Utilization of Co-evaporation Technique for Enhancement the Solubility and Dissolution Rate of Etodolac

Abstract

Etodolac (ETD), a member of non-steroidal anti-inflammatory drugs (NSAIDs), has a poor aqueous solubility. Long term administration of ETD causes severe gastrointestinal disturbances such as peptic ulcer and bleeding. The enhancement of its solubility and dissolution profile is expected to improve its bioavailability and reduce its side effects. In the present study, we tried to enhance the aqueous solubility and dissolution rate of ETD by two co-evaporation techniques. The first one is the formation of solid dispersion with different hydrophilic carriers, including polyethelene glycol (PEG 4000), polyvinyl pyrrolidones (PVP K25 and PVP K90) and urea. The second method is the formation of solid adsorbates using inert carriers such as avecil PH 101, bentonite and aerosil 200 as adsorbents. Co-evaporates were prepared at (1:1 w/w), (1:3 w/w) and (1:5 w/w) ETD to carrier ratios and the corresponding physical mixtures were also prepared. The solubility and dissolution studies of all formulations were measured. Moreover, the physicochemical properties of the modified co-evaporates were characterized using different techniques including, differential scanning calorimetry (DSC), infrared spectroscopy and X-ray diffractometry (XRD) analysis. The results showed that the co-evaporates exhibited higher dissolution rate than the corresponding physical mixtures and both showed higher dissolution rate than the unmodified drug. Increase polymer concentration led to increase in the dissolution rate of drug. Plus, the dissolution rate was enhanced by increasing the temperature of the dissolution medium. Avecil PH 101 exhibited the highest dissolution rate over all other polymers. Infrared studies showed no interaction between the drug and the investigated carrier. The DSC and XRD studies indicated the conversion of ETD to an amorphous state. The enhancement of the drug solubility may be attributed to the increase of drug surface area, the wettability, formation of hydrogen bonds and the conversion to amorphous state.