AAPS PharmSciTech

, Volume 19, Issue 8, pp 3791–3808 | Cite as

Intranasal Surface-Modified Mosapride Citrate-Loaded Nanostructured Lipid Carriers (MOS-SMNLCs) for Treatment of Reflux Diseases: In vitro Optimization, Pharmacodynamics, and Pharmacokinetic Studies

  • Reham Waheed HammadEmail author
  • Rania Abdel Baset Sanad
  • Nevine Shawky Abdelmalk
  • Randa Latif Aziz
  • Faisal A. Torad
Research Article


Gastroesophageal reflux disease (GERD) is an esophageal injury occurred when the stomach contents reflux abnormally into the esophagus. GERD complications include esophageal adenocarcinoma. Mosapride (MOS) is a safe prokinetic agent potentially used to treat GERD. Yet, its low solubility and bioavailability due to extensive first-pass metabolism limits its applications. This study aimed to formulate MOS nanostructured lipid carriers (MOS-NLCs) via the intranasal route to improve its bioavailability. Melt–emulsification low temperature–solidification technique using 23 full factorial design was adopted to formulate MOS-NLCs. Eight formulae were prepared and assessed in terms of entrapment efficiency (%EE), particle size, and in vitro release. Glycerol addition significantly reduced the particle sizes and improved %EE and %drug released. Surface modification using chitosan was applied. The optimized MOS surface-modified nanostructured lipid carriers (MOS-SMNLCs-F7)(stearic acid, 4% glycerol, 0.5% LuterolF127, 0.5% chitosan) showed low particle size 413.8 nm ± 11.46 nm and high %EE 90.19% ± 0.06% and a threefold increase in permeation of MOS with respect to the drug suspension. MOS-SMNLCs (F7) was also evaluated for its bioavailability compared with drug suspension and commercial product. Statistical analysis revealed a significant increase in gastric emptying rate to be 21.54 ± 1.88 contractions/min compared with10.02 ± 0.62 contractions/min and 8.9 ± 0.72 contractions/min for drug suspension and oral marketed product respectively. Pharmacokinetic studies showed 2.44-fold rise in bioavailability as compared to MOS suspension and 4.54-fold as compared to the oral marketed product. In vitro/in vivo studies proven to level A correlation between in vitro permeation through sheep nasal mucosa and in vivo absorption. Therefore, MOS-SMNLCs could be considered a step forward towards enhancing the clinical efficacy of Mosapride.


Mosapride citrate surface-modified nanostructured lipid carriers intranasal administration in vitro permeation gastric emptying rate 



This work was supported by National Organization for Drug Control and Research, Egypt, and Faculty of Pharmacy, Cairo University, Egypt. The ultrasonography examination was conducted with the help of Dr. Mohamed El-said Associate lecturer, Department of Medicine and Infectious Diseases, Faculty of Veterinary Medicine, Cairo University.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflicts of interest.


The authors only are responsible for the content and writing of the article.

Supplementary material

12249_2018_1142_MOESM1_ESM.avi (8.2 mb)
ESM 1 (AVI 8447 kb)
12249_2018_1142_MOESM2_ESM.avi (3.2 mb)
ESM 2 (AVI 3320 kb)


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Copyright information

© American Association of Pharmaceutical Scientists 2018

Authors and Affiliations

  • Reham Waheed Hammad
    • 1
    Email author
  • Rania Abdel Baset Sanad
    • 1
  • Nevine Shawky Abdelmalk
    • 2
  • Randa Latif Aziz
    • 2
  • Faisal A. Torad
    • 3
  1. 1.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 Surgery, Anesthesiology and Radiology, Faculty of Veterinary MedicineCairo UniversityCairoEgypt

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