AAPS PharmSciTech

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Preparation and Characterization of an Oral Norethindrone Sustained Release/Controlled Release Nanoparticles Formulation Based on Chitosan

  • Bashar M. Altaani
  • Suhair S. Al-NimryEmail author
  • Razan H. Haddad
  • Rana Abu-Dahab
Research Article


Norethindrone has short half-life and low bioavailability. The objective was to prepare an oral Sustained Release/Controlled Release (SR/CR) Liquid Medicated Formulation (LMF) to enhance bioavailability and improve patient compliance. Norethindrone was solubilized in HP-β-CD then complexed with different concentrations of Low Molecular Weight Chitosan (LMWC) (mucoadhesive). PolyElectrolyte Complexes (PECs) were homogenized with oleic acid using different concentrations of tween 80 to form LMFs (nanoemulsions). PECs and LMFs were characterized using different techniques. LMF 2 (optimum formula containing 2.5% w/v LMWC 11 kDa) was administered orally to dogs and mice for pharmacokinetic and adhesion evaluation. DSC, FTIR spectroscopy and SEM images indicated complex formation. Mean diameters of PECs were 183–425 nm, mean zeta potentials were + 18.6–+ 31 mV, and complexation efficiencies were 18.0–20.6%. Ten to fifteen percent tween was needed to prepare homogenous LMFs. Mean diameter of LMF 2 was 10.5 ± 0.57 nm, mean zeta potential was − 11.07 ± − 0.49 mV, encapsulation efficiency was 95.28 ± 1.75%, and each mL contained 145.5 μg norethindrone. SEM images showed spherical homogeneous oil droplets. All of these parameters were affected by molecular weight and concentration of chitosan. Norethindrone release from LMFs was controlled (zero order) for 96 h. It was little affected by molecular weight and concentration of chitosan but affected by concentration of tween 80. LMF 2 adhered to GIT for 48 h and enhanced the bioavailability. It showed no cytotoxicity after considering dilution in GIT and was stable for 3 months refrigerated. In conclusion an effective SR/CR LMF was prepared.


low molecular weight chitosan hydroxyPropyl-beta-cyclodexrin norethindrone sustained/controlled release nanoemulsion 


Funding Information

The authors received financial support (347/2015) from Jordan University of Science and Technology.

Supplementary material

12249_2018_1261_MOESM1_ESM.docx (20 kb)
ESM 1 (DOCX 19 kb)


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Copyright information

© American Association of Pharmaceutical Scientists 2019

Authors and Affiliations

  • Bashar M. Altaani
    • 1
  • Suhair S. Al-Nimry
    • 1
    Email author
  • Razan H. Haddad
    • 1
  • Rana Abu-Dahab
    • 2
  1. 1.Department of Pharmaceutical TechnologyJordan University of Science and TechnologyIrbidJordan
  2. 2.Department of Biopharmacy and Clinical PharmacyThe University of JordanAmmanJordan

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