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AAPS PharmSciTech

, Volume 19, Issue 5, pp 2118–2132 | Cite as

Fabrication of Nanosuspension Directly Loaded Fast-Dissolving Films for Enhanced Oral Bioavailability of Olmesartan Medoxomil: In Vitro Characterization and Pharmacokinetic Evaluation in Healthy Human Volunteers

  • Jihad Mahmoud Alsofany
  • Manal Yassin Hamza
  • Aly Ahmed Abdelbary
Research Article
  • 140 Downloads

Abstract

Olmesartan medoxomil (OM) is an antihypertensive drug with poor water solubility and low oral bioavailability (28.6%). Accordingly, this study aimed to formulate and evaluate OM nanosuspension incorporated into oral fast-dissolving films (FDFs) for bioavailability enhancement. OM nanosuspension was prepared by antisolvent-precipitation-ultrasonication method and characterized regarding particle size (122.67 ± 5.03 nm), span value (1.40 ± 0.51), and zeta potential (− 46.56 ± 1.20 mV). Transmission electron microscopy (TEM) of the nanosuspension showed spherical non-aggregating nanoparticles. The nanosuspension was then directly loaded into FDFs by solvent casting technique. A full factorial design (22 × 31) was implemented for optimization of the FDFs using Design-Expert® software. Physical and mechanical characteristics in addition to dissolution profiles of the FDFs were investigated. The optimum formula (FDF1) showed 0.43 ± 0.02 kg/mm2 tensile strength, 20.50 ± 2.12 s disintegration time, and 87.53 ± 2.50 and 95.99 ± 0.25% OM dissolved after 6 and 10 min, respectively. Accelerated and long-term shelf stability studies confirmed the stability of FDF1. More than 75% OM was dissolved within 10 min from FDF1 compared with 9.80 and 47.80% for films prepared using coarse drug powder and market tablet, respectively. Relative bioavailability of FDF1 compared to market tablet was assessed in healthy human volunteers. The Cmax value increased significantly from 66.62 ± 14.95 to 179.28 ± 23.96 ng/mL for market tablet and FDF1, respectively. Similarly, the AUC0–72 value significantly increased from 498.36 ± 217.46 to 1083.67 ± 246.32 ng h/mL for market tablet and FDF1, respectively. Relative bioavailability of FDF1 was 209.28%. The highlighted results verified the effectiveness of OM nanosuspension-loaded FDFs in improving OM bioavailability.

KEY WORDS

bioavailability nanosuspension fast-dissolving films factorial design olmesartan medoxomil 

Notes

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

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Copyright information

© American Association of Pharmaceutical Scientists 2018

Authors and Affiliations

  • Jihad Mahmoud Alsofany
    • 1
  • Manal Yassin Hamza
    • 1
  • Aly Ahmed Abdelbary
    • 2
    • 3
  1. 1.Physical Properties Laboratory, Department of PharmaceuticsNational Organization for Drug Control and Research (NODCAR)GizaEgypt
  2. 2.Department of Pharmaceutics and Industrial Pharmacy, Faculty of PharmacyCairo UniversityCairoEgypt
  3. 3.Department of Pharmaceutics and Industrial Pharmacy, Faculty of PharmacyOctober 6 UniversityGizaEgypt

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