Investigation of the Solubility Enhancement of Aceclofenac by Mixed Hydrotropes at Minimal Safe Concentrations

摘要

Background: Aceclofenac is categorized as a Class II drug under the Biopharmaceutics Classification System, which inherently exhibits low solubility and bioavailability. The drug's poor aqueous solubility significantly impedes its absorption. Hence, significant research efforts are directed toward various strategies to improve its aqueous solubility and dissolution. Various sophisticated formulation strategies have been developed to overcome this limitation. Among them is the hydrotropic solubilization technique, which offers a simple, promising and more biocompatible alternative that does not require chemical modification of hydrophobic drugs.

Objectives: This study aimed to investigate the solubility-enhancing effect of individual hydrotropes on aceclofenac and to evaluate the solubility-enhancing effect of a mixed hydrotropic system.

Methodology: Solutions of the drug were prepared in methanol to obtain the calibration curve, and the absorbance was read at λ ≈ 273.2. Hydrotropes (urea, sodium benzoate, and sodium citrate) of analytical grade were prepared at concentrations of 1, 2, 4, 6 and 10% w/v, respectively. The solubility enhancement of aceclofenac was determined using UV – Visible spectrophotometry. Blends containing the three hydrotropes were also analysed. Thin Layer Chromatography (TLC) and Fourier Transform Infrared (FTIR) spectroscopy were used to investigate possible complexation of the drugs and hydrotropes.

Results: The 10 %w/v sodium citrate hydrotrope gave the highest solubilizing effect (solubility enhancement ratio of 365.80). At 1 %w/v concentration of the mixed hydrotropes (urea, sodium benzoate, sodium citrate), the solubility enhancement ratio was found to be 102.49. The TLC and FT-IR studies showed no interactions between functional groups in the drugs and hydrotropes.

Conclusion: The three hydrotropes investigated enhanced the aqueous solubility of aceclofenac. Mixed hydrotropes (urea, sodium citrate and sodium benzoate) at 1 % w/v gave the highest solubility enhancement ratio; thus suggesting that mixed hydrotropes are a preferred vehicle for the aqueous solubility enhancement of aceclofenac.