Empagliflozin containing chitosan-alginate nanoparticles in orodispersible film: preparation, characterization, pharmacokinetic evaluation and its in-vitro anticancer activity

Abstract

Objective

The main objective of this study was to develop the orodispersity film containing chitosan-alginate nanoparticles to improve dissolution profile, therapeutic effect with improved bioavailability of empagliflozin through oral route noninvasively for further cytotoxicity study.

Methods

The nanoparticles were developed through two-step mechanisms ionotropic pre-gelation and polyelectrolyte complexation methods. The prepared nanoparticles were added to a polymer matrix containing hypromellose, polyvinyl alcohol, and maltodextrin and cast to rapidly dissolving thin film by solvent casting method.

Results

The physicochemical characteristics of empagliflozin in the orodispersible film were most favorable for further studies. This formulation has achieved a higher permeability (7.2-fold) as compared to the reference drug product (Jardiance) after 45 min. In vivo pharmacokinetic studies in Wistar rats have revealed that chitosan-alginate empagliflozin nanoparticles in the orodispersible film were 1.18-fold more bioavailable in comparison to free empagliflozin in orodispersible film. The C_max observed for the empagliflozin-loaded orodispersible film was 15.42 ± 5.13 μg/mL in comparison to 18.21 ± 5.53 μg/mL for empagliflozin nanoparticle-containing orodispersible film and 12.19 ± 6.71 μg/mL for freed rug suspension. The t_1/2and AUC_0-t values for chitosan-alginate nanoparticles of empagliflozin in the orodispersible film were found1.4-fold more than empagliflozin loaded orodispersible film (without nanoparticles). The cytotoxicity study has shown that chitosan-alginate nanoparticles of empagliflozin in orodispersible film achieved a 2.5-fold higher cytotoxic effect than free empagliflozin in orodispersible film in A549lung cancer cells.

Conclusions

This study provides evidence that chitosan-alginate nanoparticles of empagliflozin in orodispersible film can be an effective drug carrier system to improve sustained effect with better bioavailability of poorly water-soluble drug.

Keywords:

• Anticancer agent
• lung cancer
• nanomedicine
• oral bioavailability
• orodispersible film
• physicochemical characterization
• stability study

Acknowledgments

The authors thank the Indian Institute of Technology (IIT), Delhi, G.D. Goenka University, Gurugram, Pinnacle Biomedical Research, Bhopal, Sriram Institute of Industrial Research, Delhi, and Onisome Labs, Mohali for providing facilities for research purposes.

Author contributions

All authors were involved in the study design, analysis, and interpretation of data, and contributed to the preparation of this manuscript, including its critical review and approving the final draft and accept full responsibility for its content.

Disclosure statement

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

Additional information

Funding

This research was partially financial supported by the Science and Engineering Research Board (SERB), New Delhi, India [grant number EEQ/2019/000218] to RP.