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

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 Cmax 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 t1/2and 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.

Development of Biocompatible Nanoparticles of Tizanidine Hydrochloride in Orodispersible Films: In vitro Characterization, Ex vivo Permeation, and Cytotoxic Study on Carcinoma Cells.

BACKGROUND: The main limitations of the therapeutic effectiveness of tizanidine hydrochloride (TNZ) are its low bioavailability due to its tendency to undergo first-pass metabolism and short biological half-life. These factors make it an ideal candidate for formulating orally disintegrating films. OBJECTIVE: The present study was aimed to prepare nanoparticles of tizanidine hydrochloride using biodegradable polymers and loading them on orodispersible films to obtain a sustained release dissolution profile with improved permeability and further study the cytotoxicity on A549 lung carcinoma cells, MCF7 breast cancer cells, and HOP 92 non-small lung adenocarcinoma cells. METHODS: The fast-dissolving film of TNZ HCl was prepared by the solvent-casting method and characterized using scanning electron microscopy, FTIR, and XRD, and evaluated for critical quality attributes for this type of dosage form such as disintegration time, tensile strength, drug content, dissolution, and ex vivo permeability. In vitro cytotoxicity studies were also conducted on cancer cell lines to confirm the cytotoxic effect. RESULTS: The polymeric matrix containing the drug provided a rapid disintegration time varying between 7±2 and 30±2 seconds, adequate tensile strength between 1.4 and 11.25 N/mm2, and improved permeability through porcine buccal mucosa when compared to the reference product. CONCLUSION: A study of the cytotoxic effect on the MCF-7 breast cancer cells and A549 lung carcinoma cells revealed that tizanidine hydrochloride nanoparticles at 2.3 mg/film exhibited an IC50 value of 65.1 % cytotoxicity on MCF-7, approximately 100% on HOP92, and 83.5 % on A549 lung carcinoma cells, thus paving the way for a new paradigm of research for a cytotoxic study on MCF-7, HOP92, and A549 cell lines using the subject drug model prepared as oral films or biodegradable nanoparticles in oral films for site-specific targeting.