Author : S. Alghurabi, Hamid
Solubility enhancement of ibuprofen in oral liquid preparations using basic amino acids as counter ions
karbala journal of pharmaceutical sciences,
Volume 8, Issue 13, Pages 337-347
Background: The recent advance in combinatorial chemistry to find new drug candidates has increased the number of compounds having low solubility profile, which makes them more difficult and less desirable for further dosage form development. Salt formation is one of the most common and preferred method for increasing the aqueous solubility of poor soluble drugs. Basic amino acids are considered fairly strong bases with the advantages of self-buffering in the formulation as well as producing salts that have pleasant tastes and less likely to be affected by the common-ion effect.
Objective: The main aim of the project will focus on the development of a universal solubilising vehicle for the formulation of insoluble acidic drug candidates as liquid preparations through salt formation by using acidic amino acids as counter ions.
Materials and Methods: Ibuprofen was chosen as a drug candidate and reacted with two different basic amino acids (lysine and arginine). Phase solubility diagram was obtained by measuring the solubility of ibuprofen free acid with different concentrations of basic amino acid (lysine and arginine) by UV spectrophotometer. The amino acid solutions pH was measured using pH meter. The stability of the prepared salts in in the presence of other solvents such as ethanol and glycerin and other salts such as potassium chloride was monitored by measuring the solubility of the drug over time.
Results: Increasing the concentrations of both arginine and lysine resulted in increasing pH of the solution and consecutively improving the solubility of ibuprofen by 1371 and 242 fold, respectively. The prepared salts showed high stablity in the presence of ethanol, glycerin and potassium chloride over a period of 6 months.
Conclusion: salt formation is very effective method in solubility enhancement provided that the appropriate counter-ion with the correct concentration and pH condition is used.