Evaluating solubility of sodium diclofenac in binary and ternary solvent systems to obtain a suitable solvent system for preparation of injectable dosage form

Benzyl alcohol is frequently used as a co- solvent in formulation of sodium diclofenac injectable solution. Benzaldehyde is the main toxic oxidation product occurring as a result of oxidation on long-term storage or heat sterilization of parenteral dosage forms containing benzyl alcohol, which is responsible for paraplegia. The aim of this study was the determination of Na- diclofenac solubility in various solvent systems to obtain a suitable mixture for formulation of Nadiclofenac injection form without using benzyl alcohol as a co-solvent.

For this mean the solubility of drug wasdetermined in various commonly used solvents, binary and ternary mixtures. Triangle diagram was used for evaluation of solubility in ternary mixtures. The best systems in view point of having higher solubilityvalues were selected and injection forms were prepared by adding an antioxidant and preservative. Obtained formulations were kept in different temperatures for days and evaluated for physical stability after this period. Finally the best formulation was chosen for determining of shelf- life.

The results showed that Na- diclofenac had the highest solubility in some binary(water ethyl alcohol and water-PEG300) and ternary(water, ethyl alcohol and PEG300) systems. These systems were selected for stability tests. The most of them were stable in these conditions. Among the evaluated formulations, the best system having saturated solubility 344.4 mg/ml and containing 10, 35 and 55% (v/v) of ethyl alcohol, PEG300 and water respectively, evaluated for shelf- life test. The result indicated that this selected formulation had a shelf- life about 2.5 years.

prepared formulation could be able to use as a stable and safe injectable dosage from.