Melting point depression for enhanced dissolution rate of eslicarbazepine acetate

Abstract

Background

Eslicarbazepine 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.

Objective

Accordingly, the aim of this study was to investigate possible eutectic system formation between eslicarbazepine with either tartaric acid or citric acid.

Methodology

Eslicarbazepine 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.

Results

The 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.

Conclusion

co-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.

Keywords:

• Eslicarbazepine acetate
• tartaric acid
• citric acid
• eutexia dissolution efficiency

Author contributions

Ebtehal M. Dorgham: Investigation, Data curation, Visualization and writing original draft. Mona F. Arafa: Methodology, Data Curation, Visualization, Writing, Reviewing and Editing. Gamal M. El Maghraby: Conceptualization, Methodology, Visualization, Supervision, Writing, Reviewing and Editing. Ebtessam A. Essa: Methodology, Data Curation, Supervision, Visualization, Writing, Reviewing and Editing.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data are available upon request

Additional information

Funding

Self-funded