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Novel Self-Nanoemulsifying Drug Delivery Systems (SNEDDS) for Oral Delivery of Cinnarizine: Design, Optimization, and In-Vitro Assessment

AAPS PharmSciTech volume 13, pages 967–977 (2012)Cite this article

Abstract

Due to its extreme lipophilicity, the oral delivery of cinnarizine (CN) encounters several problems such as poor aqueous solubility and pH-dependent dissolution, which result in low and erratic bioavailability. The current study aims to design self-nanoemulsifying drug delivery systems (SNEDDS) of CN that circumvent such obstacles. Equilibrium solubility of CN was determined in a range of anhydrous and diluted lipid-based formulations. Dynamic dispersion tests were carried out to investigate the efficiency of drug release and magnitude of precipitation that could occur upon aqueous dilution. Droplet sizes of selected formulations, upon (1:1,000) aqueous dilution, were presented. The optimal formulations were enrolled in subsequent dissolution studies. The results showed that increasing lipid chain length and surfactant lipophilicity raised the formulation solvent capacity, while adding co-solvents provoked a negative influence. The inclusion of mixed glycerides and/or hydrophilic surfactants improved the drug release efficiency. Generally, no significant precipitation was observed upon aqueous dilution of the formulations. Five formulations were optimal in terms of their superior self-emulsifying efficiency, drug solubility, dispersion characteristics, and lower droplet size. Furthermore, the optimal formulations showed superior dissolution profile compared to the marketed (Stugeron®) tablet. Most importantly, they could resist the intensive precipitation observed with the marketed tablet upon shifting from acidic to alkaline media. However, SNEDDS containing medium-chain mixed glycerides showed the highest drug release rate and provide great potential to enhance the oral CN delivery. Accordingly, the lipid portion seems to be the most vital component in designing CN self-nanoemulsifying systems.

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Acknowledgments

The authors would like to acknowledge SABIC graduate student fund (number MED-30-44). The authors are grateful to Prof. Adel Sakr for his scientific support and professional management. In addition, the authors would like to thank Dr. Magdi Abdel-Hamid for his great efforts in the UPLC analysis.

Disclosures

The authors report no conflicts of interest in this work.

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Affiliations

  1. Kayyali Chair for Pharmaceutical Industries, Department of Pharmaceutics, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh, 11451, Kingdom of Saudi Arabia

    Ahmad Abdul-Wahhab Shahba, Kazi Mohsin & Fars Kaed Alanazi

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  1. Ahmad Abdul-Wahhab Shahba
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  2. Kazi Mohsin
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  3. Fars Kaed Alanazi
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Corresponding author

Correspondence to Kazi Mohsin.

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Shahba, A.AW., Mohsin, K. & Alanazi, F.K. Novel Self-Nanoemulsifying Drug Delivery Systems (SNEDDS) for Oral Delivery of Cinnarizine: Design, Optimization, and In-Vitro Assessment. AAPS PharmSciTech 13, 967–977 (2012). https://doi.org/10.1208/s12249-012-9821-4

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  • DOI: https://doi.org/10.1208/s12249-012-9821-4

Keywords

  • cinnarizine
  • lipid-based formulations
  • oral drug delivery
  • SNEDDS
  • solubility enhancement