrotropic agent). In the absence of sodium citrate, even 10 mg of salicylic acid cannot give clear solution in 2 ml of water.

Note:1 - -In the absence of water for injection, ordinary distilled water can be used for practical purpose.

2 - - If 10 ml volumetric flask is not available, use 50 ml or 100 ml bottle to dissolve sod citrate, salicylic acid etc and make up thevolume to 10 ml in measuring cylinder.

References

  1. Lachman Leon, Lieberman HA,Kanig JL, “ The Theory and Practice of Industrial Pharmacy’’, 3nd edition (Indian edition), Varghese publication house, 1987, 466.
  1. Maheshwari R K, Chavada V, Varghese S, Shahoo K, Analysis of Bulk Sample of Salicylic Acid by Application of Hydrotropic Solubilization Method, Indian Journal of Pharmaceutical Sciences, 2008, volume 70: pages 823–825.

1