Empagliflozin containing chitosan-alginate nanoparticles in orodispersible film: preparation, characterization, pharmacokinetic evaluation and its in-vitro anticancer activity. (3rd July 2022)

• Record Type: Journal Article
• Authors: Sinha, Suhani; Sonali, ; Garg, Vandana; Thapa, Sonia; Singh, Shashank; Chauhan, Mahima; Dutt, Rohit; Singh, Rahul Pratap
• Is Part Of: Drug development and industrial pharmacy. Volume 48:Number 7(2022)
• Page Start: 279
• Page End: 291
• Publication Date: 2022-07-03
• Subjects: Anticancer agent -- lung cancer -- nanomedicine -- oral bioavailability -- orodispersible film -- physicochemical characterization -- stability study; Pharmaceutical chemistry -- Periodicals; Pharmaceutical industry -- Periodicals; Drug Industry -- Periodicals; Technology, Pharmaceutical -- Periodicals; 615.05
• DOI: 10.1080/03639045.2022.2108829
• Languages: English
• ISSNs: 0363-9045

Abstract

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 t1/2 and AUC0-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.