Mixed Pluronic/lecithin micelles formulation for oral bioavailability of candesartan cilexetil drug: in vitro characterization and in vivo pharmacokinetic investigations

Abstract

Objective

This study aimed to develop a mixed polymeric micelle formulation incorporating candesartan cilexetil (CAND) drug to enhance its oral bioavailability for the better treatment of hypertension.

Methods

A Box–Behnken design was utilized to optimize the CAND-incorporated mixed polymeric micelles formulation (CAND-PFLC) consisting of Pluronics (P123 and F68) and lecithin (LC). The optimized CAND-PFLC micelles formulation was characterized for size, shape, zeta potential, polydispersity index (PDI), and entrapment efficiency (%EE). An in vitro release study, ex vivo permeability investigation, and an in vivo pharmacokinetic analysis were carried out to evaluate the performance of the formulation.

Results

The optimized CAND-PFLC micelles formulation demonstrated a spherical shape, a particle size of 44 ± 2.03 nm, a zeta potential of −7.07 ± 1.39 mV, a PDI of 0.326 ± 0.06, and an entrapment efficiency of 87 ± 3.12%. The formulation exhibited excellent compatibility, better stability, and a noncrystalline nature. An in vitro release study revealed a faster drug release of 7.98% at gastric pH in 2 hrs and 94.45% at intestinal pH within 24 hrs. The ex vivo investigation demonstrated a significantly enhanced permeability of CAND, with 94.86% in the micelle formulation compared to 9.03% of the pure drug. In vivo pharmacokinetic analysis showed a 4.11-fold increase in oral bioavailability of CAND compared to the marketed formulation.

Conclusion

The CAND-PFLC mixed micelle formulation demonstrated improved performance compared to pure CAND, indicating its potential as a promising oral drug delivery system for the effective treatment of hypertension.

Graphical Abstract

Keywords:

• Candesartan cilexetil drug
• mixed polymeric micelles
• Box–Behnken design
• in vitro characterization
• in vivo pharmacokinetics

Acknowledgments

XRD measurements were acquired on the instrument purchased under the DST-FIST Program of the Applied Physics Department (SR/FST/PS-II/2017/20).

Author contributions

Homraj Mahajan: Investigation; Methodology, Data analysis; Writing-original draft.

Hemal Tandel: Conceptualization; Supervision; Project administration; Writing-original draft; Review and editing.

Hemil S Patel: Supported in the experimental work; Software; Artwork.

Rakesh K Sharma: Supervision; Project administration; Writing-original draft; Review and editing.

Debes Ray and Vinod K Aswal: Contributed to the SANS measurements.

All authors read and approved the final manuscript.

Ethics approval

The Animal study protocol was approved by The Institutional Animal Ethics Committee (The Maharaja Sayajirao University of Baroda, Gujarat, India) No.MSU/IAEC/2021-22/2129).

Patient consent statement

Not applicable.

Disclosure statement

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

Data availability statement

The authors confirm that all data underlying the findings are fully available without restriction. All relevant data are within the paper.

Clinical trial registration

Not applicable.

Additional information

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.