AAPS PharmSciTech

, Volume 19, Issue 5, pp 2087–2102 | Cite as

Multi-Layer Self-Nanoemulsifying Pellets: an Innovative Drug Delivery System for the Poorly Water-Soluble Drug Cinnarizine

  • Ahmad Abdul-Wahhab ShahbaEmail author
  • Abid Riaz Ahmed
  • Fars Kaed Alanazi
  • Kazi Mohsin
  • Sayed Ibrahim Abdel-Rahman
Research Article


Beside their solubility limitations, some poorly water-soluble drugs undergo extensive degradation in aqueous and/or lipid-based formulations. Multi-layer self-nanoemulsifying pellets (ML-SNEP) introduce an innovative delivery system based on isolating the drug from the self-nanoemulsifying layer to enhance drug aqueous solubility and minimize degradation. In the current study, various batches of cinnarizine (CN) ML-SNEP were prepared using fluid bed coating and involved a drug-free self-nanoemulsifying layer, protective layer, drug layer, moisture-sealing layer, and/or an anti-adherent layer. Each layer was optimized based on coating outcomes such as coating recovery and mono-pellets%. The optimized ML-SNEP were characterized using scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD), in vitro dissolution, and stability studies. The optimized ML-SNEP were free-flowing, well separated with high coating recovery. SEM showed multiple well-defined coating layers. The acidic polyvinylpyrrolidone:CN (4:1) solution presented excellent drug-layering outcomes. DSC and XRD confirmed CN transformation into amorphous state within the drug layer. The isolation between CN and self-nanoemulsifying layer did not adversely affect drug dissolution. CN was able to spontaneously migrate into the micelles arising from the drug-free self-nanoemulsifying layer. ML-SNEP showed superior dissolution compared to Stugeron® tablets at pH 1.2 and 6.8. Particularly, on shifting to pH 6.8, ML-SNEP maintained > 84% CN in solution while Stugeron® tablets showed significant CN precipitation leaving only 7% CN in solution. Furthermore, ML-SNEP (comprising Kollicoat® Smartseal 30D) showed robust stability and maintained > 97% intact CN within the accelerated storage conditions. Accordingly, ML-SNEP offer a novel delivery system that combines both enhanced solubilization and stabilization of unstable poorly soluble drugs.


self-nanoemulsifying drug delivery systems (SNEDDS) self-nanoemulsifying pellets poorly water-soluble drugs fluid bed coating solidification 



This work was funded by National Plan for Science, Technology, and Innovation (MAARIFAH), King Abdulaziz City for Science and Technology, Kingdom of Saudi Arabia, Award Number (11NAN1953-02). The authors acknowledge “Kayyali Chair for Pharmaceutical Industries” for hosting the work.


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Copyright information

© American Association of Pharmaceutical Scientists 2018

Authors and Affiliations

  • Ahmad Abdul-Wahhab Shahba
    • 1
    Email author
  • Abid Riaz Ahmed
    • 2
  • Fars Kaed Alanazi
    • 1
  • Kazi Mohsin
    • 1
  • Sayed Ibrahim Abdel-Rahman
    • 3
  1. 1.Kayyali Chair for Pharmaceutical Industries, Department of Pharmaceutics, College of PharmacyKing Saud UniversityRiyadhKingdom of Saudi Arabia
  2. 2.Merck KGaADarmstadtGermany
  3. 3.Department of Industrial Pharmacy, Faculty of PharmacyAssiut UniversityAssiutEgypt

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