Melting point depression for enhanced dissolution rate of eslicarbazepine acetate

BackgroundEslicarbazepine acetate (ESL) is antiepileptic agent which is approved for use as single therapy or in combination with other drugs. However, it suffers from poor oral bioavailability. Modulation of drug crystallinity can be utilized as an approach for enhancing drug dissolution.ObjectiveAccordingly, the aim of this study was to investigate possible eutectic system formation between eslicarbazepine with either tartaric acid or citric acid.MethodologyEslicarbazepine acetate was subjected to wet co-grinding with tartaric acid or citric acid at different molar ratios. The prepared formulations were assessed using Fourier-transform infrared (FTIR), X-ray powder diffraction (XRPD), differential scanning calorimetry in addition to dissolution studies.ResultsThe characterization techniques confirmed eutectic system formation with tartaric and citric acid with the optimum molar ratio for eutexia being 1:1 for both substances. Development of eutectic systems significantly enhanced the dissolution rate of ESL. Increasing the ratio of tartaric acid higher than the optimum ratio for eutexia resulted in additional increase in drug dissolution rate. This suggested the impact of pH modification on drug dissolution rate. The enhanced dissolution rate in case of the formulations containing ESL and citric acid was accredited to combined effect of eutaxia and pH modulation. These explanations were proven from investigating the dissolution rate of the physical mixtures which were inferior in their dissolution rate compared with the prepared formulations.Conclusionco-processing of ESL with either citric acid or tartaric acid resulted in hastened dissolution rate which was accredited to combined effect of eutexia with pH modification.

Automated summary

This study aimed to enhance the dissolution rate of eslicarbazepine acetate (ESL) by forming eutectic systems with tartaric acid or citric acid. The eutectic system formation with both tartaric and citric acid was confirmed, with the optimum molar ratio being 1:1 for both substances. The co-processing of ESL with either citric acid or tartaric acid resulted in significantly enhanced dissolution rate, attributed to the combined effect of eutexia and pH modification.