Diclofenac Solubility:  Independent Determination of the Intrinsic Solubility of Three Crystal Forms

Abstract

The solubility in water of diclofenac ({2-[(2,6-dichlorophenyl)amino]phenyl}acetic acid), a potent nonsteroidal anti-inflammatory drug, has been investigated. The various solid forms have been characterized by thermogravimetric analysis, differential scanning calorimetry, and X-ray diffraction. The commercially available form of diclofenac is the anhydrous sodium salt. This was recrystallized from ethanol and precipitated as a hydrate containing four diclofenac anions, four sodium cations, and nineteen water molecules per unit cell. This crystal structure is similar to but different from an earlier report of the structure. Crystals of the acid form of diclofenac were anhydrous and corresponded to an earlier crystal structure. Separate solubility measurements on all three of these solid forms of diclofenac gave consistent results for the intrinsic solubility. The aqueous solubility values reported in the literature for diclofenac are spread over a large range, with a factor of 100 separating the largest and the smallest. Our value is at the smaller end of this range. It is the only one supported by three independent procedures and rigorous characterization of the solid forms. The experimental conditions were precisely controlled.

Equilibrium solubility measurement of ionizable drugs – consensus recommendations for improving data quality

“…This technique allows one to have a precise control of the rate of transformation of one form into the other, depending on the conditions of the experiment used. This approach has been applied to numerous compounds (bases, acids and zwitterions), generally obtaining the more stable polymorph; in many cases they proved to be newly-identified polymorphs [1,66,[71][72][73][74].…”

Biodegradable system for drug delivery of hydrolytically labile azanucleoside drugs

“…Release of DIC from the beads was also confirmed by the test (data not shown), but experiment was complicated by the limited solubility of DIC in the concentrations suitable for "100% release" of azanucleosides 15 .…”

“…Since, microbeads may cause local irritation resulting in inflammation, nonsteroidal anti-inflammatory drug, diclofenac (DIC) was added to the polymeric matrix 15 . DIC is hydrophobic and is soluble in polymeric matrix.…”

Comparative Permeation Studies between Scale Region of Shed Snake Skin and Human Skin In vitro

“…Quantification of the compounds was carried out by integration of peak area compared with the relevant standards. Using paired t-test to compare with UV-spectrophotometry of the same samples, analysis of diclofenac sodium was the only compound which was found significant different which might be explained by the findings of Llinàs et al [17] . Therefore, the analysis of permeated diclofenac sodium in our study was performed by HPLC.…”